Spirulina in clinical practice: evidence-based human applications.

Spirulina or Arthrospira is a blue-green alga that became famous after it was successfully used by NASA as a dietary supplement for astronauts on space missions. It has the ability to modulate immune functions and exhibits anti-inflammatory properties by inhibiting the release of histamine by mast cells. Multiple studies investigating the efficacy and the potential clinical applications of Spirulina in treating several diseases have been performed and a few randomized controlled trials and systematic reviews suggest that this alga may improve several symptoms and may even have an anticancer, antiviral and antiallergic effects. Current and potential clinical applications, issues of safety, indications, side-effects and levels of evidence are addressed in this review. Areas of ongoing and future research are also discussed.

Reflux and sleeping disorders: a systematic review.

INTRODUCTION: Laryngopharyngeal reflux is perhaps the most extensively researched laryngology topic of the last decade. It has been suggested that some supraoesophageal symptoms, most notably asthma and laryngospasm, may be associated with night-time, or supine, reflux. The aim of this review was to assess the levels of evidence regarding a correlation between night-time reflux, snoring and apnoea. METHODS: A Medline search was performed using the terms 'reflux', 'night-time', 'larynx', 'gastroesophageal', 'laryngopharyngeal', 'sleep', 'apnoea', 'snoring' and 'ear nose throat'. The retrieved literature was reviewed, focusing on randomised and non-randomised, controlled, prospective trials. Papers on both paediatric and adult populations were included. Non-English language papers were excluded. RESULTS: We found no randomised, controlled trials or meta-analyses addressing the possible correlation between reflux and snoring and/or apnoea. CONCLUSIONS: The role of night-time reflux in paediatric and adult snoring and apnoea is well described in the literature, but is based on poor levels of evidence from uncontrolled studies and case reports.

Grisel's syndrome in otolaryngology: a systematic review.

AIMS: to assess etiology, treatment and outcome of Grisel's syndrome. METHODS: A Medline search was performed using the terms Grisel's syndrome, spontaneous atlantoaxial subluxation, head, neck, ear, nose and throat. A systematic review of the literature was performed. Case series of both adult and pediatric cases were included. Only papers focusing on true non-traumatic atlantoaxial subluxation were included. RESULTS: Seventy-one papers have been published from 1950 to 2006. Forty-eight of these fulfilled our inclusion criteria, totaling 103 patients for review. The main causes of Grisel's syndrome were infection (48%) and post-adenotonsillectomy (31%). Less common causes included other postoperative cases such as pharyngoplasty and ear operations. Neurosurgical consultation was paramount in all cases. In the majority of cases conservative management in the form of bedrest, antibiotics, muscle relaxants, traction and collar was effective; in a few cases only surgery in the form of arthrodesis was deemed necessary. Morbidity was significant in those cases where diagnosis was delayed, with the most devastating consequence a permanent neurological deficit in one case. CONCLUSIONS: Grisel's syndrome is a rare but dangerous complication that can go unnoticed in its early phase and can be a major cause of morbidity and mortality following infection or head and neck procedures/interventions. Early recognition of any cervical complication following routine otolaryngological operations together with early neurosurgical consultation is mandatory to prevent devastating consequences.

Expression of matrix metalloproteinase-9 (gelatinase B) in benign, premalignant and malignant laryngeal lesions.

The matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes, which are responsible for the breakdown of the extracellular matrix components in pathological and physiological conditions. They are involved in basement membrane disruption, stroma and blood vessel penetration, metastasis and more recently there is evidence that they participate in tumor growth and angiogenic events. Matrix metalloproteinase 2 and 9 (MMP 2 and 9) belong to the gelatinases, a subgroup of MMPs, and have the capacity to degrade the triple helix type IV collagen of basal lamina of the basement membrane. With the present study, we tried to demonstrate the expression of MMP-9 immunohistochemically, comparatively in benign, premalignant and malignant lesions of the larynx. We studied 154 laryngeal lesions including 55 squamous cell carcinomas, 8 in situ carcinomas, 54 cases of dysplasia (of low and intermediate grade), 13 papillomas and 24 cases of keratosis. Overexpression of MMP 9 was observed in 74.4% and 50% in invasive and in situ squamous cell carcinomas respectively. In dysplastic cases, in papillomas and in keratoses the percentage of overexpression was 62.9%, 61.53% and 54.16% respectively and the expression of MMP-9 was significantly higher in invasive squamous cell carcinomas compared to dysplasias (p=0.000004). Also significantly higher was the expression of MMP-9 in dysplastic cases compared to papillomas (p=0.023). The MMP-9 expression was related neither to survival nor to the other available clinicopathological parameters (tumor size, grade, clinical stage, lymph node status and patient age). In conclusion, our study indicates that the expression of MMP-9 is up-regulated in a stepwise fashion, with two main steps, the first one, when a dysplastic lesion evolves and the next one, when the dysplasia progresses to invasive carcinoma.

Cell cycle proteins in laryngeal cancer: role in proliferation and prognosis.

A study of laryngeal carcinomas was performed in order to analyze (a) the expression of p53/p21, cyclin D1/cyclin E, p21/p27 (b) the relation of normal and abnormal protein expression, with the proliferation status, as determined by the expression of Ki67 and PCNA and (c) the correlation of our findings with prognosis. We performed a retrospective analysis of 57 cases of squamous cell carcinomas of the larynx. We applied monoclonal antibodies against p53, p21, p27, cyclin D1, cyclin E, Ki67 and PCNA, using streptavidin-biotin method. Analysis of the p53/p21 proteins, revealed abnormalities in 25/37 cases (67.57%), while 12/37 (32.43%) cases displayed normal phenotype (p53-/p21-). Analysis of cyclins revealed overexpression in 17/48 cases (35.42), while the majority 31/48(64.58%) displayed normal phenotype (cyclin D1-/cyclin E-). Concerning CDKIs expression, the majority 30/50(60%) presented high levels of both inhibitors (p21+/p27+). Cases with simultaneous overexpression of CDKIs demonstrated significantly higher levels of Ki67 protein (p = 0.05). Analysis of p53/p21, cyclin D/cyclin E, p21/p27 patterns showed no association between the presence of one or two alterations and prognosis. In conclusion, we demonstrated that p53 tumor suppressor pathway is frequently disrupted in laryngeal cancer. Furthermore, levels of CDKIs, although they act as cell cycle activity blockers, are not reliable markers for the estimation of laryngeal neoplastic cells growth fraction.

Laryngeal involvement in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, which causes joint damage and bone destruction. Extra-articular manifestations are numerous, involving multiple organ systems. Rheumatoid nodules are common extra-articular findings occurring in 20% RA patients. They develop most commonly in pressure areas (elbows and finger joints) and may occasionally affect internal organs including pleura, lungs, meninges, larynx, and others. Furthermore, RA affects the ear, nose, and throat, causing various otorhinolaryngological symptoms. In this report we describe two patients with RA and laryngeal involvement, mostly rheumatoid nodule formation, with a review of the literature.

Effects of cigarette smoking on the antioxidant defence in young healthy male volunteers.

Cigarette smoking induces a significant oxidant effect related to variety of free radical-related diseases often affecting the upper respiratory tract, unless it is effectively compensated by the antioxidant barriers of the humans. In the present study, the evaluation of the antioxidant compensatory mechanisms, by estimating the antioxidant capacity of extracellular defence (saliva and plasma) and the intracellular resistance of peripheral lymphocytes to oxidative stress in young healthy smokers, was investigated. Twenty young healthy male smokers and 20 age-matched non-smokers with similar dietary profiles were enrolled in the study. Total saliva and plasma samples were collected from both groups, and total antioxidant capacity (TAC) and lag time were estimated. The latter was also repeated in smokers just after a cigarette smoking. Peripheral lymphocytes isolated from the subjects of both groups were also tested for their inherent DNA damage as well as for their ability to resist H2O2-induced DNA damage by using the comet assay. TAC of plasma was found significantly higher in smokers compared to non-smokers (p <0.004), whereas no difference was recorded in plasma lag time values. Lymphocytes of smokers manifested a significantly decreased oxidant resistance (increased DNA fragmentation) to H2O2, in comparison to non-smokers. Our results indicate that young smokers do not manifest different salivary antioxidant defence than non-smokers. They exhibit, however, a higher plasma antioxidant capacity, but a significantly reduced ability of blood lymphocytes, to resist to H2O2-induced DNA damage.

