Erythropoietin and erythropoietin receptor expression in head and neck cancer: relationship to tumor hypoxia.

PURPOSE: Erythropoietin, an oxygen-regulated glycoprotein hormone, is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor [erythropoietin receptor (EPOR)]. The recombinant form of human erythropoietin is used to prevent or treat anemia in cancer patients. However, in a recent randomized, placebo-controlled trial involving patients receiving curative radiotherapy for squamous cell carcinoma of the head and neck, erythropoietin treatment was associated with poorer locoregional progression-free survival. The purpose of our study was to determine whether EPOR and its ligand erythropoietin are expressed in primary head and neck cancer. We also investigated the hypothesis that erythropoietin expression in malignant cells may be associated with the presence of tumor hypoxia, an important factor involved in resistance to radiation treatment, tumor aggressiveness, and poor prognosis. EXPERIMENTAL DESIGN: Twenty-one patients received an i.v. infusion of the hypoxia marker pimonidazole hydrochloride before multiple tumor biopsies. Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for EPOR and erythropoietin expression and pimonidazole binding. RESULTS: EPOR expression was present in tumor cells in 97% of the biopsies. Coexpression of erythropoietin was observed in 90% of biopsies. Erythropoietin and pimonidazole adduct staining did not always colocalize within tumors, but there was a significant positive correlation between levels of microregional erythropoietin expression and pimonidazole binding. CONCLUSIONS: The coexpression of erythropoietin and EPOR in tumor cells suggests that erythropoietin may potentially function as an autocrine or paracrine factor in head and neck cancer. The expression of the hypoxia-inducible protein erythropoietin in tumor cells correlates with levels of tumor hypoxia.     

A Comparative Study: Evaluation of Antioxidant Activity of Melatonin and Some Indole Derivatives

To understand antioxidant activity and the role played by melatonin, we have designed and tested several new compounds. We present the results in terms of structure-activity relationships, focusing on the lack of the methoxy group and the influence of the amide side chain. Antioxidant activity of melatonin and some new melatonin analogue indole derivatives were investigated, using lipid peroxidation and superoxide anion radical scavenger activity assays, in rat liver tissue homogenate. Most of the compounds were found to be very potent inhibitors of malondialdehyde (MDA) formation at 10⁻³M. Inhibition rates ranged from 75-44 %. However, no significant inhibitory effect was obtained on superoxide anion formation. Consequently, it can be concluded that these compounds exhibit important LP activity compared to melatonin.     

Laryngopyocele: signs on computed tomography

A laryngocele is an air-filled dilation of the saccule of the larynx. An infected laryngocele is called a laryngopyocele. Our experience with a case of laryngopyocele with signs on computed tomography before and after antibiotic therapy is presented since laryngopyocele is more unusual.     

The electromyographic analysis of orbicularis oculi muscle in epiphora

Purpose:Functional epiphora is a clinical condition that presents with the complaint of watery eyes, but without anatomical stenosis in the lacrimal drainage system. Although the mechanism is not clear, there are various possibilities involving the movement of the orbicularis oculi muscle, especially its deeper segment (Horner’s muscle). We aimed to evaluate the function of the orbicularis oculi muscle in patients with patent, but dysfunctional lacrimal drainage system using a quantitative motor unit potential (MUP) analysis.Methods:Twenty-eight patients with functional epiphora (mean age = 59 years) and a control group of 28 volunteers were included in the study. Inclusion criteria were persistent and symptomatic epiphora or wiping >10 times per day and diagnosis confirmation by lacrimal irrigation test. Electromyography (EMG) was performed on the deeper segment of the orbicularis oculi muscle (medial and lateral parts). MUP parameters (duration time, amplitude, number of phases, number of turns, area, rise time, and thickness) were evaluated in both groups. Any increase in amplitude, prolongation time (>14 ms), number of turns, and satellite potential was taken as characteristic of the neurogenic type of epiphora, whereas shortened motor unit duration time, increased phase number, and low amplitude are the features of myopathic type.Results:Upon MUP analysis of the medial and lateral orbicularis oculi muscle, the increase in duration and thickness values in the medial part and the increase in duration, amplitude, area, and thickness values of the lateral part were found to be statistically significant in the patient group compared to the control group (P < 0.001). In the evaluation of the patients’ medial and lateral orbicularis oculi muscle, the increase in phase values and decrease in amplitude, area, and rise time values were found to be statistically significant (P = 0.024, P < 0.001, P < 0.001, and P = 0.010, respectively).Conclusion:These data show that functional epiphora is due to neurogenic damage of the orbicularis oculi muscle and should be investigated in more detail.     

