TET2, DNMT3A, IDH1, and JAK2 Mutation in Myeloproliferative Neoplasms in southern Iran.

Background: Five epigenetic regulator mutations are considered in myeloproliferative neoplasms (MPN) that have prognostic and therapeutic values. Objective: We aimed to evaluate these mutations in MPNs among the Iranian population. Methods: We selected 5 mutations in 4 epigenetic regulatory genes [TET2, DNMT3A, IDH1 (rs147001633&rs121913499), and JAK2)] and evaluated 130 patients with MPNs including 78 Philadelphia chromosome negative (49 ETs, 20 PVs, and 9 PMFs) and 52 Philadelphia chromosome-positive patients as well as 51 healthy controls. Results: Eight patients (6.5%) carried the DNMT3A mutation, 35 (27%) were positive for TET2 mutation and 64 (49.3%) had the JAK2V617F mutation. In the healthy controls, 16 (31.4%) cases had the TET2 mutation (15 Heterozygote + 1 Homozygote) and one had heterozygote JAK2 mutation. There was no statistically significant difference between patient groups for any of these mutations, except for JAK2. The JAK2 mutation rate was 18 (90%), 25 (51%), 7 (77.8%), 14 (26.9%) in polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic myelocytic leukemia, respectively. Patients aged 60 and older were more likely to carry the TET2 mutation (23% vs. 39% in younger and older than 60 years old individuals, p=0.025). IDH1 was not detected at all and PV had the highest TET2 mutation 7(35%). Two PMF patients had a history of bone marrow transplantation that were negative for IDH1and DNMT3A and one was positive for TET2 mutation. Conclusion: In the normal Iranian population, the heterozygote form of TET2 mutation is significant, especially in the elderly. No association was found between JAK2 and TET2 mutations. Both of them are more prevalent in the age group of 60 years and older. DNMT3A mutation has a low prevalence and occurs in both positive and negative MPNs.

Chemical modifications and their effects on gluten protein: An extensive review.

Gluten protein as one of the plant resources is susceptible to genetic, physical, chemical, enzymatic and engineering modifications. Chemical modifications have myriad advantages over other treatments, including short reaction times, low cost, no requirement for specialized equipment, and highly clear modification effects. Therefore, chemical modification of gluten can be mainly conducted via acylation, glycosylation, phosphorylation, and deamidation. The present review investigated the impact of different chemical compounds on conformations of gluten and its subunits. Moreover, their effects on the physico-chemical, morphological, and rheological properties of gluten and their subunits were studied. This allows for the use of gluten for a variety of purposes in the food and non-food industry.

Quantification of Active and Latent Form of Human Cytomegalovirus Infection in Umbilical Cord Blood Donors by Real-Time PCR.

BACKGROUND: Umbilical cord blood (UCB) is believed to be a highly valuable source of hematopoietic stem cells for transplantation. Objective: To investigate the prevalence of active and latent human cytomegalovirus (CMV) infection in UCB donors in Iranian population. METHODS: A total of 825 UCB samples was collected under standard procedures and analyzed for the presence of CMV DNAs in buffy coat (latent infection) and plasma (active infection). DNA was extracted from buffy coat and plasma samples separately and tested with quantitative real-time PCR. All positive samples were checked by ELISA for IgG and IgM anti-CMV antibody. RESULTS: Latent CMV infection was detected in 17 (2%) buffy coat samples with a low level of viral load, which indicated the presence of latent viral infection in donors. None of the plasma samples were found positive for CMV DNA reflecting no active infection. In the 17 positive samples, CMV viral load was 91-104 (mean: 100) copies/mL. All samples positive for viral DNA were also found positive for CMV IgG antibody by ELISA. No CMV IgM antibody was detected in positive samples. CONCLUSION: CMV is still the most important virus that infects hematopoietic stem cells and could be dangerous, especially for immunocompromized transplant recipients. We therefore suggest using real-time PCR for the detection and quantification of the viral DNA in buffy coat and plasma of UCB donors. PCR of plasma for detection of CMV and antibody assay for CMV infection add no more sensitivity for the detection of latent CMV infection in UCB donors.

Quantitative polymerase chain reaction for detection of human herpesvirus-7 infection in umbilical cord blood donors.

