Complete concentric collapse at the soft palate in sleep endoscopy: what change is possible after UPPP in patients with CPAP failure?

Purpose

The aim of this work was to assess whether uvulopalatopharyngoplasty in patients with failure for positive airway pressure not only reduces the degree of obstructive sleep apnea but also to determine as well if it changes the collapse pattern of the soft palate and thereby fulfills the qualifications for implementing upper airway stimulation (UAS) as an adjunctive solution.

Method

Fifteen patients with intolerance for positive airway pressure were included in this retrospective cohort study. Polygraphy and drug-induced sleep endoscopy were used in order to evaluate the reduction of the apnea-hypopnea index (AHI), as well as the change of collapse pattern at the soft palate level before and about 3 months after uvulopalatopharyngoplasty and tonsillectomy (TE-UPPP).

Results

In 93% of the patients, a postoperative change of the initially complete concentric palatal collapse pattern could be found during drug-induced sleep endoscopy. In one patient, no obstruction at all was seen at the soft palatal level. Only one patient still presented with a complete concentric collapse at velum level. AHI decreased from mean 34.7 events per hour to 20.2/h and oxygen desaturation index from 25.3 events per hour to 16.1/h.

Conclusion

Patients seeking for positive airway pressure alternatives could not only benefit from reduction of AHI by TE-UPPP postoperatively; additionally, by changing the collapse pattern at the soft palate, they might also fulfill criteria for upper airway stimulation (UAS) in case of persistent OSA of at least moderate degree.

     

Stem cells in squamous head and neck cancer

The initiation and metastasis of head and neck squamous cell carcinomas (HNSCC) and other cancers have recently been related to the presence of cancer stem cells (CSC). CSC are cancer initiating, sustaining and are mostly quiescent. Specific markers that vary considerably depending on tumor type or tissue of origin characterize putative CSC. Compared to the bulk tumor mass, CSC are less sensitive to chemo- and radiotherapy and may also have low immunogenicity. Therapeutic targeting of CSC may improve clinical outcome of HNSCC which has two distinct etiologies: infection of epithelial stem cells by high-risk types of the human papillomavirus, or long-term tobacco and alcohol abuse. Recent knowledge on the role of CSC in HNSCC is reviewed and where necessary parallels to CSC of other origin are drawn to give a more comprehensive picture.     

Expression and function of the mannose receptor CD206 on epidermal dendritic cells in inflammatory skin diseases

The capability to take up mannosylated protein antigens is important for the biologic function of dendritic cells, as many glycoproteins derived from bacteria and fungi, e.g., Malassezia furfur, are mannosylated. The expression of the mannose receptor CD206 has been regarded a differentiation hallmark of immature dendritic cells, whereas monocytes and mature dendritic cells as well as epidermal Langerhans cells do not express CD206. This study describes some epidermal dendritic cells that may express CD206 under inflammatory skin conditions: Immunohistochemical and flow cytometric analysis with the CD206-specific D547 antibody confirmed that Langerhans cells from normal human skin do not express CD206. Epidermal cell suspensions from atopic dermatitis and psoriasis revealed two distinct subsets of epidermal dendritic cells: a CD1a(+++)/CD206(-) cell population (i.e., Langerhans cells) and a CD1a(+)/CD206(++) cell population, corresponding to the previously described inflammatory dendritic epidermal cells. CD206-mediated endocytosis, assessed by dextran-fluorescein isothiocyanate uptake, was demonstrated in inflammatory dendritic epidermal cells but not in Langerhans cells. CD206-independent uptake of the fluorescent dye Lucifer yellow, a pinocytosis marker, was demonstrated in both Langerhans cells and inflammatory dendritic epidermal cells. Electron microscopic examination, known to distinguish Langerhans cells from inflammatory dendritic epidermal cells by their Birbeck granules, revealed Langerhans cells with Birbeck granules and inflammatory dendritic epidermal cells without Birbeck granules. Inflammatory dendritic epidermal cells exhibited numerous coated pits and vesicles, the latter fusing with large endosome-like structures, thus suggesting a high endocytotic activity. Immunogold staining with D547 monoclonal antibody confirmed that inflammatory dendritic epidermal cells were positive for CD206. In conclusion, inflammatory dendritic epidermal cells but not Langerhans cells are expressing CD206 in situ and use it for receptor-mediated endocytosis.     

mTOR inhibitors show promising in vitro activity in bladder cancer and head and neck squamous cell carcinoma