A clinical case report of a Schwannoma on the tip of the tongue.

OBJECTIVES: Schwannomas (neurilemmomas) are benign solitary tumours which arise from the Schwann cells of the neural sheath, most often from the VIII cranial nerve. Extracranially, 25% of all schwannomas are located in the head and neck. Intra-oral development is uncommon and a location in the tongue has been reported in individual cases. METHODOLOGY: We present a young patient with a schwannoma in the distal right side of the tongue. RESULTS: The tumour had grown slowly producing no symptoms. The diagnosis was made on histological examination. Surgical enucleation of the mass was uncomplicated and there was no recurrence. CONCLUSIONS: We report a further case of a schwannoma of the tongue, highlighting the need for this to be considered in the differential diagnosis.

Pediatric middle ear infections and gastroesophageal reflux.

OBJECTIVES: The pathogenesis of middle ear infections in children is multifactorial and includes infection, anatomical factors, impaired immunologic status, allergy, familial predisposition, male sex, method of feeding and environmental factors. Glue ear remains the commonest cause of deafness in childhood. Gastroesophageal reflux (GOR) is a common problem in the newborn and preschool periods. Recent research suggests that it may be related to eustachian tube dysfunction and otitis media. METHODS: We review the literature and discuss the possible relationship between Gastroesophageal reflux and otitis media in children. CONCLUSIONS: The current data are not enough to support antireflux treatment in children with refractory middle ear infections. More prospective randomised placebo-controlled studies are needed.

Expression patterns of cyclins D1, E in laryngeal epithelial lesions: correlation with other cell cycle regulators (p53, pRb, Ki-67 and PCNA) and clinicopathological features.

The expression of cell-cycle progression molecules cyclin D1 and cyclin E were immunohistochemically examined in a series of 64 squamous cell invasive carcinomas of the larynx, 10 in situ carcinomas, 34 cases of dysplasia, 11 papillomas and 23 cases of keratosis. The results of their expression were compared with two cell-cycle implicated tumor suppressor proteins p53 and pRb as well as with two proliferation associated indices PCNA and Ki-67 in an attempt to elucidate their potential role in the pathogenesis and progression of these lesions. Nuclear staining for cyclin D1 and E (>5% positive cells) was observed in 19% and 39.7% of the laryngeal carcinomas, respectively. Significantly elevated levels of cyclin D1 and E in invasive laryngeal carcinomas compared with in situ carcinomas were revealed (p=0.045 and p=0.0003, respectively). High levels of cyclin D1 and E expression were correlated with increased Ki-67 score (p=0.037 and 0.017 respectively). A significant positive correlation between cyclin D1 and E was also detected in carcinomas (p=0.018). Decreased levels of cyclins D1 and E in the group of in situ carcinomas compared with those of dysplastic cases and papillomas were also observed. In the dysplastic lesions cyclin D1 expression was correlated with pRb expression (p=0.02). In the cases of keratosis cyclins D1 and E expression were correlated with pRb (p=0.002 and p=0.036, respectively), while cyclin D1 was associated with PCNA (p=0.008) and Ki-67 score (p=0.009). The prognostic significance of cyclins D1, E in determining the risk of recurrence and overall survival with both univariate (long-rang test) and multivariate (Cox regression) methods of analysis showed no statistically significant differences. We conclude that the expression of cyclins D1 and E in squamous cell carcinomas of the larynx does not seem to have a prognostic significance. In addition, their expression may be involved in the development of laryngeal lesions, implicated in cell proliferation, with other cell cycle related proteins, probably by different molecular pathways.

The role of CD44 in the development and prognosis of head and neck squamous cell carcinomas.