Delayed Diagnosis of Tuberculous Arthritis

Monoarticular tuberculosis （TB） affecting the knee is rare in all forms of TB （0.1-0.3%）. We present the case of a patient with tuberculous arthritis in whom the diagnosis was belated due to a lack of familiarity with the disease; here, we emphasize the difficulties associated with the diagnosing joint TB. A 20-year-old man was referred to our department due to swelling of the right knee and the presence of persistent, mild pain for 4 years. The lack of systemic evidence of this disease, the indolent course of disease, and the presence of non- specific symptoms renders early recognition of this disease difficult. Furthermore, in cases in which a diagnosis cannot be reached simply by culturing the synovial fluid, synovial biopsy cultures should be considered m the diagnostic process, due to the high rate of positivity of such cultures. The diagnosis and treatment of articular TB are both urgent matters; surgical debridement and strict adherence to antituberculous chemotherapy tend to yield a satisfactory functional outcome.     

Predictors of malignancy in patients with solitary pulmonary nodules undergoing pulmonary resection

BackgroundThe management of a solitary pulmonary nodule is a challenging issue in pulmonary disease. Although many factors have been defined as predictors for malignancy in solitary pulmonary nodules, the accurate diagnosis can only be established with the permanent histological diagnosis.ObjectiveWe tried to clarify the possible predictors of malignancy in solitary pulmonary nodules in patients who had definitive histological diagnosis.MethodsWe made a retrospective study to collect the data of patients with solitary pulmonary nodules who had histological diagnosis either before or after surgery. We made a statistical analysis of both the clinic and radiological features of these nodules with respect to malignancy both in contingency tables and with logistic regression analysis.ResultsWe had a total of 223 patients with a radiological diagnosis of solitary pulmonary nodule. Age, smoking status and pack years of smoking, maximum standardized uptake value (SUVmax), and radiological features such as solid component, spiculation, pleural tag, lobulation, calcification, and higher density were significant predictors of malignancy in contingency tables. Age, smoking status and smoking (pack/year), SUVmax, and radiological features including spiculation, pleural tag, lobulation, calcification, and higher density were the significant predictors in univariate analysis. However, multivariate analysis revealed only SUVmax greater than 2.5 (p < 0.0001), spiculation (p = 0.009), and age older than 61 years (p = 0.015) as the significant predictors for malignancy.ConclusionAge, SUVmax, and spiculation are the independent predictors of malignancy in patients with solitary pulmonary nodules.     

Iridoid glycosides from Globularia trichosantha

A new iridoid glycoside, deacetylalpinoside (2), was isolated from the aerial parts of Globularia trichosantha together with nine known iridoid glycosides: catalpol, 10-O-benzoyl-catalpol, aucubin, asperuloside, deacetylasperuloside, asperulosidic acid, scandoside, geniposidic acid, and alpinoside (1). From the underground parts of the same plant, two new bisiridoid glycosides, globulosides A (3) and B (4); a known iridoid glycoside, globularidin; a lignan glycoside, liriodendrin; and seven phenylethanoid glycosides, arenarioside, verbascoside (= acteoside), isoacteoside, crenatoside, isocrenatoside, and trichosanthosides A and B, were isolated. Compounds 2-4 are new iridoids containing an 8,9 double bond representing a rare carbon skeleton. Their structures were established by spectroscopic methods.     

The composition, geographical variation and antimicrobial activity of Lippia javanica (Verbenaceae) leaf essential oils

Lippia javanica is widely distributed throughout South Africa where it is used extensively in traditional herbal preparations. An infusion of the leaves is commonly used as a decongestant for colds and coughs. A preliminary study indicated that the essential oil chemistry varies dramatically both within and between natural plant populations. As the antimicrobial activity may be directly related to the specific composition of the oil, the activity may also fluctuate. The aerial parts of Lippia javanica were collected from various localities in southern Africa to study the essential oil composition and the antimicrobial activity thereof. The hydrodistilled essential oils were analysed by GC/MS and a cluster analysis was performed on the essential oil dataset. From 16 samples (representing five natural populations), 5 chemotypes were identified; a myrcenone rich-type (36-62%), a carvone rich-type (61-73%), a piperitenone rich-type (32-48%), an ipsenone rich-type (42-61%) and a linalool rich-type (>65%). The myrcenone and linalool chemotypes have been mentioned in the literature but the carvone, ipsenone and piperitenone chemotypes have not previously been reported for Lippia javanica. Time kill studies were performed on three microbial respiratory isolates to document the scientific rationale of using Lippia to treat respiratory complaints in traditional herbal medicine. Klebsiella pneumoniae, Cryptococcus neoformans and Bacillus cereus showed reduction in microbial populations with the strongest bacteriostatic effect observed for Klebsiella pneumoniae.     

Anaphylactic reaction to polyethylene‐glycol conjugated‐asparaginase: Premedication and desensitization may not be sufficient

In hypersensitive reactions to native L‐asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG‐ASP) is preferred. Anaphylaxis with PEG‐ASP is rare. An 8‐year‐old girl and a 2.5‐year‐old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L‐asparaginase hypersensitivity and substitution with PEG‐ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG‐ASP infusion. Both patients developed anaphylaxis with peg‐asparaginase. These are the first reported cases of anaphylactic reaction to PEG‐ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG‐ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions.