The value of politzerization in the treatment of atelectatic ears

The value of Politzerization as a method of treatment in atelectatic ears and secretory otitis media is controversial. In some places it has been used routinely for decades, in others it has been almost forgotten. A quantitative study of its therapeutic value has been difficult to find. The present study is an attempt to evaluate the therapeutic value of such an 'air douche' in atelectatic ears. Thirteen middle ears with atelectasis were Politzerized daily with air or N2 for up to five consecutive days. Once Politzerized, the atelectasis and retraction pockets disappeared in all the ears examined. However, continuous observation of the Politzerized ears with the surgical microscope revealed that all the ear drums returned swiftly to their retracted position. The time it took for a drum to return to its original place varied from 15 minutes up to a maximum of 335 minutes. Our observations show that even an increased number of Politzerizations did not alter the speed of reappearance of the atelectasis. It would therefore seem that the therapeutic value of Politzerization in atelectatic ears is doubtful.     

Gas diffusion in the middle ear

The ex vacuo theory, claiming that in cases of middle ear underaeration air enters the middle ear through the Eustachian tube in diminished amounts while oxygen continues to leave it into the blood by diffusion as in normal condition, does not provide a complete explanation for the aeration problems encountered in middle ear pathology. This study shows that when atelectatic ears are politzerized (hyperinflated) with different gases, these gases disappear with a speed that correspond to the diffusion coefficient of the different gases. This finding together with the fact that the composition of middle ear gases is very similar to that found in the venous circulation suggests that it is a diffusional process of several gases from the middle ear into the blood and in the opposite direction that mainly determines the middle ear pressure.     

Structure-based Search for Peptide Ligands that Cross-react with Melanocortin Receptors

Purpose. To define sequence motifs that can be used to identify peptide ligands of the melanocortin receptor (MCR). Methods. Screening of combinatorial libraries has led to identification of D-Trp-Nle-NH₂ (Nle, norleucine) and D-Trp-Arg-NH₂ as the smallest structures known to antagonize the amphibian MCR (1). As the basis of a search paradigm, peptide-ligands containing these or similar motifs within their larger primary structure were examined for ability to antagonize amphibian and recombinant human MCRs. Compounds examined include analogs of substance P, leutinizing-hormone releasing-hormone, endothelin, neurotensin, and opioid-somatostatin. Results. Of seven compounds tested containing the predetermined search motif D-Trp-AA_x (where AA_x is Arg, Leu, Nle, or Ile), six were found to have previously unrecognized antagonist activity at the amphibian MCR (K _d 30 to 5000 nM). In contrast, of 14 similar control peptides lacking the D-Trp-AA_x search motif, only somatostatin displayed measurable antagonist potency. The anticancer peptide, [Arg⁸, D-Trp^7,9, N-methyl-Phe⁸]-substance P, was the most potent of the motif-containing peptides with a K _d of 31 nM. The µ-opioid antagonist D-Phecyclic[Cys-Tyr-D-Trp-Arg-Thr-Pen]-Thr-NH₂ (CTAP) also blocked the amphibian MCR (K _d 1 µM), but the related µ-antagonist CTOP, different only by only by substitution of Arg with ornithine within the search motif, was found to agonize the amphibian MCR (EC₅₀ 67 nM). CTAP and the anticancer peptide were also tested on human MCRs (hMCRs); while CTAP competed with -MSH at the hMC1 receptor, the anticancer peptide had no effect or was slightly stimulatory. Conclusions. We have identified dipeptide motifs that help distinguish antagonist ligands of the amphibian MCR from ligands known to interact with other G-protein coupled receptors. This approach might be generally applicable if motifs can identified for other receptors and their subtypes. In studies employing CTAP and CTOP, analogs previously considered highly selective for the µ-opioid receptor, cross-reaction with MCRs must be considered.     

Treatment of cholesteatoma and retraction pockets

Summary Treatment of retraction pockets (RP) and cholesteatomas depends on their nature and evolvement and the size of mastoid pneumatization. RP are secondary to vacillating middle ear negative pressure. Treatment when necessary consists of placing a ventilating tube, excision of the RP or both. In most children and adults, cholesteatoma is derived from RP (or atelectasis) of the tympanic membrane, where it can be termed retraction pocket cholesteatoma or secondary cholesteatoma. This type of cholesteatoma is associated with a non-pneumatized mastoid coupled by negative pressure. Approximately one-third of children's cholesteatomas present clinically behind an intact drum despite a pneumatized mastoid. Pathogenetically this type may be congenital or metaplastic and should be best termed primary cholesteatoma. Central perforations associated with cholesteatoma are probably derived from continuous tympanic membrane destruction by infection in cases of RP cholesteatomas or due to a primary cholesteatoma bursting out from the tympanic cavity. Canal-up surgery of cholesteatoma fails in 60% of cases at Tel Aviv University because of the inherent tendency of the tympanic membrane to retract once again. Residual disease was found in our cases to be a lesser cause for failure. Treatment depends on the type of cholesteatoma, emphasizing small radicals in sclerotic mastoids. When a pneumatized mastoid is encountered, a posterior tympanotomy should be considered.Presented at the Fourth International Conference on Cholesteatoma and Mastoid Surgery, Nigata, Japan; September 1992     

Morphine Impurity with Opioid Activity Is Identified as 10α-Hydroxymorphine

Pharmaceutical Research -     

Red Cell Distribution Width Can Predict the Significance of Angiographically Intermediate Coronary Lesions

Objective

In the present study, the association between red cell distribution width (RDW) with functional significance of intermediate coronary artery lesions was investigated.

