Asthma phenotypes and lung function up to 16 years of age-the BAMSE cohort.

BACKGROUND: Asthma is a disease affecting many locations throughout the airway. Most studies have used spirometry as the primary assessment of airway obstruction, a method that may be less sensitive in regard to peripheral airway obstruction. The aim of this study was to elucidate the associations between asthma phenotypes based on age of onset and duration of symptoms, and (i) spirometry and (ii) small airway involvement measured by impulse oscillometry (IOS) in adolescence. METHODS: Children and adolescents taking part in BAMSE, a prospective birth cohort study, performed spirometry at 8 and 16 years and IOS at 16 years of age. Based on data collected in questionnaires, children were categorized into the following groups: 'never asthma', 'early transient asthma', 'early persistent asthma', and 'late onset asthma'. RESULTS: Compared with the never asthma group, all asthma groups were associated with lower FEV1 at 16 years of age (early transient-119 ml, 95% confidence interval -204 to -34; early persistent-410 ml, 95%CI -533; -287; and late onset-148 ml, 95%CI -237; -58). Between 8 and 16 years, significantly less increase in FEV1 was observed in the early persistent and late onset groups. The small airway index 'R5-20 ' was significantly associated with active asthma at 16 years, but not transient asthma. CONCLUSIONS: All asthma phenotypes studied were negatively associated with FEV1 in adolescence. IOS measurements indicated that active asthma could be associated with small airway impairments. These results provide new insights into the physiology underlying wheezing phenotypes based on age of onset and duration of disease.

Enterotoxin gene profiles of Staphylococcus aureus isolated from milk and dairy products in Italy.

UNLABELLED: Staphylococcal foodborne intoxication, occurring after consumption of staphylococcal enterotoxins (SEs) in food, is considered one of the most common forms of bacterial foodborne outbreaks worldwide. Milk and dairy products account for 5% of all the incriminated foods in staphylococcal outbreaks, referring to Europe. The distribution of genes encoding for enterotoxins in Staphylococcus aureus strains is highly variable, with some carried on stable regions of the chromosome and others carried on mobile genetic elements. The aim of this study was to analyse the distribution of genes encoding for SEs in Staph. aureus strains isolated from milk and dairy products. In the period from January 2010 to June 2011, a total of 1245 dairy samples (848 of raw milk and 397 of dairy products) were collected and analysed for detection of genes encoding for 11 SEs and SEls (SEA, SEB, SEC, SED, SEE, SEG, SEH, SEI, SER SElJ and SElP) according to the procedures of the Italian National Reference Laboratory for coagulase-positive Staphylococci including Staph. aureus. Staphylococcus aureus strains were isolated in 481 (39%) samples. Of the 481 isolates of Staph. aureus tested, 255 (53%) were positive for one or more SE genes, and thirty-five different enterotoxin gene profiles were distinguished among the isolates. ser gene, found in 134 (28%) of the isolates, was the most frequent, followed by sed (25%) and selj genes (25%). The identification of new SEs increased the isolation frequency of enterotoxigenic staphylococci, thus suggesting that the pathogenic potential of Staph. aureus may be of greater importance than previously thought. Further studies are needed to quantify the expression of these new enterotoxins, and to assess their contribution to foodborne disease burden. SIGNIFICANCE AND IMPACT OF THE STUDY: The analyses targeted 11 staphylococcal enterotoxins genes and 35 different enterotoxin gene profiles were distinguished among the isolates. A total of 255 Staph. aureus isolates were positive for one or more SE genes while ser gene was the most prevalent. In 93% of the isolates bearing genes located on the enterotoxin gene cluster (n = 89), both seg and sei genes were present.

Diffusion tensor magnetic resonance imaging of the normal breast: reproducibility of DTI-derived fractional anisotropy and apparent diffusion coefficient at 3.0 T.