CD44, the product of a single gene, exists as several isoforms generated by alternative exon splicing and posttranslational modifications, and is widely distributed in different cells and tissues including those of squamocellular origin. CD44 is a cell surface glycoprotein involved in many cellular processes acting as a receptor for cell to cell or cell to matrix adhesion, as a signal transmitter and as a growth factor-presenting molecule. Numerous studies based on immunohistochemical analyses of paraffin-embedded or frozen tissue sections using different monoclonal antibodies to CD44 isoforms and molecular biological techniques have provided evidence that in many types of tumours there is overexpression of CD44 isoforms and aberrant processing of immature CD44 transcripts relative to non-neoplastic control tissues, suggesting a role of CD44 in tumour development and progression. In contrast to these malignancies, one or more of the CD44 splice-variant isoforms are down-regulated in squamous cell carcinomas of the head and neck. CD44-deficient mice develop normally without giving rise to spontaneous tumours, but CD44-negative cells appear to be more susceptible to oncogenic transformation. Reduction in the expression of CD44 may confer growth advantage and malignant properties to tumour cells. The clinical significance of CD44 in squamous cell carcinomas of the head and neck as a tumour marker for cancer diagnosis and prognosis is discussed.

Ramsay Hunt syndrome presenting as a cranial polyneuropathy.

Ramsay Hunt syndrome (RHS) is herpes zoster of the facial nerve, frequently associated with VIII cranial nerve involvement, but on rare occasions other cranial nerves are affected as well. We present the case of a 63-year-old woman with RHS with involvement of V, VII, VIII, IX, and XII cranial nerves. The patient showed significant improvement after treatment with acyclovir and prednisolone. RHS should be recognized as a polycranial neuritis characterized by damage to sensory and motor nerves, including the facial nerve and the auditory-vestibular apparatus. Early institution of treatment with antiviral agents may help hasten healing. Involvement of the XIIth cranial nerve has not been reported previously.

Seromucous maxillary sinusitis (SMMS): a clinicophysiological approach.

Chronic sinusitis, especially maxillary sinusitis is a common disorder in humans. Seromucous sinusitis is rarely described in the literature. The present study deals with the clinical and laboratory characteristics of a group of patients suffering from the above disorder. During the last 10 years, 32 patients suffering from seromucous maxillary sinusitis were enrolled in the study. Patients' charts were reviewed and tabulated according to age, sex, history, clinical symptoms and laboratory findings. Treatment was based on punction and drainage of the seromucous effluent. Results were also statistically evaluated. Flight trips and atypical episodes of nasal infection were the predisposing factors for seromucous maxillary sinusitis. The only clinical manifestation was coughing, for at least 12 weeks before diagnosis. Sinus effluent was composed by serous and mucous constituents with glue like structure. There were no differences between sexes in predisposing factors, or x-ray findings. The treatment is paracentesis and drainage and in one case of recurrence, middle meatotomy and sinus endoscopy.

Contribution of exfoliative cytology to the diagnosis of laryngeal lesions.

OBJECTIVE: To estimate the diagnostic accuracy and reliability of exfoliative laryngeal cytology. STUDY DESIGN: Over three years (1996-1999) cytologic smears were obtained from clinically suspicious laryngeal lesions during laryngoscopy in a total of 31 selected patients (28 males and 3 females with an age range from 28-90 years). The cytologic diagnoses were analyzed and correlated with the histologic and final clinical diagnoses in 17 and 14 cases, respectively. Cytologic identification of the exact histologic type of the lesion was evaluated in 17 patients from whom both cytologic smears and biopsy material were obtained. RESULTS: The overall specificity was 100%, with no false positive diagnoses. The overall sensitivity was 93.3%, with one false negative cytologic diagnosis, in a case of non-Hodgkin's lymphoma. Cytohistologic correlation showed complete agreement between cytologic and histologic diagnoses in five of six benign lesions, in four cases of dysplasia and in six cases of squamous cell carcinoma. The overall diagnostic accuracy of cytology was 96.7% CONCLUSION: Exfoliative cytology by the smear technique is a reliable and accurate method in clinically suspected laryngeal lesions. Moreover, exfoliative cytology may be applied as the only alternative diagnostic method, especially in elderly patients with coexistent cardiorespiratory problems, when biopsy is not advisable or indicated.

