A rat model of otitis media with effusion caused by eustachian tube obstruction with and without Streptococcus pneumoniae infection: methods and disease course.

OBJECTIVE: To describe the clinical and histopathologic progression of a rat model of otitis media with effusion caused by eustachian tube obstruction (ETO) with and without Streptococcus pneumoniae infection. METHODS: In 164 rats, the left, bony eustachian tube was approached via a ventral incision and obstructed with dental material. Then 108 rats were infected via an intrabullar injection with S pneumoniae. At 48 hours, the infected rats were treated for 5 days with ampicillin. All ears were evaluated by weekly otomicroscopy. On each of days 1, 2, 7, 21, 35, 56, and 112, four rats were killed for histologic study. All effusions were cultured for bacteria. RESULTS: Fourteen rats died of surgical complications; effusion resolved by 2 weeks in 9 rats. During the first few days, infected ears with ETO had bulging tympanic membranes, followed by tympanic membrane retraction, purulent effusion, and otorrhea (50%) over the next few weeks, whereas uninfected ears with ETO developed retraction and serous effusion during the same time frame. At later times, all ears with ETO presented with retraction and serous or serous-mucoid effusion. S pneumoniae was recovered only from the infected ears with ETO (days 1 and 2), with some colonization by nonpathogenic microorganisms observed equally in both groups of ears. Histology showed a typical acute inflammatory reaction in the challenged ears with ETO through day 14 and then a chronic inflammation for all ears with ETO. CONCLUSION: The experimental methods provoked reproducible pathologic signs similar to those for otitis media with effusion. Given the availability of rat-specific reagents, this model is well suited for studies of cytokine elaboration during disease pathogenesis.     

Inversion of the Bohr effect upon oxygen binding to 24-meric tarantula hemocyanin.

The Bohr effect describes the usually negative coupling between the binding of oxygen and the binding of protons to respiratory proteins. It was first described for hemoglobin and provides for an optimal oxygen supply of the organism under changing physiological conditions. Our measurements of both oxygen and proton binding to the 24-meric tarantula hemocyanin establish the unusual case where a respiratory protein binds protons at low degrees of oxygenation but releases protons at high degrees of oxygenation. In contrast to what is observed with hemoglobin and other respiratory proteins, this phenomenon amounts to the inversion of the Bohr effect in the course of an oxygen-binding curve at a given pH value. Therefore, protons in spider blood can act either as allosteric activators or as allosteric inhibitors of oxygen binding, depending on the degree of oxygenation of hemocyanin. These functional properties of tarantula hemocyanin, which cannot be explained by classical allosteric models, require at least four different conformational states of the subunits. Inspection of the known x-ray structures of closely related hemocyanins suggests that salt bridges between completely conserved histidine and glutamate residues located at particular intersubunit interfaces are responsible for the observed phenomena.     

Metabolic products of microorganisms. 255. Nikkomycins Wz and Wx, new chitin synthetase inhibitors from Streptomyces tendae

Two new dipeptidyl nikkomycins of the Z and X type were isolated from the culture broth of Streptomyces tendae TU 901/395-11/32 and characterized. They show a variation in the amino acid moiety of the molecule. Nikkomycin Wz is composed of L-tyrosine and 5-amino-5-deoxy-D-allo-furanuronic acid N-glycosidally bound to uracil, whereas nikkomycin Wx is composed of L-tyrosine and 5-amino-5-deoxy-D-allo-furanuronic acid N-glycosidally bound to 4-formyl-4-imidazolin-2-one. The new nikkomycins are good inhibitors of chitin synthetase from Coprinus cinereus but they did not inhibit growth of fungi and yeasts.     

Results of a double blind study of 89-strontium therapy of skeletal metastases of prostatic carcinoma

Forty-nine patients were treated with either 3×75 MBq ⁸⁹Sr or saline as placebo. Analysis of results 1 to 3 years after therapy revealed the ineffectiveness of ⁸⁹Sr to relieve pain from metastases. Unexpectedly, a higher survival rate was found after Sr application (46% vs 4% after 2 years). Covariate analysis underlines the effect of ⁸⁹Sr therapy on life expectation.     