Materials and Methods

Two hundred and forty-six consecutive patients, 168 males and 78 females, who underwent fractional flow reserve (FFR) measurement for angiographically intermediate coronary stenosis (40-70% in quantitative coronary analysis) in the left anterior descending coronary artery were enrolled into the study. The functional significance of intermediate coronary artery lesions was determined by FFR measurement. An FFR value <0.75 was defined as functionally significant. Venous blood samples were taken within 48 h before the FFR measurement, and RDW levels were determined by a Coulter LH Series hematology analyzer. Logistic regression analysis was used to examine the association between functional significance in FFR measurement and other variables.

Results

Of the 246 patients, 62 (25.2%) exhibited significant functional stenosis (FFR <0.75) in the FFR measurement. The mean RDW level was significantly higher in patients with significant stenosis (14.19 ± 0.73 vs. 13.69 ± 0.77, p < 0.001). In stepwise multivariate logistic regression analysis, RDW (OR = 2.489, 95% CI = 1.631-3.799, p < 0.001) and male gender (OR = 2.826, 95% CI = 1.347-5.928, p = 0.006) were independent predictors of significant functional stenosis.

Conclusion

Increased RDW levels were associated with functional significance of angiographically intermediate coronary artery stenoses.Key Words: Coronary artery stenosis, Fractional flow reserve, Erythrocyte indices, Red cell distribution width     

Aesthetic correction of isolated congenital absence of nasal lower lateral cartilages

Isolated congenital nasal anomalies that cause remarkable aesthetic deformities are extremely rare, and only a few cases have been reported in the literature. In this study, we present the case of a patient with nonsyndromic congenital isolated absence of the nasal lower lateral cartilage and the subsequent esthetic surgical correction. A satisfactory result was achieved. Level of Evidence: Level V, therapeutic study.     

Radioembolization with yttrium-90 resin microspheres for neuroendocrine tumor liver metastases

PURPOSE

We aimed to evaluate the effectiveness and safety of radioembolization with yttrium-90 (⁹⁰Y) microspheres in cases with unresectable neuroendocrine tumor liver metastases (NETLMs).

METHODS

Thirty patients (mean age, 55 years) underwent resin-based ⁹⁰Y radioembolization for unresectable NETLM at a single institution between April 2008 and June 2013. Post-treatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST). Prognostic variables that affected survival were determined.

RESULTS

The mean follow-up was 23.0±19.4 months and the median overall survival was 39 months (95% CI, 12.6–65.4 months), with one- and two-year survival rates of 71% and 45%, respectively. Imaging follow-up using RECIST at three-month intervals demonstrated partial response in 43%, complete remission in 3%, stable disease in 37%, and progressive disease in 17% of patients. Extent of tumor involvement was found to have a statistically significant influence on overall survival (P = 0.03). The existence of extrahepatic disease at the time of radioembolization, radiographic response, age, and primary neuroendocrine tumor site were not significant prognostic factors.

CONCLUSION

The current study demonstrates the effectiveness and safety of radioembolization for the treatment of unresectable NETLMs. We identified that the extent of tumor involvement has a significant effect on overall survival. The use of imaging methods reflecting metabolic activity or cellularity such as scintigraphy or diffusion-weighted MRI would be more appropriate, for the response evaluation of liver metastases after radioembolization.Neuroendocrine tumors (NETs) are a heterogenous group of slow-growing and hormon-releasing malignant tumors. Even though primary NETs originate from a number of locations, 40%–70% of all carcinoids arise in the small intestine and appendix (1, 2). The most common site for metastasis is the liver. Neuroendocrine tumor liver metastasis (NETLM) results in hormone-secretion-related symptoms leading to carcinoid syndrome, pressure on structures, or liver replacement (1–4). Patients with liver metastasis have a five-year survival rate of less than 20% (5). Over the years, improvements in local treatments yielded better control of the symptoms and survival rates, yet only 10% of the patients have limited illness and are eligible for surgery (6). Patient symptomatology and survival can be improved by transarterial treatments like embolization and chemoembolization (6). Limitations of these techniques include the short duration of the effects and the controversial approaches regarding the optimal timing and sequence of the procedures due to the variability of tumor progression (7, 8). Long-term survival benefit was not achieved with systemic chemotherapy (9–11) and treatment with somatostatin analogues is mostly associated with symptomatic relief; there is no clear knowledge of their effect on survival of patients who have carcinoid tumor and metastasis (12).Selective internal radiation therapy (SIRT) has been used to treat unresectable primary and secondary liver cancers for over a decade. Yttrium-90 (⁹⁰Y) is a pure high-energy β emitter with a mean tissue penetration of 2.5 mm. The radioactive microspheres prefer tumoral vascular distribution, so that normal liver tissue is relatively spared and high doses are directed to the tumoral tissue (13). Also, radioembolization-related acute and subacute toxicities are seemingly more tolerable than the ones related to other hepatic embolization procedures (14–16). In this study, we aimed to evaluate the effectiveness and safety of ⁹⁰Y microspheres in cases with unresectable NETLMs.