OBJECTIVE: Umbilical cord blood (UCB) has been a reasonable alternative to granulocyte colony-stimulating factor-mobilized peripheral blood or bone marrow, as a source of hematopoietic stem cells with a lower risk of graft-versus-host disease. In immunocompromised hosts after transplantation, the risk of viral infection in adults, especially with beta-herpesviruses such as human herpesvirus-7 (HHV-7), may be increased. This virus in immunocompromised patients can be reactivated from latency and converted to an active phase. Therefore, light-upon-extension real-time polymerase chain reaction (PCR) was developed to assess the prevalence and load of HHV-7 in the plasma and buffy coat of donors. METHODS: About 825 UCB samples under standard protocol from donors were collected. Then, DNA from plasma and buffy coat was extracted and quantitative real-time PCR was performed with light-upon-extension primers. RESULTS: Overall, HHV-7 was detected in 3.64% (30/825) of UCB donors. HHV-7 DNA was detected in 26 (3.2%) buffy coat samples (latent infection), and only 4 (0.48%) of them were positive for HHV-7 DNA in plasma samples (active infection); the mean HHV-7 viral load was 1.31 × 10(1) copies/mL in latent infection, and 1.94 × 10(5) copies/mL in active infection. CONCLUSIONS: We suggest that real-time PCR in plasma and buffy coat could be a useful method to detect active and latent HHV-7 infection in UCB donors and determine its role in subsequent transmission events.

Fine needle aspiration cytology of palatine tonsils: a study of 112 consecutive adult tonsillectomies.

OBJECTIVE: To study fine needle aspiration cytology (FNAC) findings of tonsillar lesions with histological controls and to assess its role in the diagnostic evaluation of tonsillectomy specimens. METHODS: This study consisted of 112 cases that required tonsillectomy, comprising 55 (49.1%) men and 57 (50.9%) women. The ages ranged between 20 and 62 years. The clinical diagnosis in 101 cases was chronic tonsillitis, whereas 11 were suspected of neoplasia. FNAC was performed before tonsillectomy under general or local anaesthesia or on fresh specimens using a 21-G needle. The smears were stained using Wright-Giemsa and Papanicolaou methods. Histological examination was carried out on surgical specimens of all cases and, when required, immunohistochemistry was performed on histological sections. The diagnostic outcomes between FNAC and surgical biopsy were compared. RESULTS: In this study, 106 cases were diagnosed as chronic tonsillitis/follicular hyperplasia, four cases as non-Hodgkin's lymphoma, one as Hodgkin's lymphoma and one as monophasic synovial sarcoma. All malignant cases were diagnosed by FNAC, but synovial sarcoma was incorrectly diagnosed as squamous cell carcinoma. Five cases clinically suspected of neoplasia were correctly diagnosed as chronic tonsillitis on cytology. CONCLUSION: Tonsillar aspiration is a safe procedure and is useful in the evaluation of tonsillectomy specimens. However, ancillary tests on cytological material are often needed when neoplasia is suspected and would help clinical management and allow histological examination of cases diagnosed cytologically as lymphoma.

Rheumatoid arthritis of the larynx: the importance of early diagnosis and corticosteroid therapy.

Rheumatoid arthritis is a destructive systemic disorder characterized by remissions and exacerbations. The larynx is involved in approximately 25% of these patients. The importance of early detection of laryngeal involvement by this disease and treatment with corticosteroids has not been adequately addressed in the literature. We have described five patients who had early diagnosis and successful treatment with systemic corticosteroids and/or corticosteroid injection of the cricoarytenoid joint.

Chronic otitis media: surgical failures and management.

Failure of primary tympanomastoid surgery to control chronic otitis is a difficult otologic problem. The facial nerve, middle fossa dura, and inner ear structures are at high risk because of distorted anatomy from the primary surgery and/or recurrent disease. In this article our techniques and experience with 42 revision procedures for recurrent chronic otitis with and without cholesteatoma are presented. Control of otorrhea and/or cholesteatoma was achieved in 93% of the cases; however, this might be less after 5 years of follow-up. The mean postoperative air-bone gap was 25 dB, and this is a 6 dB improvement from the preoperative level. Revision tympanomastoid surgery was very effective and safe in the management of this difficult problem. For cholesteatoma in particular, the canal wall down technique is our procedure of choice.

Paralysis of the recurrent laryngeal nerve by an extracapsular thyroid adenoma.

We treated a patient with an ectopic thyroid adenoma that caused recurrent laryngeal nerve paralysis and upper aerodigestive tract compression. After excision of the mass and release of the compressed recurrent nerve, the true vocal cord function returned almost to normal. We review the literature, diagnosis, and management of thyroid disease associated with vocal cord paralysis.

External ear canal cholesteatoma.

External ear canal cholesteatoma (EECC) is a rare otologic entity. Erosion of the inferior canal wall and accumulation of keratin debris are consistent findings. In the past there had been confusion between EECC and keratosis obturans, and they were thought to represent the same disease process. Currently, based on clinical and pathologic findings, it is believed that they are two different entities. In this article we present our experience in treating eight patients with EECC. For limited lesions, local debridement and curettage of necrotic bone is effective management. For more extensive lesions, canalplasty or tympanomastoidectomy is indicated.

Coexisting otosclerosis and Ménière's disease: a diagnostic and therapeutic dilemma.