Bladder cancer and head and neck squamous cell carcinoma (HNSCC) are frequent but lack efficient therapies especially in advanced disease. Almost no studies on mTOR function and inhibition in these tumor entities have been reported. We examined the gene and protein expression levels of mTOR and its activated form (pmTOR) in three human bladder carcinoma cell lines (RT-4, T24, EJ28) and three HNSCC cell lines (PCI-1, PCI-13, BHY). Furthermore, the consequences of mTOR inhibition by mTOR-specific siRNAs and the mTOR inhibitor temsirolimus were analysed in vitro using immunohistochemical Ki-67 staining, mTOR and pmTOR western blot analysis, MTT assay, as well as cell cycle analysis with flow cytometry. Especially pmTOR protein expression levels showed marked differences between cell lines. siRNA transfection was associated with dose-dependent target protein reduction but not proliferation inhibition or apoptosis. On the contrary, temsirolimus significantly reduced cell viability and induced apoptosis and cell cycle arrest. According to these data, bladder cancer and HNSCC are promising tumor entities for mTOR inhibition with temsirolimus.     

Drug-induced Sweet's syndrome after mitoxantrone therapy in a patient with multiple sclerosis

We report a 55-year-old male patient with secondary progressive multiple sclerosis who developed an acute febrile syndrome with fever, neutrophilia and tender erythematous plaques and papules on his upper extremities after his fifth mitoxantrone infusion. Infectious, haematological and rheumatological diseases were ruled out, but skin biopsy showed neutrophilic infiltrations in the dermis consistent with Sweet's syndrome. Treatment with oral corticosteroids led to prompt improvement of systemic and cutaneous symptoms. To our knowledge, this is the first report of a patient with Sweet's syndrome after mitoxantrone therapy. Clinicians should be aware of Sweet's syndrome in patients with otherwise unexplained acute febrile illness and erythematous skin rash in association with mitoxantrone therapy. Skin biopsy helped to exclude other diseases and confirmed Sweet's syndrome.     

The Munich outbreak of cutaneous cowpox infection: transmission by infected pet rats

Cowpox virus infection of humans is an uncommon, potentially fatal, skin disease. It is largely confined to Europe, but is not found in Eire, or in the USA, Australasia, or the Middle or Far East. Patients having contact with infected cows, cats, or small rodents sporadically contract the disease from these animals. We report here clinical aspects of 8 patients from the Munich area who had purchased infected pet rats from a local supplier. Pet rats are a novel potential source of local outbreaks. The morphologically distinctive skin lesions are mostly restricted to the patients' necks, reflecting the infected animals' contact pattern. Individual lesions vaguely resemble orf or Milker's nodule, but show marked surrounding erythema, firm induration and local adenopathy. Older lesions develop eschar, leaving slow-healing, deep ulcerative defects after eschar separation. Severe flu-like illness may be present in the acute phase. Smallpox-vaccinated patients tend to develop less severe reactions and heal more quickly. The differential diagnosis may include other localized orthopoxvirus infections, herpes simplex, bacterial infection, anthrax, foreign body granuloma, and primary tuberculosis. Dermatologists should be aware of the diagnostic and therapeutic algorithms for handling this disease.     

Neue Tyrosinkinase- und EGFR-Inhibitoren in der Tumortherapie

Recently, inhibitors of the epidermal growth factor receptor (EGFR) and multikinase inhibitors have been successfully established in the therapy of various solid tumors. EGFR inhibitors and multikinase inhibitors are specific and selective agents that intervene with the dysfunctional regulatory processes of malignant cells. This results in a favorable safety profile and range of side effects, especially in comparison to conventional chemotherapy. The various cutaneous adverse drug reactions are considered substance class effects and are the most frequent side effects of these targeted therapies. Therapy with EGFR inhibitors is associated with acneiform rash, painful paronychia, xerosis cutis, acral fissures, hair changes, and pruritus. Treatment with tyrosin kinase inhibitors may cause hand-foot syndrome, various types of drug rash, hair loss, xerosis cutis, and pruritus. These side effects may be stigmatizing and place a huge burden on the patient's quality of life. Treatment is a challenge and best performed in interdisciplinary cooperation of dermatologists and oncologists.     

Multicentre evaluation of performance of C-reactive protein analysis over a one-year period

This communication deals with a longitudinal evaluation of C-reactive protein (CRP) analysis during a one-year period using a single lot of liquid control sera (3 levels) (BIOREF-CRP levels 1, 2 and 3) in different laboratories. A total of 652 sets of data were returned from 20 participating laboratories using 13 different reagent-measuring device combinations. The use of the control materials was defined in a standard operating procedure. Data was returned to the organizers on a monthly basis and questions could be asked or problems presented during the evaluation period. Although the performance of different reagents varied, the control materials were shown to be stable over the whole of the evaluation period when stored at 4-7 degrees C in a refrigerator/cold room. Typical problems were encountered, examples of which are presented here in graphical and tabular form.