Induction of idiotope suppression in the anti-azophenylarsonate response of T-depleted A/J mice.

The homologous, monoclonal antiidiotope, MB, induced idiotope suppression that was remarkably stable and could be transferred by B lymphocytes. Marked depletion of T cell function, confirmed by limiting diluting analysis, did not affect the ability of MB to suppress the corresponding idiotope. Suppression induced by MB appears to result from direct interaction with idiotope-positive B cells, without the intervention of idiotope-specific T suppressor cells.

Surgical management of squamous cell carcinoma of the base of the tongue.

An 11-year experience with 100 patients who had surgery as definitive treatment for squamous cell carcinoma of the base of the tongue between 1979 and 1989 has been retrospectively reviewed. Although 81% of the patients had stage III or stage IV disease, mandible continuity was maintained in 86%, and the larynx was preserved in 80%. Lymphadenectomy was performed in conjunction with the primary resection in a total of 89 patients, including 62 patients who had clinically evident metastases. Postoperative radiation was administered to 63 patients because of positive resection margins (17), positive cervical lymph nodes (34), or high tumor stage (12). Overall and disease-specific 5-year survival rates for the entire group were 55% and 65%, respectively. The 5-year disease-specific survival rates for stages I/II, III, and IV were 77%, 64%, and 59%, respectively. Local control was achieved in all but 18 patients. Our results indicate that surgery remains a viable treatment option for patients with advanced base-of-tongue cancer. Prospective trials are necessary to compare surgery versus definitive radiotherapy with respect to patients' survival and quality of life.

Chronic pediatric stridor: etiology and outcome.

Stridor in children is usually acute. This paper represents a chart review and telephone survey of 60 patients with chronic pediatric stridor. The most common etiology was laryngomalacia, which required airway intervention in 22% of the patients. The symptoms persisted beyond 18 months of age in 17% of the patients. Twelve percent of the patients had multiple lesions; 65% of the second lesions were below the vocal cords. It appears that the presence of cyanosis should increase physician suspicion of multiple lesions. There was not a higher risk of recurrent upper respiratory infections with any of the diagnoses.

Adult supraglottitis.

Airway management of supraglottitis in the adult is controversial as regards the choice between observation and acute intervention. This study was undertaken to determine whether factors exist that place patients at higher risk of airway obstruction and to review conservative treatment outcome. Of 46 cases during an 8-year period, seven required tracheostomy and 39 were observed. Odynophagia and fever were present in all patients. Yearly clusters of up to six cases in 1 month were detected. White blood cell count and heart rate were significantly more elevated in those who underwent tracheostomy. A symptom duration of less than 24 hours was associated (p < 0.05, chi 2 analysis) with airway compromise as well. There was no associated morbidity or mortality, and mean hospital stay was 5.2 days for those observed and 7.9 days for those who underwent tracheostomy.

Homologous monoclonal antibodies induce idiotope-specific suppression in neonates through maternal influence and in adults exposed during fetal and neonatal life.

The fine specificity of idiotype suppression induced early in ontogeny was investigated in the murine A/J anti-azophenylarsonate (Ar) response. Suppression was induced with two hapten-inhibitable, homologous monoclonal anti-idiotopic antibodies, AI and MB, that recognize partially overlapping sets of Ar-immune antibodies. Suppression was found to be idiotope-specific when adult mice were exposed to anti-idiotope as neonates; suppression was also idiotope specific when adult mice were exposed to anti-idiotope during fetal (through maternal inoculation) and neonatal life. Of particular interest, anti-idiotope, administered maternally, induced suppression in offspring first immunized with Ar as neonates, and this suppression was idiotope specific too. Thus, AI and MB induce idiotope-specific suppression in mice exposed to anti-idiotope early in ontogeny. These results parallel previous findings in adult mice and suggest that the mechanism of suppression in very young mice is the same as that in adults.

5-epi-Sisomicin and 5-epi-Gentamicin B: substrates for aminoglycoside-modifying enzymes that retain activity against aminoglycoside-resistant bacteria.

A number of bacterial strains, each possessing a different aminoglycoside-modifying enzyme, were examined for susceptibility to sisomicin and gentamicin B and the semisynthetic derivatives 5-epi-sisomicin and 5-epi-gentamicin B. Although strains possessing AAC (6') or APH(3') enzymes were equally resistant to the 5-epi-compounds, those possessing AAC(3)-I, ANT(2"), or AAC(2') enzymes were much more sensitive to the 5-epi derivatives. Analysis of partially purified aminoglycoside-modifying enzymes from the strains showed that the 5-epi compounds were substrates even for those enzymes found in susceptible strains [AAC(3)-I, ANT(2"), and AAC(2')]. However, a more detailed study of the enzymes showed that they had much increased Km values for the 5-epi derivatives; the 5-epi compounds were much less effectively modified than the parent antibiotics. This confirms and extends the notion that enzymatic modification of aminoglycosides is not in itself sufficient to confer resistance to the drugs, but also that the modification must be efficient, as reflected in the Km values.

Selection of aminoglycoside-resistant variants of Pseudomonas aeruginosa in an in vivo model.

The therapeutic failure of aminoglycosides in leukopenic mice was studied. Pseudomonas aeruginosa isolated from experimentally infected leukopenic mice was analyzed for susceptibility to gentamicin. Bacterial population analyses were performed before, during, and after therapy with high doses of gentamicin. Inocula from numerous strains, including P. aeruginosa strain ATCC 27853, harbored slowly growing aminoglycoside-resistant subpopulations. In leukopenic mice (in contrast to normal mice) receiving gentamicin, the breakthrough growth of these subpopulations occurred 6 hr after treatment. Resistance to gentamicin reversed in vivo when gentamicin treatment was stopped. The emergence of gentamicin-resistant subpopulations was successfully suppressed by a combined treatment regimen of gentamicin and ticarcillin. Gentamicin-ticarcillin synergy in these infections is due, in part, to antimicrobial suppression of slowly growing aminoglycoside-resistant subpopulations of bacteria.

Impact of dosing intervals on activity of gentamicin and ticarcillin against Pseudomonas aeruginosa in granulocytopenic mice.

The influence of dosing intervals on the activity of gentamicin and ticarcillin against Pseudomonas aeruginosa was studied in vivo. Granulocytopenic mice infected with P. aeruginosa in the thigh muscle were treated with 1-hr or 3-hr injections of gentamicin, ticarcillin, or gentamicin-ticarcillin. Plasma pharmacokinetics of the drugs were correlated with antibacterial activity. Gentamicin injected every 1 hr tended to be less active than gentamicin injected at longer intervals. In contrast, ticarcillin given every 1 hr was significantly more efficacious than equivalent total doses injected every 3 hr. The dosing schedule of gentamicin-ticarcillin was again important for ticarcillin but did not appreciably affect the antibacterial activity of gentamicin. Thus, antimicrobial chemotherapy of P. aeruginosa infections in the granulocytopenic host might be improved by administering ticarcillin rather than gentamicin as a constant infusion.