PURPOSE: Diffusion-weighted imaging (DWI) may improve the diagnostic performance of conventional breast magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) is an extension of DWI. If DTI-derived measurements are to be clinically useful, particularly for predicting and/or monitoring therapeutic effects, they must be robust and reliable. The purpose of this study was to assess intra- and interobserver reproducibility of DTI-derived fractional anisotropy (FA) and apparent diffusion coefficient (ADC) at 3.0 T. MATERIALS AND METHODS: This prospective study was approved by the Institutional Review Board, and participants provided written informed consent. Sixty normal contralateral breasts of 60 patients (28-85 years, median 57) were analysed with a DWI sequence following a standard MRI protocol. Four authors performed all postprocessing and analyses independently and in different sessions. The same authors, blinded to the initial results, repeated the image postprocessing and analysis 4 weeks after the initial session. RESULTS: Mean ADC and FA for DTI sequences were, respectively, 1.92±0.30 and 0.32±0.09. Intra- and interobserver agreement of the four radiologists for ADC and FA were good (acceptable). Kappa values for ADC were intra-R1=0.82; intra-R2=0.84; intra-R3=0.89; intra-R4=0.88; inter-R1-R2=0.73; inter-R1-R3=0.74; inter-R1-R4=0.81; inter-R2-R3=0.76; inter-R2-R4=0.77; inter-R3-R4=0.83. Kappa values for FA were intra-R1=0.60; intra-R2=0.72; intra-R3=0.84; intra-R4 = 0.66; inter-R1-R2=0.64; inter-R1-R3=0.69; inter-R1-R4=0.72; inter-R2-R3=0.80; inter-R2-R4=0.71; inter-R3-R4=0.73. Within-subject coefficient of variation was 15% for ADC and 30% for FA. Repeatability with α=0.05 was 0.37×10-3 mm(2)/s for ADC and 0.112 for FA. CONCLUSIONS: ADC and FA measurements obtained with DTI are reproducible and may be valid, reliable and sensitive to change. ADC values obtained with DTI are more reproducible than FA.

Molecular differentiation of cattle Sarcocystis spp. by multiplex PCR targeting 18S and COI genes following identification of Sarcocystis hominis in human stool samples.

Sarcocystis spp. are protozoan parasites which can infect a wide range of vertebrates, including humans; the latter can act as definitive hosts for two cattle Sarcocystis spp.: Sarcocystis hominis and Sarcocystis heydorni. Reports of intestinal sarcocystosis are well documented in the literature, but PCR-based methods have been scarcely used to identify Sarcocystis species in human stools, and have been limited to the molecular analysis of 18S ribosomal RNA (18S rRNA) gene sequences. Since the mitochondrial cytochrome c oxidase subunit I (COI) gene is one of the most promising tools for distinguishing between closely related Sarcocystis spp., and taking into account the lack of publicly available S. hominis COI sequences, in the present study we obtained the first partial COI sequence of S. hominis from human stool samples of patient with gastrointestinal symptoms. We designed specific COI primers to develop a multiplex PCR method for the identification of Sarcocystis spp. in cattle. The submission of the COI sequence described herein and the unambiguous identification of S. hominis through the application of the new multiplex PCR is important for determining the prevalence of this zoonotic Sarcocystis spp. in meat and the risk for consumers.

Comparative analysis of confocal microscopy on fresh breast core needle biopsies and conventional histology.

BACKGROUND: Evaluation of core needle biopsies (CNB) is a standard procedure for the diagnosis of breast cancer. However, tissue processing and image preparation is a time- consuming procedure and instant on-site availability of high-quality images could substantially improve the efficacy of the diagnostic procedure. Conventional microscopic methods, such as frozen section analysis (FSA) for detection of malignant cells still have clear disadvantages. In the present study, we tested a confocal microscopy scanner on fresh tissue from CNB with intention to develop an alternative device to FSA in clinical practice. PATIENTS AND METHODS: In 24 patients with suspicious breast lesions standard of care image-guided biopsies were performed. Confocal images have been obtained using the Histolog™ Scanner and evaluated by two independent pathologists. Hematoxylin-Eosin (H&E) histological sections of the biopsies were routinely processed in a blinded fashion with respect to the confocal images. RESULTS: In total 42 confocal images were generated from 24 biopsy specimens, and available for analysis within a few minutes of taking the biopsy. This resulted in 2 × 42 = 84 pathologic evaluations. In four cases, a pathologic diagnosis was not possible with confocal microscopy. An exact correlation based on the B-classification was reached in 41 out of 80 examinations and in another 35 cases in a broader sense of correspondence definition (i.e. malignant vs. benign). CONCLUSIONS: As a reliable on-site method, the Histolog™ Scanner provides a visualization of cellular details equivalent to the H&E standards, permitting rapid and accurate diagnosis of malignant and benign breast lesions. Furthermore, this device offers great potential for immediate margin analysis of specimen in breast conserving therapy.

