Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

A preliminary cost effectiveness analysis of an intervention to reduce homelessness among the mentally ill

The Critical Time Intervention Project is a three-year clinical trial which tests a time-limited, supportive intervention to reduce recurrent homelessness among mentally ill men moving from a shelter to the community. Along with a comparison of nights spent homeless and other outcomes, the evaluation of the Critical Time Intervention includes a comparison of the relative costs of the intervention, compared to usual treatment. Such cost effectiveness analyses are difficult to perform and are rarely applied to mental health treatments. This paper presents the general scheme of this analysis and discusses critical issues in the construction and measurement of cost variables. Preliminary results which have implications for the cost analysis are presented.     

Polymorphism and drug-selected mutations in the protease gene of human immunodeficiency virus type 2 from patients living in Southern France

The susceptibility of human immunodeficiency virus type 2 (HIV-2) to protease inhibitors (PI) is largely unknown. We studied HIV-2 protease genes from 21 HIV-2-infected patients who were exposed or not exposed to PI. The aim of this study was (i). to characterize the polymorphism of HIV-2 protease in the absence of drug, (ii). to know whether the HIV-2 protease gene naturally harbors HIV-1 drug resistance codons, and (iii). to identify mutations emerging under PI-selective pressure. Sixty-five HIV-2 RNA or proviral DNA samples were directly sequenced from the plasma or peripheral blood mononuclear cells of 8 patients who had received PI and 13 patients who had never received any antiretroviral. In untreated patients, the highest amino acid variability in HIV-2 protease was observed at positions 14, 40, 43, 46, 65 and 70, and seven codons (10V, 32I, 36I, 46I, 47V, 71V, and 73A) associated with drug resistance in HIV-1 were highly prevalent. In addition, at six positions (positions 7, 46, 62, 71, 90, and 99), the amino acid variability or the amino acid frequencies or both differed significantly in PI-treated and untreated patients, suggesting that mutations 7K-->R, 46V-->I, 62V-->A/T, 71V-->I, 90L-->M and 99L-->F were occurring under PI-selective pressure. At these positions, at least one sample simultaneously harbored both wild-type and mutated codons, while substitutions at positions 62, 71, 90, and 99 were confirmed in a longitudinal analysis. Moreover, the presence of codons 46I and 99F in the absence of drug in HIV-2 subtype B proteases may reflect natural resistance to PI. In conclusion, the present study revealed that HIV-2 strains harbor specific patterns of natural polymorphism and resistance.     

Semiautomated determination of minimum bactericidal concentrations of antibiotics

Using a newly devised 50-channel photometer which records the opacity of growing bacterial cultures, it was shown that the time taken by cultures diluted 1/1000 in fresh broth to reach 50% of the opacity of a fully grown culture was inversely related to the concentration of organisms in the original culture. This relation was used to determine the numbers of survivors after exposure to benzylpenicillin and gentamicin alone and in combination. The procedure is commended as a labour-saving and potentially rapid method of obtaining comprehensive information on the bactericidal action and interaction of antibiotics.