The coexistence of otosclerosis and Meniere's disease is well documented; however, otosclerosis may not be recognized in patients presenting mainly with Meniere's symptoms and, therefore, treatment may not be effective. In this paper, eight patients with otosclerosis and Meniere's disease are presented. The diagnosis of coexisting otosclerosis and Meniere's was initially missed in most of these patients. Medical and surgical treatment had been unsuccessful. Diagnostic and therapeutic guidelines for management of these patients are discussed. Our preliminary conclusions are: 1. otosclerosis should be diagnosed in patients with Meniere's disease, especially when bilateral or when suggested by clinical and/or laboratory findings, and 2. the addition of sodium fluoride to diet-diuretic management of such patients appears effective.

Bilateral peritonsillar abscesses and quinsy tonsillectomy.

Two patients presented with history, symptoms, and clinical findings suggesting unilateral peritonsillar abscesses. At the time of quinsy tonsillectomy, the patients were found to have pus present in the contralateral peritonsillar spaces. These findings prompted a review of the literature to determine the actual frequency of bilateral peritonsillar abscesses and to reassess the approach to treatment of patients presenting with peritonsillar abscesses.Peritonsillar abscess frequently develops following the onset of acute tonsillitis, and it is possible that this process occurs bilaterally with the developmental stages of the abscesses being different on each side. Intensive antibiotic treatment, incision and drainage of the obvious abscess probably suppresses the development of and masks the presence of the abscess on the opposite side.Quinsy tonsillectomy has been indicated previously for patients not responding to intravenous antibiotic treatment and incision and drainage of their peritonsillar abscess. The possibility of a subclinical contralateral peritonsillar abscess being present is an additional indication for proceeding with a quinsy tonsillectomy, especially in patients who remain febrile after apparent satisfactory drainage of the clinically evident abscess.

Otologic symptoms and findings of the pseudotumor cerebri syndrome: a preliminary report.

Pseudotumor cerebri or benign intracranial hypertension is a syndrome characterized by increased intracranial pressure without focal signs of neurologic dysfunction. The clinical manifestations of this syndrome are usually headache and/or disturbance of vision. Although tinnitus, hearing loss, and vertigo have been described in association with intracranial hypertension, otologic symptomatology as the presenting manifestation of this syndrome has not been previously reported. In this article we report the otologic symptoms and findings of two pseudotumor cerebri patients, one of whom presented with pulsatile tinnitus. The pathogenesis of the otologic symptoms, diagnostic workup, and management of these patients are discussed.

Brain-stem evoked response waveform variation associated with recurrent otitis media.

Two cases suggest that long-standing recurrent otitis media contributes to delayed brain-stem evoked response wave III and V latencies persisting after resolution of the otitis media. The persistence of the delayed waves may not reflect structural damage, but rather may still reflect a slowly recovering system.

Twenty-five years' experience treating cerebro-rhino-orbital mucormycosis.

Mucormycosis is an acute fungal disease with high mortality exhibiting craniofacial, pulmonary, cutaneous, gastrointestinal and disseminated forms. Cerebro-rhino-orbital (CRO) mucormycosis is the type that most frequently involves the structures of the head and neck. While usually non-pathogenic, these saprophytic organisms can be particularly lethal in chronically debilitated patients. Between the years 1957 and 1982, 18 cases of CRO mucormycosis were seen at the Medical College of Virginia Hospital and the McGuire VA Medical Center. Four illustrative cases of CRO mucormycosis are presented to emphasize: the importance of clinical awareness of the disease, the necessity of tissue biopsy for diagnosis, the need of appropriate management of any underlying disorder, administration of amphotericin-B, and the performance of adequate surgery.

Epidermoid cyst of the frontal bone masquerading as frontal sinusitis.

Epidermoid cysts occur whenever two epidermal surfaces fuse together during early intrauterine life and an ectodermal implant is retained deep to the surface. They are very slow growing and symptoms may not occur till middle age. The authors present a patient whose symptoms of frontal headache were mistaken for frontal sinusitis for over 10 years. The patient's symptoms were completely relieved by surgical excision of an epidermoid cyst of the frontal bone.

Conjoint hyoid bone segments for the repair of severe laryngeal stenosis.

We discuss and show by illustrations a surgical technique for the management of severe combined laryngeal and subglottic stenosis using multiple pieces of hyoid bone. No serious problems resulted from the removal of the entire hyoid bone. All patients have maintained a good airway, despite the possibility of absorption of a free bone graft. Although it is reasonable to try to use the hyoid bone with a strap muscle pedicle, it is impossible to reconstruct the subglottic and laryngeal area without multiple pieces. Our experience encourages us to use multiple pieces of free hyoid bone for laryngotracheal reconstruction.