Correction to: Comparative analysis of confocal microscopy on fresh breast core needle biopsies and conventional histology.

Following publication of the original article [1], the authors reported an added data on Table 1 in their paper. The original article [1] has been updated.

Locoregionally advanced nasopharyngeal carcinoma: induction chemotherapy with cisplatin and 5-fluorouracil followed by radiotherapy and concurrent cisplatin: a phase II study.

BACKGROUND: Chemoradiotherapy is the current standard of care for locoregionally advanced nasopharyngeal carcinoma. The purpose of this study was to assess the feasibility and efficacy of induction chemotherapy (CHT) followed by concomitant chemoradiotherapy in this patient population. PATIENTS AND METHODS: In this single-arm, phase II study, patients with locoregionally advanced nasopharyngeal carcinoma were treated with 3 cycles of induction CHT with cisplatin (100 mg/m(2) on day 1) and 5-fluorouracil (1,000 mg/m(2) continuous infusion on days 1-4) followed by 3 cycles of cisplatin (100 mg/m(2) on days 1, 22 and 43) and concurrent radiotherapy up to 70 Gy. The primary endpoint was objective response. RESULTS: Thirty-four patients were enrolled, and all completed both induction treatment and subsequent chemoradiotherapy. Objective response rates were 79.4% (95% CI 62.1-91.3) and 85.3% (95% CI 68.9-95.0) after induction CHT and chemoradiation, respectively. Treatment was well tolerated and toxicity was manageable. At a median follow-up of 29 months, 3-year overall survival and progression-free survival rates are 80.0% (95% CI 0.64-0.95) and 54.0% (95% CI 0.36-0.73), respectively. CONCLUSIONS: Induction CHT with cisplatin and 5-fluorouracil followed by concomitant chemoradiotherapy is a feasible and active regimen for patients with stage IIB-IVB nasopharyngeal carcinoma. This regimen resulted in excellent locoregional disease control and overall survival.

Conservative and radical oncoplastic approches in the surgical treatment of breast cancer.

In the attempt to optimise the balance between the risk of local recurrence and the cosmetic outcomes in breast surgery, new surgical procedures, so-called oncoplastic techniques, have been introduced in recent years. The term oncoplastic surgery refers to surgery on the basis of oncological principles during which the techniques of plastic surgery are used, mostly for reconstructive and cosmetic reasons. The advantage of the oncoplastic surgery for breast cancer is the possibility of performing a wider excision of the tumour with a good cosmetic result. Oncoplastic surgery is a broad concept that can be used for several different combinations of oncological surgery and plastic surgery: excision of the tumour by reduction mammoplasty, tumour excision followed by remodelling mammoplasty, mastectomy with immediate reconstruction of the breast and partial mastectomy with reconstruction. Careful patient selection and preoperative planning are key components for the success of any oncoplastic operation for breast cancer. Accurate preoperative evaluation of the clinical and biological features of the tumour as well as of the morphological aspects of the breast allow the surgeon to make a decision if a conservative or radical approach is preferable and select the most effective oncoplastic surgical technique. In this review we summarise the indications, advantages and limitations of several oncoplastic procedures.

Cardiac function during breath-hold diving in humans: an echocardiographic study.

Breath-hold diving induces, in marine mammals, a reduction of cardiac output due to a decrease of both heart rate and stroke volume. Cardiovascular changes in humans during breath-hold diving are only partially known due to the technical difficulty of studying fully immersed subjects. Recently, a submersible echocardiograph has been developed, allowing a feasible assessment of cardiac anatomy and function of subjects during diving. Aim of the study was to evaluate, by Doppler-echocardiography, the cardiovascular changes inducedby breath-hold diving in humans. Ten male subjects were studied by Doppler echocardiography in dry conditions and during breath-hold diving at 3 m depth. In addition 14 male subjects were studied, using the same protocol, before and during breath-hold diving at 10 m depth. At 3 m depth significant reductions in heart rate (-17%), stroke volume (-17%), cardiac output (-29%), left atrial dimensions, and deceleration time of early diastolic transmitral flow (DTE) were observed. At 10 m depth similar but more pronounced changes occurred. In particular, increase in early transmitral flow velocity became significant (+33%), while DTE decreased by 34%. At both depths dimensions of right cardiac chambers remained unchanged. Breath-hold diving at shallow depth induced, in humans, cardiovascular changes qualitatively similar to those observed in natural divers such as seals. The reduced dimensions of left atrium associated to a left ventricular diastolic pattern resembling that of restrictive/constrictive heart disease, suggest that the hemodynamic effects of diving could be explained, at least in part, by a constriction exerted on the heart by the reduced chest volume and the increased blood content of the lungs. Finally, the absence of dimensional changes in the right chambers suggests that most of the pulmonary blood shift occurred before cardiac imaging.

