Otitis media with effusion and S-carboxymethylcysteine and/or its lysine salt: a critical overview.

An overview of the placebo-comparative articles retrieved by a literature search on Medline - Embase - Biosis data banks from 1972 to 1993 was performed to evaluate the therapeutic relevance of the medical treatment with S-carboxymethylcysteine (SCMC) and its monohydrate lysine salt (SCMC-LYS) in patients with otitis media with effusion (OME). Ten original published studies were reviewed by an independent physician who assessed their quality by standard nine-items methodology. A meta-analytical approach was used to compare outcomes across all qualifying studies. Because of the heterogeneity of clinical endpoints, a new outcome measure was defined, i.e. overall clinical improvement, which consisted of the number of patients with complete resolution of clinical signs and symptoms and no need for surgical intervention. The objective evaluation criteria of normalisation of tympanogram was an additional end-point. Potential confounding variables such as eligibility criteria, treatment protocol and study design of the six methodologically complying studies were statistically homogeneous. No association was found between treatment effect-size and publication date or patients' age. Outpatients with disease duration of < 6 months, not previously treated, with bilateral ear involvement were included in the studies; half of them presented hyperplasia or hypertrophy of the pharyngeal or the adenoid tissue. Out of 483 patients, 430 (89%) terminated studies and were evaluable. Results from this meta-analysis indicate that patients with OME receiving oral SCMC/-lys benefit from the medical treatment to the extent of avoiding surgical intervention approximately 2.31 times more often than similar patients receiving placebo (ratio of active drug to placebo-effect on overall clinical improvement: 2.31; C.I. 1.28-4.20, P < 0.01) and attain reversion to normal of the tympanogram at an extent close to statistical significance (odds ratio: 2.25, C.I. 0.97-5.22, P = 0.058). In conclusion, the use of this new methodology for the evaluation of the mucoactive drug effect in OME has shed light into methodological pitfalls of clinical trials to date and underlines the need for agreed outcome measures, which may modify medical policy, which addresses more and more often to symptomatic treatment.

PCNA--a cell proliferation marker in vocal cord cancer. Part II: Recurrence in malignant laryngeal lesions.

Laryngeal squamous cell carcinoma constitutes the most frequent carcinoma found in the head and neck region. A precise prediction for recurrence potential cannot be done on site, treatment and histologic grading. Since Proliferating Cell Nuclear Antigen (PCNA) and DNA-cytometry have shown a good correlation between premalignant lesions and their progressive potential towards full-fledged carcinoma in the larynx as described in part I of this work, we have analyzed the PCNA index and DNA cytometry in specimen taken from vocal chord carcinomas with a 5-year follow-up, in order to assess its relationship with the presence or absence of tumour progression. 42 cases with (21) and without (2) recurrence have been examined. The DNA-index ranged from 1.01 to 1.43 (mean 1.10) in the group without and from 1.02 to 1.59 (mean 1.38) in the group with recurrent carcinoma (p = 0.002). The PCNA-index ranged from 0.00% to 18.90% (mean 6.97%) in the nonrecurrent group and from 0.00 to 3g.50% (mean 16.35%) in the patients with recurrence (p = 0.001). Both indices also correlated in a highly significant way. From these data emerges a highly significant correlation between the cytometric indices of cell proliferation and PCNA immunostaining. Furthermore the high correction between PCNA and DNA-index is of special interest for single case assessment. High DNA aberration and PCNA-index in vocal chord carcinoma may indicate a higher cellular aggressiveness of the tumour, resulting in a greater overall risk of metastases and local recurrences. Our results support the thesis that the indices of cellular proliferation within some cancers can define subsets of patients of high risk and help in isolating a population in which a more aggressive clinical protocol may be proposed.

PCNA--a cell proliferation marker in vocal chord cancer. Part I: Premalignant laryngeal lesions.

Laryngeal hyperkeratotic lesions can progress to fully developed malignant carcinoma in some cases. These premalignant lesions are proliferative disorders whose potential for further tumour progression is perhaps difficult to assess by mere histology. Immunostaining with PCNA, a protein correlated with cell proliferation, has been used to study tissue behavior in 30 cases of premalignant laryngeal vocal chord lesions treated by epithelial stripping in microlaryngoscopy, 15 of whom had no progression and 15 had recurrence and final development of full malignancy. The results showed a statistically significantly higher PCNA-index in the cases which underwent further tumour progression towards malignancy. PCNA testing may thus be suggested as a marker for tumour progression potential and help in determining clinical treatment choices.

[Exercise rhinomanometric test in the diagnosis of vasomotor rhinopathy]. / Il test da sforzo nella diagnosi di rinopatia vasomotoria.

The Authors examined 55 patients divided into two groups, one of 30 vasomotor rhinopatic patients and the other of 25 normal subjects. The aim of the study was to set up an objective diagnostic rhinomanometer test through observation and evaluation of reaction brought about by physical exertion following an exertion test of 5 minutes which employed a computerized climb simulator. Nasal resistance was measure before and immediately after exertion and then at intervals of 10, 20 and 50 minutes. Our data reveal a noteworthy decrease in nasal resistance brought about by the sympathetic nervous system in normal and rhinopathic subjects. Return to pre-exertion values, however occurred difference in the two groups: in the control group nasal resistance returned to pre-exertion values slowly, while in the rhinopathic group, it decreased rapidly and a rebound effect was observed. In vasomotor rhinopathy the orthosympathetic system is overcome by the para sympathetic system with regard to nasal vascularization control and, therefore, in rhinopatic patients exertion stimulates efficacions activation of the orthosympathetic system a phenomenon which does not occur in healthy subject. On the basis of our results an intensive stimulus such as physical exertion seems to have a different effect on the two groups suggesting that the vessels of nasal mucosa do not always respond in the same way, and that in vasomotor patients there is an alternate reactivity of neural control of nasal mucosa. The rhinomanometric exercise test seems to be useful in revealing this phenomenon and to be diagnostically reliable. The method is easily reproducible, non-invasive and can be usefully applied in clinical practice associated with the normal rhinomanometric challenge test.