Fifty-six patients with serologically confirmed bee sting hypersensitivity were treated for 1-3 years with either bee venom (BV) (31 patients) or wholebody extract (WBE) (25 per cent of re-exposed patients on BV-therapy showed a diminished reaction and 75% no reaction. Thirty-three per cent of re-exposed patients on WBE-therapy developed an unchanged or worse reaction, 42% a diminished reaction and 25% no reaction at all. An initial rise in BV-specific IgE was observed in BV-treated patients, whereas IgE levels after 1 year of treatment lay significantly below pretreatment values in both treatment groups. BV-specific IgG increased markedly in patients on BV-therapy and decreased slightly in those on WBE-therapy. The initial IgE increase induced by BV-therapy was insignificant in patients with high pretreatment levels of specific IgG-antibodies. Similarly, re-exposed patients with high BV-specific IgG showed no IgE increase, whereas a substantial rise in specific IgE was observed in those with low IgG. On the basis of clinical and serological results immunotherapy with BV is considered to be clearly superior to immunotherpy with WBE.

42 patients with confirmed hypersensitivity to honey bee (HBV) and/or yellow jacket (YJV) were treated with the respective venoms (7 with HBV, 5 with VJV and 30 with both venoms). Treatment tolerance, skin tests (ST), specific IgE- and specific IgG-antibodies were monitored before, after 3, 6, 12, 24 and 36 months. 21 patients had a rush and 21 a conventional treatment schedule. Maintenance dose was 100 micrograms. Adverse effects occurred as large local (8 patients), slight systemic (12 patients) and moderate to severe systemic reactions (4 patients). Of 24 re-exposed patients 17 had no reaction at all, six a markedly decreased and one an unchanged reaction. After 3 years of treatment ST became negative in nine of 31 patients on HBV and in seven of 26 patients on YJV. RAST became negative in three of 30 patients on HBV and 17 of 29 patients on YJV treatment. Both ST and RAST became negative in five HBV- and 10 YJV-treated patients. Loss of venom hypersensitivity according to diagnostic tests may correspond to actual desensitization and enable discontinuation of immunotherapy.

A once-daily dosing regimen for aminoglycosides is less expensive, at least as effective and possibly less toxic than multiple-daily dosing regimens. Once-daily dosing might also allow the frequency of measuring the serum concentrations of these antibiotics to be reduced since two of the major objectives of monitoring, high peak and low trough concentrations, are more likely to be achieved with this regimen. A novel strategy for monitoring serum concentrations which relies on a single sample obtained 8 h after a dose, as opposed to both trough and peak samples, is evaluated here. Serum kinetics of netilmicin were studied prospecu'vely in 51 adult patients with initial serum creatinine concentrations of < 130 /imol/L who were treated with a median daily dosage of 400 mg. Concentrations measured 8 h after administration were within the target range of 1-5-6 mg/L in 113 of 134 dosing intervals studied. Concentrations above and below this range correlated significantly with higher and lower 24-h trough concentrations and areas under the curve respectively. There was also a significant correlation between 8-h netilmicin concentrations and nephrotoxicity (P < 0-05); a relative increase of ^ 25% in the serum creatinine concentration or an absolute increase of > 25 //mol/L was detected in 0 of 7 patients with an 8-h concentration of < 1-5 mg/L, in 3 of 33 patients (91%) with an 8-h concentration of 1-5-6 mg/L and in 4 of 11 patients (36%) with an 8-h concentration of > 6 mg/L. The results of this study suggest that adequate information about serum netilmicin concentrations in patients receiving a once-daily dose may be derived from a sample obtained 8 h after administration.

The effect of dosing regimen on nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics was studied in a prospective, randomised clinical study. Therapy was started with total daily doses of 6 mg/kg given once (od) or thrice (tid) daily to 56 and 57 patients, respectively. Subsequent doses were adjusted according to serum levels. No major differences in toxicity or efficacy were noticed between od and tid regimens: clinical failures occurred in two and two patients, four and five patients suffered from a decrease of ^ 20 dB at least unilaterally at one frequency between 8 and 18 kHz, six and seven patients had a >25 /jmol/L or >25% increase in serum creatinine, respectively. Serum creatinine or creatinine clearance did not change significantly during either therapy. Major differences between the two study groups were limited to pharmacokinetic parameters. Od dosing resulted in higher peak (mean of 21.6 vs 7.2 mg/L) and lower trough levels (0.5 vs 1.4mg/L).