Conservative treatment of the central breast cancer with nipple-areolar resection: an alternative oncoplastic technique.

Conservative surgery with radiation therapy is the standard treatment for early-stage breast cancer. Nevertheless, the patients with subareolar breast cancer have been often excluded from breast-conserving surgery and treated with mastectomy because of the unacceptable cosmetic effect associated with the resection of the nipple-areola complex (NAC), as well as oncologic concerns about multicentricity or multifocality associated with these tumours. We show a conservative "oncoplastic technique" in which the resection of the central portion of the breast, including the NAC, can allow a wide excision of the tumour with uninvolved margins of resection and good cosmetic results.

Update in the treatment of locally advanced breast cancer: a multidisciplinary approach.

Locally advanced breast cancer represents a wide variety of neoplasms and constitutes approximately 10%-20% of the newly diagnosed breast cancers. These cancers may have widely different clinical and biological characteristics. According to the American Joint Committee on Cancer (AJCC) staging system, all of stage III disease is considered locally advanced. The clinical treatment of locally advanced breast cancer is complex and should be tailored to the individual patient. In this paper we discuss the options of management of locally advanced breast cancer, focusing on a multidisciplinary approach through a combined-modality care involving surgery, radiotherapy and systemic therapy.

Management of locally advanced breast cancer. Mini-review.

The term locally advanced breast cancer (LABC) encompasses a heterogeneous group of breast neoplasms; in the last revision of the American Joint Committee on Cancer (AJCC) staging system, all of stage III disease is considered locally advanced. LABC constitutes up to 20% of breast cancer in medically underserved populations in the United States and up to 75% of breast cancers in developing countries. The prognosis depends on tumor size, extent of lymph node involvement, and the presence or absence of an inflammatory component. The clinical management of LABC is complex and should be tailored to the individual patient. However, a multidisciplinary approach is always recommended combining surgery, radiotherapy and systemic therapy (chemotherapy and/or hormone therapy). In this paper, we discuss the possible options in the management of operable (stage IIIA) and inoperable (stage IIIB-IIIC) LABC.

The evolution of surgery in the management of neck metastases.

In spite of advancement in science, molecular medicine and target therapies, surgical treatment of metastases using different techniques, from selective neck dissection to extended radical neck dissections, form a major part in the management of neck metastases. This is due to the fact that, so far, there is no treatment more effective for resectable neck metastases, than surgery. Since most head and neck cancer patients die due to loco-regional progression of disease, and a very large majority of them do not live long enough to develop distant metastases, the status of neck lymph nodes remains the single most important prognostic factor, in these cases. In the 100 years since George Washington Crile described Radical Neck Dissection, we now have a much better understanding of the biological and clinical behaviour of neck metastases. This has ultimately led to the conservative approaches of selective neck dissections depending on the primary site of the tumour, type of tumour and the characteristic features of the metastases themselves. A search of the literature on neck lymph nodes and neck dissections, on the internet and in old publications, not available in the electronic media, has been carried out. Using this as the basis, we arranged, in sequence, the dates of various landmarks in the treatment of head and neck cancer related to neck dissections to emphasize the overall process of evolution of neck dissection thereby showing how the field of head and neck surgery has travelled a long way from radical neck dissection to its modifications and further to selective neck dissections and sentinel node biopsies. The present understanding of the patterns of neck metastases enables us not only to adequately treat the neck metastases, but also to diagnose metastases from unknown primaries. Therefore, depending on the site of the primary tumour, it is now easy to predict the most probable route of metastatic spread and vice versa. This has enabled us to adopt modified and selective neck dissections which have ultimately led to a dramatic reduction in morbidity and almost eliminated mortality due to neck dissection. In the near future, molecular diagnostics and targeted therapies for treating metastases should be able to further reduce the burden of head and neck cancer.

The evolution of surgery in the management of neck metastases.

