A decade genetic diversity in Circulating influenza B virus in Iran (2010-2019): Divergence from WHO-recommended vaccine strains.

BACKGROUND: Data on the disease burden and circulation patterns of influenza B virus lineages for Iran are limited. OBJECTIVE: This review aims to describe the pattern of influenza B occurrence in Iran, comparing it with the proposed vaccine strains and determining the match and mismatch with the prescribed vaccine annually. METHODS: Various sources were used to retrieve information of the data; such as information from an online search of databases such as FluNet, GISAID, and NCBI. After extracting protein sequence records in GISAID, sequence alignment with vaccine strain and construction of a phylogenetic tree were performed. Subsequently, categories of the registered circulating strains were evaluated for matching with the vaccine strains. RESULTS: Of the total registered influenza-positive samples, 20.21% were related to influenza B virus. The phylogenic tree was designed based on 43 samples registered in the GISAID database; 76.74 and 23.25% sequences were of Yamagata and Victoria lineages, respectively. The most prevalent influenza B virus strains circulating during the study years belonged to the Yamagata lineage. In general, the match of the influenza B virus predominant circulating strains with administrated vaccines was observed in Iran. However, a high level of mismatch between the vaccine strain and Iranian isolates was identified in 2016‒2017. CONCLUSION: The review of match and mismatch in influenza vaccine in order to improve the composition of the prescribed vaccine in each region is very important because the vaccine efficacy decreased when the strain included in vaccine did not match the circulating epidemic strain.

Electrochemical biosensing of influenza A subtype genome based on meso/macroporous cobalt (II) oxide nanoflakes-applied to human samples.

Meso/macroporous cobalt (II) oxide nanoflakes were electrodeposited in a one-step process in the presence of N-methylpyrrolidone. On the surface of nanoflakes, a specific single stranded DNA sequence from the genome of influenza A subtype was then immobilized to fabricate an electrochemical biosensor. Hybridization of the biosensor with complementary, non-complementary and base-mismatch sequences was electrochemically detected. The biosensor was also employed to detect complementary DNA of viral RNA in culture and human samples. The biosensor could detect the complementary sequence with a detection limit of 86.4 amol L-1 and a linear concentration range of 1.0 fmol L-1 to 1.0 nmol L-1. It also detected a complementary DNA sequence converted from viral RNA with a detection limit of 0.28 ng µL-1 in a linear concentration range of 0.5-10 ng µL-1. Low detection limit, simple method of preparation of the transducer and no needing any DNA strand modification and tag are the principal advantages of the biosensor.

Effects of three Commercial Mouth Rinses on the Cultured Fibroblasts: An in Vitro Study.

STATEMENT OF PROBLEMS: An ideal antimicrobial agent should have minimal cytotoxic effect to host cells. PURPOSE: The aim of this study was to determine the cytotoxic effect of three commercial mouthwashes (Chlorhexidine, Persica and Irsha) on the cultured fibroblasts. MATERIAL AND METHODS: For determining the cytotoxic effect of Irsha, Chlorhexidine and Persica, uninfected cells were grown in the absence and presence of various concentration (2,4,8,16,32,64,128) of these mouth washes for 1, 2, 3 and 4 days. RESULTS: In this study, three mouth washes show cytotoxic effect on the cultured cells, at commercially available concentration and even diluted and Irsha was found to be the most toxic one. Cytotoxicity of three mouthwashes was reduced with decreasing concentration.

Antigenic variations of human influenza virus in Shiraz, Iran.