Prognostic significance of p53 in the cancer of the larynx.

p53 is a nuclear phosphoprotein acting as a transcription factor to regulate cell cycle progression and apoptosis, mediated by a number of target genes. p53 mutant proteins have lost a) the ability to act as sequence-specific transcription factors and b) their tumour suppressive properties. As p53 is the most commonly mutated gene in human cancer, including laryngeal squamous cell carcinoma, an aggressive and most frequent tumour of head and neck, it has attracted a great deal of interest as a prognostic factor, diagnostic tool and therapeutic target. This article reviews the current understanding of the prognostic significance of p53 in laryngeal squamous cell carcinoma. Immunohistochemical staining techniques and molecular genetics demonstrated that p53 activation is an early event in laryngeal squamous cell carcinogenesis but can not be used as a reliable prognostic marker.

Treatment of nasal polyposis in Byzantine times.

The goal of this study was to describe the therapeutic methods and surgical techniques used during Byzantine times (AD 324-1453) for a disease that has occupied physicians since antiquity: nasal polyps. The original Greek-language texts of the Byzantine medical writers, most of which were published after the 17th century, were studied in order to identify the early knowledge of the definition, symptoms, conservative treatments, and surgical intervention in cases of this disease. A considerable number of conservative treatments, etiologic and local (with inunctions or blowing of caustic substances), with evident influence from Roman medicine, were identified even in the early Byzantine medical texts (4th century). Further, some surgical techniques were described that seem to constitute evolution of the Hippocratic tradition. From the study of the original texts of Byzantine medical writers, their interest in the rhinological diseases is evident; in the case of nasal polyps, new techniques were mentioned. The first meticulous intranasal surgical removal of polyps was described. These techniques, obviously developed during the Hellenistic period, initially influenced European medicine and later the rest of the world.

Expression of the extracellular matrix protein tenascin in laryngeal epithelial lesions: correlation with fibronectin, CD44, cathepsin D and proliferation indices.

Tenascin (TN) is an extracellular matrix glycoprotein expressed in areas of epithelial-mesenchymal interactions during embryogenesis and in neoplasia. We studied the expression of TN in a series of 35 squamous cell invasive carcinomas of the larynx, 13 in situ carcinomas, 41 cases of dysplasia, 10 papillomas and 18 cases of keratosis using the monoclonal antibody TN2 on paraffin-embedded tissue. TN expression was correlated with the expression of fibronectin, CD44 and cathepsin D (CD) proteins, with the proliferation indices Ki-67 and proliferating cell nuclear antigen (PCNA) as well as with conventional clinicopathological variables. Malignant tumours showed a significantly greater stromal TN staining than benign lesions. In invasive carcinomas, the immunoreactivity was statistically higher than that in situ (P=0.01), dysplastic lesions (P<0.0001), papillomas (P=0.004) and keratosis (P<0.0001). A statistically significant difference of TN expression between in situ and dysplastic lesions was observed (P=0.001). In invasive lesions, TN expression was statistically correlated with CD44 expression (P=0.02) and a trend for correlation with CD of tumour cells and fibronectin expression was found (P=0.06 and P=0.09, respectively). The relationship of TN expression with the histological grade and the proliferative activity was insignificant. In conclusion, stromal TN expression may be involved in the complex mechanism of development of laryngeal lesions and may help to predict the risk of progression of pre-cancerous lesions to cancer.

Surgery on the larynx and pharynx in Byzantium (AD 324-1453): early scientific descriptions of these operations.

We present the techniques of various operations on the larynx and pharynx (incision of abscesses of the tonsils, tonsillectomy, tracheotomy, uvulectomy, and removal of foreign bodies) found in the Greek texts of Byzantine physicians. The techniques of these operations were the first to be so meticulously described and were compiled from the texts, now lost, of the ancient Greek physicians. These medical texts, which followed and enriched the Hippocratic, Hellenistic, Roman, and Galenic medical traditions, later influenced medieval European surgery, either directly through Latin translations or indirectly through works of Arab physicians.