Data on 87 patients (113 ears) with chronic secretory otitis media (SOM) are reported. The bacteriological analysis of the middle ear fluid (MEF) revealed Streptococcus pneumoniae in 7% of ears, Hemophilus influenzae in 9%, opportunistic bacteria in 20%, while 64% of the samples showed no growth. Free capsular polysaccharide pneumococcal antigens were found in 5% of the MEF samples using counterimmunoelectrophoresis (CIEP) with Omniserum containing 83 different pneumococcal polysaccharide types. Heating of the samples to disrupt the immune complexes increased the frequency of positive samples to 27%. These findings, together with the frequent occurrence of S pneumoniae and H influenzae in the nasopharynx, strongly support the opinion that chronic SOM in a considerable number of cases is an immune complex disease.

Specimens of middle ear effusion and adenoid tissue were studied for bacteria and pneumococcal capsular antigen in 107 patients with secretory otitis media. 120 of 163 middle ear effusion samples (73.6%) were negative on bacterial culture. Hemophilus influenzae was present in 9.2% and Streptococcus pneumoniae in 1.8%. Hemophilus influenzae was cultured from 44.8% and Streptococcus pneumoniae from 35.5% of 107 adenoid tissue specimens. Free pneumococcal capsular antigen was demonstrated in 10.4% of the middle ear fluids and this figure rose to 23% when antigen was liberated from the immune complexes by heating. The corresponding figures for adenoid tissue suspension were 27.1% and 39%. The adenoid tissue or the lymphoid tissue of the entire oropharynx could act as the source of antigen which could maintain immune complex disease in some patients suffering from secretory otitis media.

Human T-lymphocyte preparations from peripheral blood with either high- or low-avidity receptors for wheat germ agglutinin (WGA) were obtained by fractioned on WGA--Sepharose columns. Both fractions contained progenitors of alloreactive T cells, proliferating in mixed lymphocyte culture (MLC) and acting as effector cells in cell-mediated lympholysis (CML). Proliferation and CML activity of the two fractions were equal and similar to those of the unfractionated cells. However, when the lymphocytes were fractionated after 5 days' MLC, most of the proliferating and cytolytic cells were found in the lymphocyte fraction enriched in cells with high-avidity receptors for WGA. The reactivity of the fractions was correlated to their content of blast-transformed cells. The binding of MLC-activated lymphocytes to WGA was specific, since it was inhibited by the competitive hapten D-GlcNAc and no cells were retained on control columns charged with human serum albumin-Sepharose. B cells and monocytic cells were enriched in the fraction with low-avidity receptors for WGA. As indicated by experiments in which cells were mixed in different proportions, the low MLC-CML activity of the lymphocytes in the fraction with low-avidity WGA receptors was not caused by suppressor cells present in that fraction.

Seventy-eight patients with secretory otitis media were given erythromycin ethylsuccinate 50 mg/kg/day, divided into 2 doses, for 7-8 days before undergoing adenoidectomy and tympanostomy. Nasopharyngeal swabs for bacterial culture were obtained before medication and at surgery and the adenoid homogenate was also studied for bacteria. Pneumococci and Branhamella strains became significantly reduced, while Hemophilus influenzae showed no change. Pneumococcus and Branhamella strains partially returned one month after surgery and in part were found in patients who had not had these strains before antimicrobial therapy. Erythromycin ethylsuccinate can sterilize neither the adenoids nor the middle ear space if the causative agent is Hemophilus influenzae.

Concentrations of sulfadiazine were compared with those of sulfamethoxazole after combination treatment of sulfonamide plus trimethoprim. Sulfadiazine was used in doses of 1.6, 1.0 or 0.6 g ini, and thereafter half of the initial dose twice daily. The initial dose of sulfamethoxazole was 1.6 g and the subsequent doses 0.8 g twice daily. All of these preparations contained the same amount of trimethoprim, 320 mg initially and then 160 mg twice daily. In plasma the free minimum concentrations of sulfadiazine were more than 10 mg/l even after the lowest dose, and both after the initial dose and after subsequent doses. Because of the more favorable MIC of sulfadiazine, these are more effective free concentrations than those obtained after conventional doses of sulfisoxazole. The free minimum concentrations of sulfamethoxazole were over 15 mg/l, which were approximately the same as those after the highest dose of sulfadiazine. In urine the free effective concentrations after sulfamethoxazole and even the lowest dose of sulfadiazine were well over 100 mg/l. The apparent half-lives of sulfamethoxazole and sulfadiazine were 13.4 ± 2.8 h and 14.9 ± 8.7 h, respectively. The minimum concentrations of trimethroprim were higher than 1 mg/l on an average. There were no differences between different combinations in this respect. It is concluded that on the pharmacokinetic basis, sulfadiazine appears to be as good a choice for combinations with trimethoprim as is sulfamethoxazole. Theoretically, it is effective at the same dosage level as sulfamethoxazole. This is due to its favorable pharmacokinetic properties, namely low protein-binding and relatively low degree of metabolism. As compared with sulfisoxazole, both of these sulfonamides are overdosed, and clinical trials by using a lower dosage appear feasible.