PURPOSE: Influenza virus is a major cause of human respiratory infections and responsible for pandemics and regional outbreaks around the world. This investigation aims to determine the prevalent influenza genotypes during 2005-2007 outbreaks in Shiraz, the capital city of Fars province, southern Iran and compare the results obtained with those of previous study. MATERIALS AND METHOD: Of the 300 pharyngeal swabs collected from influenza patients, 26 were found to be positive by culture and hemagglutination (HA) assays. Typing and subtyping of the isolates carried out by using multiplex RT-PCR and phylogenetic analysis performed on isolated HA genes using neighbour-joining method. RESULT: Out of 26 positive isolates 12 and 14 were H1N1 and H3N2 respectively. The phylogenetic and amino acid sequence analyses of our H1N1 isolates showed 99-100% genetic resemblance to A/NewCaledonia/20/99 (H1N1) vaccine strain. Most of the Iranian H3N2 isolates varied form A/California/7/2004 vaccine strain in 20 amino acids of which positions 189,226 and 227 were located in antigenic sites of HA1 molecule. These substitutions were not observed in any of the H3N2 subtypes from the same region reported previously. CONCLUSION: The H3N2 subtype strains prevalent during the 2005/7 influenza outbreak in southern Iran demonstrated a drastic antigenic variation and differed from A/California/7/2004 vaccine strain. The H1N1 subtypes showed a notable resemblance to A/NewCaledonia/20/99 vaccine strain and therefore were predicted to be capable of conferring sufficient immunity against H1N1 subtypes.

Disseminated brown tumors from hyperparathyroidism masquerading as metastatic cancer: a complication of parathyroid carcinoma.

Osteitis fibrosa cystica (brown tumors) can be a skeletal manifestation of advanced hyperparathyroidism, including parathyroid cancer. Severe osteitis fibrosa cystica can mimic metastatic bone diseases especially in patients with a history of cancer. Because the treatment and prognosis of these two problems differ greatly considering hyperparathyroidism in the differential diagnosis of patients found to have osteolytic lesions is critical for the appropriate management of these patients. In this case report we describe a patient with a history of renal cell cancer and presumed osteolytic bone metastases. During prophylactic intramedullary rodding to prevent pathologic fracture of her femur she was found to have a benign lesion related to her previously undiagnosed hyperparathyroidism caused by an underlying parathyroid cancer. A detailed review of this disease and the associated bone changes is also included to underscore the importance of an adequate differential diagnosis as well as optimal management. Patients with hypercalcemia or bony lesions should not automatically be treated palliatively for metastatic disease just because of a past medical history of cancer. Hyperparathyroidism is a readily curable problem if properly diagnosed.

Characterization of Leishmania isolated in Iran: 1. Serotyping with species specific monoclonal antibodies.

A total of 156 isolates of Leishmania from patients with cutaneous leishmaniasis and one isolate from gerbil were characterized using standard monoclonal antibodies (mAb) in ELISA and IFA test systems. The geographic distribution of the isolates was 30 isolates in Shiraz, 28 in Kerman and 98 in Tehran. A total of 63, 72, and three Leishmania promastigote isolates preferentially reacted with anti-Leishmania tropica mAb (A11), anti-Leishmania major mAb (T1) and anti-Leishmania infantum mAb (D2), respectively. Of the three isolates which reacted with anti-L. infantum mAb, two were dermotropic strains of L. infantum and one was the organism isolated from gerbil. Mixed reactions with the monoclonal antibodies were also observed as six isolates reacted with both anti-L. tropica and anti-L. major mAbs, five reacted with anti-L. tropica and anti-L. infantum mAbs and two with anti-L. major and anti-L. infantum mAbs. The monoclonal antibodies used did not react with five of the isolates. The present investigation has identified the organisms from the known and newly emerged foci of cutaneous leishmaniasis in Iran.

Somatostatin analogue in treatment of coexisting glucagonoma and pancreatic pseudocyst: dissociation of responses.

After an acute episode of pancreatitis, a 63-year-old man was found to have a pancreatic glucagonoma. The tumor was resected without evidence of metastases. Three years later he had symptoms of uncontrolled diabetes, no skin lesions, and diarrhea and was found to have a pancreatic pseudocyst and multiple hepatic metastases. Glucagon concentrations were raised but were suppressible by glucose and somatostatin and responded to arginine stimulation. He was treated for 6 months with octreotide (Sandostatin), which reduced his symptoms; the pseudocyst resolved, but liver metastases continued to grow. Although spontaneous resolution of the pseudocyst is possible, this case appears to illustrate differences in sensitivity of endocrine and exocrine tissues to suppression by Sandostatin.

Transhepatic portal vein catheterization for localization of sporadic and MEN gastrinomas: a ten-year experience.

