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.     

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.     

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.     

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.     

Functional pulmonary atresia in a patient with neonatal Marfan syndrome caused by a c.3602G>A mutation in exon 29 of the FBN1 gene

Neonatal Marfan syndrome is a severe form of the syndrome mostly caused by de-novo mutations in the fibrillin-1 gene. We report a newborn with neonatal Marfan syndrome and functional pulmonary atresia who died from congestive heart failure on postnatal day 22 despite treatment. He had a mutation in exon 29 of the fibrillin-1 gene at position c.3602G>A. Functional pulmonary atresia may be a life-threatening cardiovascular manifestation of neonatal Marfan syndrome.     

Ultrasound screening for fetal major abnormalities at 11-14 weeks

BACKGROUND: This study was planned to evaluate the efficiency of the 11-14 week scan in detecting fetuses with major fetal structural abnormalities. METHODS: Some 1,290 pregnant women were submitted to a routine ultrasound scan between the 11th and 14th week after the detection of the fetal viability. The fetal anatomy was examined transabdominally, and in suspected cases transvaginally. Following the scans, the patients were examined in the second or third trimester of pregnancy. Fetal structural abnormalities classified as major and early onset were noted. Isolated choroid plexus cysts, cardiac defects not requiring treatment, mild ventriculomegaly, and mild renal pelviectasis in second trimester were not included. RESULTS: Twenty-four (1.86%) fetuses with various defects were identified, and 17 of these were diagnosed at the 11-14 week scan. The antenatal ultrasound detection rate of the fetuses with major anomalies was 95%, and 70% were detected in the first-trimester assessment. Four cardiac defects associated with genetic syndromes or requiring operation were included (0.31%) in this series. Two of the fetuses with cardiac defects (50%) had an increased nuchal translucency thickness. In this group, none of the fetuses with karyotype anomalies was born alive. CONCLUSIONS: The first-trimester scan is important in routine antenatal care for early detection of fetal defects, and determination of the fetuses at risk of cardiac anomalies and genetic syndromes.     

Retrieval of zona-free immature oocytes in a woman with recurrent empty follicle syndrome: a case report

BACKGROUND: Different ovulation trigger methods such as gonadotropin releasing hormone-agonist (GnRH-a) and recombinant human chorionic gonadotropin (r-hCG) plus rescue oocyte retrieval might reveal oocytes in patients with recurrent empty follicle syndrome. CASE: Endogenous luteinizing hormone was triggered with a GnRH-a (Buserelin [Suprefact pro-injection, Aventis-Pharma, Turkey], 250 microg subcutaneously) in a GnRH antagonist (Cetrorelix [Cetrotide 0.25, SeronoTurkey], 0.25 mg/d, starting on day 6), down-regulated cycle. At the first scheduled retrieval, 3 cumulus-oocytecorona complexes were recovered from the left ovary. During chemical denudation with hyaluronidase, 2 of them underwent lysis. The third was a zona-free, germinalvesicle-stage oocyte after mechanical denudation. Oocyte pickup was stopped, and recombinant human chorionic gonadotropin (hCG) (250 microg subcutaneously) was injected. Five cumulus-oocyte-corona complexes were retrieved from the right ovary 24 hours after rescue with recombinant hCG. Only mechanical denudation was done, and 4 zona-free oocytes with germinal vesicle breakdown were seen. All oocytes underwent intracytoplasmic sperm injection, and none of them were fertilized. CONCLUSION: Oocyte maturation defects should be included in etiologic mechanisms for counseling patients with empty follicle syndrome.