In spite of advancement in science, molecular medicine and target therapies, surgical treatment of metastases using different techniques, from selective neck dissection to extended radical neck dissections, form a major part in the management of neck metastases. This is due to the fact that, so far, there is no treatment more effective for resectable neck metastases, than surgery. Since most head and neck cancer patients die due to loco-regional progression of disease, and a very large majority of them do not live long enough to develop distant metastases, the status of neck lymph nodes remains the single most important prognostic factor, in these cases. In the 100 years since George Washington Crile described Radical Neck Dissection, we now have a much better understanding of the biological and clinical behaviour of neck metastases. This has ultimately led to the conservative approaches of selective neck dissections depending on the primary site of the tumour, type of tumour and the characteristic features of the metastases themselves. A search of the literature on neck lymph nodes and neck dissections, on the internet and in old publications, not available in the electronic media, has been carried out. Using this as the basis, we arranged, in sequence, the dates of various landmarks in the treatment of head and neck cancer related to neck dissections to emphasize the overall process of evolution of neck dissection thereby showing how the field of head and neck surgery has travelled a long way from radical neck dissection to its modifications and further to selective neck dissections and sentinel node biopsies. The present understanding of the patterns of neck metastases enables us not only to adequately treat the neck metastases, but also to diagnose metastases from unknown primaries. Therefore, depending on the site of the primary tumour, it is now easy to predict the most probable route of metastatic spread and vice versa. This has enabled us to adopt modified and selective neck dissections which have ultimately led to a dramatic reduction in morbidity and almost eliminated mortality due to neck dissection. In the near future, molecular diagnostics and targeted therapies for treating metastases should be able to further reduce the burden of head and neck cancer.

Discontinuous vs. in-continuity neck dissection in carcinoma of the oral cavity. Experience of two oncologic hospitals.

Many Authors have discussed the best indication and extension of neck dissection, but few have studied the surgical approach considering the continuity of neck dissection with the primary tumour. This retrospective study refers to patients submitted to major surgery between 1996 and 2001 for floor of mouth and oral tongue squamous cell carcinoma, at the Head and Neck Surgery Department of the Hospital "A.C. Camargo", São Paulo, Brazil and of the European Institute of Oncology, Milan, Italy. Patients were assigned to one of three groups: group I (in-continuity resection); group 2 (discontinuous resection) and group 3 (delayed discontinuous resection). Overall, 193 patients were studied. There were no differences in disease-free survival between the neck dissection groups. Furthermore, no statistical differences were found in disease specific survival between the groups. Discontinuous neck dissection seems not to change the disease-free survival or disease-specific survival when compared to in-continuity neck dissection, in this retrospective study. A prospective randomized trial is necessary to confirm these results.

Prospects of chemoprevention of human cancers with the synthetic retinoid fenretinide.

Fenretinide or N-(4-hydroxyphenyl)retinamide is a vitamin A analogue synthesized in the United States in the late 1960s. This retinoid shows a preferential accumulation in breast instead of liver, is effective in the inhibition of chemically induced mammary carcinoma in rats, and has proved to be less toxic than many other vitamin A analogues. The Milan Cancer Institute has put a particular effort in this molecule in both the experimental and clinical fields. We have demonstrated, in animals and humans, that fenretinide induces a rapid reduction of retinol plasma concentration, that its blood levels remain constant during administration for as long as 5 years, and that the drug is able to accumulate in the human breast. To date, 2969 stage I breast cancer patients have been randomized to evaluate the efficacy of this retinoid to prevent contralateral new primaries, 709 subjects have been accrued in a prevention trial of basal cell carcinoma of the head and neck, and 153 patients entered a study the preliminary results of which already show the capability of fenretinide to prevent recurrences and new localizations of oral leukoplakia. Further studies on fenretinide will be aimed at evaluating its preventive efficacy in superficial bladder and prostate cancers and at exploring possible synergism with tamoxifen and interferons in breast cancer and skin cancer, respectively.

Potential markers of tongue tumor progression selected by cDNA microarray.