Inter- and intraobserver variability in the histopathological diagnosis of medullary carcinoma of the breast,and its prognostic implications

Summary One hundred thirty-one breast carcinomas with medullary features, registered in the Danish Breast Cancer Cooperative Group from 1977–1982, have been histopathologically reviewed by two senior pathologists and classified as typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), and non-medullary carcinoma (NMC). Diagnostic criteria were based on those put forward by Ridolfiet al. and Fisheret al. The procedure was repeated with an interval of about one year by both pathologists. The diagnostic interobserver agreement was 72% with a Kappa of 0.55. The intraobserver agreement was 77% and 63% with Kappa values of 0.64 and 0.44, respectively. To see whether the observed inter- and intraobserver variability had any prognostic implications, diagnostic subgroups for both pathologists were analyzed with Kaplan Meier plots for recurrence-free survival (RFS) and with log rank tests. In the first evaluation pathologist 1 segregated a group of TMC with a significantly better RFS than for the NMC group, and pathologist 2 segregated a group of TMC with a corresponding strong trend. These findings could not, however, be reproduced in the second evaluation. The study indicates that the criteria of TMC and AMC as proposed by Ridolfiet al. need to be sharpened and simplified in order to reduce inter-and intraobserver variability. Larger studies with a control group of infiltrating ductal carcinomas are mandatory to elucidate the clinical importance of the diagnoses of Typical and Atypical Medullary Carcinoma of the breast.     

Effects of alkyl chain length on the inhibition of NNK-induced lung neoplasia in A/J mice by arylalkyl isothiocyanates

Six homologous arylalkyl isothiocyanates were evaluated fortheir abilities to inhibit pulmonary adenomas induced by thetobacco-specific nitrosamine 4-(methylnitrosamino)-l-(3-pyridyl)-1-butanone(NNK) in A/J mice. Four consecutive daily doses (5 µmol/mouse)of phenyl isothiocyanate (PITC), benzyl isothiocyanate (BITC),phenethyl isothiocyanate (PETTC), 3-phenylpropyl isothiocyanate(PPITC), 4-phenylbutyl isothiocyanate (PBITC), 4-oxo-4-(3-pyridyl)-butylisothiocyanate (OPBITC) and corn ofl were administered to miceby gavage. Two hours following the final dosing, mice were administeredsaline or 10 µmol of NNK in saline i.p. Pulmonary adenomaswere counted at 16 weeks after NNK administration. The miceadministered only corn oil prior to NNK developed an averagemultiplicity of 9.2 tumors/ mouse. Pretreatment with PITC, BITCand OPBITC had no significant effects on NNK-induced lung neoplasia.However, PEITC pretreatment resulted in a 64% reduction of lungtumor multiplicity, but did not affect the percentage of micethat developed tumors. Both PPITC and PBITC decreased tumormultiplicity by 96% and the percentage of tumor-bearing animalsby >60%. These results, in conjunction with our previouswork, demonstrate a general trend of increasing inhibition ofNNK-induced lung neoplasia by arylalkyl isothiocyanates withincreasing alkyl chain length. This study also demonstratesthe remarkable inhibitory activities of PPITC and PBITC, twoisothiocyanates that had not previously been tested as chemopreventiveagents.     

Tension fixation of rupture of the symphysis with woven polydioxanone sutures

In seven patients (mean age 22 years) with injuries of the pelvic ring, the rupture of the symphysis was treated by polydioxanone ligaments. Complete rupture of the ileosacral joint was treated twice by additional external fixation, twice a compression screw osteosynthesis was applied. Incomplete iliosacral rupture in another three cases was not operated. Patients were treated functionally without signs of loosening or instability. After a control examination after 5 months all patients were free of symptoms in the area of the symphysis. Infection of the operation area did not accur. In our opinion the advantages of this method are simple operative technique, reduced risk of infection and no need for removal of metallic implants. Our excellent initial experience with synthetic PDS ligaments in operative treatment of symphysis ruptur seem to justify its application for other injuries like iliosacral or acromioclavicular rupture.