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The GABA(A) receptor is an important target for a variety of general anesthetics (Franks and Lieb, 1994) and for benzodiazepines such as diazepam. Specific point mutations in the GABA(A) receptor selectively abolish regulation by benzodiazepines (Rudolph et al., 1999; McKernan et al., 2000) and by anesthetic ethers (Mihic et al., 1997; Krasowski et al., 1998; Koltchine et al., 1999), suggesting the existence of discrete binding sites on the GABA(A) receptor for these drugs. Using anesthetics of different molecular size (isoflurane > halothane > chloroform) together with complementary mutagenesis of specific amino acid side chains, we estimate the volume of a proposed anesthetic binding site as between 250 and 370 A(3). The results of the "cutoff" analysis suggest a common site of action for the anesthetics isoflurane, halothane, and chloroform on the GABA(A) receptor. Moreover, the data support a crucial role for Leu232, Ser270, and Ala291 in the alpha subunit in defining the boundaries of an amphipathic cavity, which can accommodate a variety of small general anesthetic molecules.

Data from 1271 patients with perennial rhinitis has been assessed. This condition predominantly affects children and young adults; 31-5% stated that symptoms first appeared before the age of 10 years, less than 10% were aged 50 years or more suggesting that the disease process may well disappear in later life.The total sample size was equally divided between the sexes and the mean age for the sexes was similar. In terms of age distribution a sex difference was found in that the peak incidence for males occurred in the age group 10-19 years whereas for females it was in the third decade (P<0 001).The duration of the disease was, in most cases, between 2 and 9 years but it can extend to over 15 years and thus become subacute or chronic. The major symptom is blocking which could be due to either bistological changes in the mucosa or immunological reactions.Skin tests showed that 64% had a positive reaction to common allergens; however, nasal challenge tests were of little value in determining whether a patient could be classified as allergic. Eosinophils were noted in 66%. The value of skin tests and nasal smears is discussed.

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