Squamous cell carcinoma (SCC), the most frequent malignant tumor of the oral cavity, generally exhibits a poor prognosis and metastases are the main cause of death. This tumor often arises from pre-malignant lesions. To date, it is difficult to predict if and which pre-malignant lesions may progress into oral SCC using traditional methods. For these reasons, several studies are trying to identify markers useful in the progression of pre-malignant lesions and tumors. To define the genetic expression profile of tongue tumor progression we compared 9 dysplasias (DS), 8 tumors without metastasis (TWM), 11 metastasizing SCCs (MT) of the tongue, and a baseline of 11 normal tissues by using cDNA microarray containing 19.2 K clones. We initially applied hierarchical agglomerative clustering based on information from all 6026 clones. Results were obtained by performing a two steps analysis: a Significance Analysis of Microarray (SAM) and a Gene Ontology search. One hundred and five clones have statistically significant different expression levels (FDR < 0.01) between DS and TWM, whereas 570 genes have statistically significant difference expression levels between TWM and MT (FDR < 0.01) as detected by SAM. By filtering with FatiGo only 33 genes were differentially expressed in TWN, respect to DS, whereas 155 genes were differentially expressed in MT respect to TWM. We detected some genes which encode for oncogenes, transcription factors and cell cycle regulators as potential markers of DS progression. Examples are BAG4, PAX3 and CCNI, respectively. Among potential markers of metastases are some genes related to cell mobility (TSPAN-2 and SNTA1), intercellular adhesion (integrin alpha 7) or extracellular matrix components (ADAMTS2 and cathepsin O). Additionally, under-expressed genes encoded apoptosis-related proteins (PDCD4 and CASP4). In conclusion, we identified several genes differentially expressed in tumor progression which can potentially help in better classifying pre-malignant lesions and tongue SCCs.

Diagnosis and management of neck metastases from an unknown primary.

Neck lymph node metastases from occult primary constitute about 5%-10% of all patients with carcinoma of unknown primary site. Metastases in the upper and middle neck (levels I-II-III-V) are generally attributed to head and neck cancers, whereas the lower neck (level IV) involvement is often associated with primaries below the clavicles. Diagnostic procedures include a careful clinical evaluation and a fiberoptic endoscopic examination of the head and neck mucosa, biopsies from all suspicious sites or blindly from the sites of possible origin of the primary, computerized tomography scan, and magnetic resonance. The most frequent histological finding is Squamous Cell Carcinoma, particularly when the upper neck is involved. In these cases, a systematic tonsillectomy in the absence of suspicious lesions is discussed since up to 25% of primary tumours can be detected in this site. Thoracic, and abdominal primaries (especially from lung, oesophagus, stomach, ovary or pancreas) should be sought in the case of adenocarcinoma and involvement of the lower neck. Positron emission tomography with fluoro-2-deoxy-D-glucose allows detection of primary tumour in about 25% of cases, but this procedure is still considered investigational. Therapeutic approaches include surgery (neck dissection), with or without post-operative radiotherapy, radiotherapy alone and radiotherapy followed by surgery as reported by several guide-lines. In early stages (N1), neck dissection and radiotherapy seem to have similar efficacy, whereas more advanced cases (N2, N3) require combined approaches. The extent of radiotherapy (irradiation of bilateral neck and mucosa versus ipsilateral neck radiotherapy) remains debatable. A potential benefit from extensive radiotherapy should be weighed against its acute and late morbidity and difficulties in re-irradiation in the case of subsequent primary emergence. The role of other methods, such as chemotherapy and hyperthermia, remains to be determined.

Successful topical treatment of oral lichen planus and leukoplakias with fenretinide (4-HPR).

Eight patients with diffuse (non-operable) pre-cancerous lesions (oral lichen or leukoplakias) were treated with fenretinidec (4-HPR) applied topically twice daily. After one month of therapy two patients had complete remission and the other six had a greater than 75% response. 4-HPR was well tolerated, and no local or distant side effects were observed. Topical treatment may be combined with oral administration at lower doses to obtain therapeutic results with less toxicity than observed with oral administration alone. A study to further evaluate the efficacy of topical treatment is in progress at our institute.

Double-blind study of nimesulide in divers with inflammatory disorders of the ear, nose and throat.

200 divers of either sex, aged 18 to 54 years, entered a double-blind study to compare the efficacy and tolerability of nimesulide 200 mg/day with those of seaprose S 60 mg/day in the treatment of nonbacterial inflammatory disorders of the ear, nose, and throat. At the end of the 1-week treatment period, both drugs were judged to be effective, with improvements and, in most cases, complete remission of all symptoms observed. Nimesulide showed greater clinical efficacy, and both drugs were well tolerated.