No abstract

Eight patients treated with a total of 220-550 million U penicillin-G developed neutropenia. These cases have been compared with eight patients receiving a similar dose of pencillin-G with no adverse reactions and with eight untreated subjects. All penicillin-treated patients showed raised levels of anti-IgG antibodies and lymphocyte culture stimulation indices. These values were highest in the neutropenia group. Both of the two tests significantly discriminated the three groups. Antineutrophil antibodies could be detected in four of seven neutropenic patients with a staphylococcal-slide-assay while indirect immunofluorescence and microcytotoxicity tests failed to reveal these antibodies. The literature dealing with neutropenias induced by penicillin-G and its congeners is reviewed. We conclude that (1) penicillin-G in doses exceeding a total of 200 million U frequently induces neutropenia, (2) an immune-mediated pathogenesis a highly probable, (3) neutropenia after penicillins is different from two hither-to accepted types of this side effect, (4) sufficiently high amounts of penicillin-G intravenously always induce sensitization against this drug.

We have recently shown that high-dose intravenous therapy with penicillin-G always results in both sensitised lymphocytes and rise of anti-penicilloyl IgG antibodies. If penicillin-G is strictly given as freshly prepared bolus doses this sensitisation is prevented. In 193 patients, intravenous treatment with penicillin-G without special precautions (bolus doses stored up to 36 h at 4 degrees C or continuous infusions) led to 8.3% definite, 6.7% probable and 14.0% possible adverse reactions. In 116 patients treated exclusively with freshly dissolved doses, 0.9% definite, 1.7% probable and 4.3% possible reactions occurred. Whereas haemolytic anaemia (7) and neutropenia (12) were observed in 19 cases of the first group no such reactions were seen in the second group. Strict application of freshly prepared single doses prevents the majority of adverse reactions following highdose intravenous penicillin-G therapy. Degradation and transformation products formed in vitro are therefore the causative agents rather than the penicillin molecule itself.

Sera from 125 patients receiving mean total doses of β-lactam therapy of 215 g over a mean of 14 days were assayed by radioimmunoassay. Titres of anti-penicilloyl antibodies, expressed in arbitrary units of specific IgG per microlitre of serum (u/μl), ranged from undetectable (<3 u/μl) to 1,650 u/μl. There was a higher prevalence of elevated IgG levels in patients who developed haemolytic anaemia or neutropenia compared with patients with no adverse reactions but only in those patients who developed haemolytic anaemia were the antibody titres significantly higher. A subsidiary finding was that a correlation was established between mean total dose and prevalence of positive IgG titres, on a patient group basis (r = 0.87).

The interaction of oxytocin with bovine neurophysin II in 0.1 M-sodium phosphate, pH 5.8, was investigated by equilibrium-dialysis and sedimentation studies. Sigmoidality of the binding curve is attributed to isomerization, either hormone-induced or pre-existing, with preferential binding of oxytocin to one isomeric state. Results are consistent with a binding equation of the form r = (2P[S]+2PQ[S]2)/(1+2P[S]+PQ[S]2) and values of 0.7 X 10(5)M-1 and 1.3 X 10(5)M-1 for P and Q respectively. The significance of these two parameters in relation to current theories of allostery is also discussed.