We review here the 10-year experience at the University of Michigan with 35 patients with gastrin hypersecretion who underwent transhepatic venous sampling (THVS) for tumor localization. Since 1978 THVS has been done routinely in all patients with gastrinoma syndrome considered for operation. Thirty-one patients had proved gastrinomas--21 benign sporadic tumors and 10 tumors associated with multiple endocrine neoplasia type-I (MEN I) syndrome. The correlation between the site of the maximal gradient and location of a sporadic tumor was poor. Overall sensitivity was only 35%, specificity 89%, and negative predictive value 89%. If gradients were regionalized to three areas--body and tail, gastrinoma triangle, and hepatic lobes--then sensitivity was 94%, positive predictive value 94%, and specificity 97%, with a negative predictive value of 97%. The maximal gastrin gradient above the mean for other values gave the greatest sensitivity and specificity. In MEN I syndrome, only four of eight patients with macroadenomas had their tumors correctly localized, a sensitivity of 50% and specificity and negative predictive value of 75%. In 19 patients who had operative localization of sporadic gastrinoma, computed tomography had a sensitivity of 31%, specificity of 66%, positive predictive value of 83%, and negative predictive value of 15%. Selective angiography was better, with a sensitivity of 29%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 100%. Regionalization to the triangle proved valuable for detection of microgastrinomas, as was measurement of hepatic vein gastrins for identification of intrahepatic tumors. In MEN I syndrome, if regionalization was achieved (50%), tumor resection appeared to offer hope of "cure." We conclude that THVS is the best tool for tumor regionalization to the pancreatic tail and body, gastrinoma triangle, and hepatic lobes. It has allowed us to achieve surgical cure in 19 of 21 patients with sporadic gastrinomas and improvement in four of eight patients with MEN I syndrome.

Effects of sandostatin on plasma chromogranin-A levels in neuroendocrine tumors.

We have determined the effects of Sandostatin (SMS 201-995, Sandoz) on chromogranin-A (CgA) in the blood of 14 patients with neuroendocrine tumors of the gastroenteropancreatic axis, 7 with carcinoid tumors, 5 with gastrinomas, and 1 each with a glucagonoma and tumor-secreting vasoactive intestinal peptide. Two thirds of the patients had elevated plasma CgA. Sandostatin administration suppressed CgA in 12 of the 14 patients. In 8 of 10, the clinical response to Sandostatin paralleled the reduction in CgA levels. There was a strong correlation between the change in CgA levels and the respective blood concentration of the hormone produced by the tumor. Serial measurement of CgA may provide an additional means of monitoring these tumors and their secretory activity where other measures are not available.

Treatment of endocrine tumors of the pancreas.

Many advances have been made in the recognition, diagnosis, and management of patients with functional islet cell tumors during the past three decades. Improved results should occur in those patients with functional islet cell tumors causing recognizable syndromes. The likelihood of this occurring is predicated upon an awareness, high index of suspicion, the use of immunoassays, provocative tests, and appropriate localization studies. Earlier diagnosis is providing the opportunity to cure many patients who could be treated only with palliative procedures or drugs in the past. Figure 1 summarizes the current management plan utilized in evaluating patients whose findings suggest the possibility of a functional islet cell tumor syndrome. Nonfunctional islet cell tumors continue to be a therapeutic problem because their detection (with the exception of those discovered incidentally during upper abdominal explorations, CT scanning for other indications, or CT scanning of the pancreas in MEN-1 patients) usually does not occur until the tumor is locally invasive or associated with liver metastases. The treatment of these tumors has usually been palliative, utilizing chemotherapy and medical therapy including the somatostatin analogue Sandostatin or an operation to bypass an obstruction of the biliary tract or duodenum.

Use of somatostatin analog in management of carcinoid syndrome.

Carcinoid tumors are the most frequent gut neuroendocrine tumors accounting for more than 50% of all tumors of the gastroenteropancreatic (GEP) axis. These tumors appear to derive from a stem cell line capable of differentiating into a variety of malignant cells that secrete many different peptides and amines. The symptoms of carcinoid tumors are often non-specific, vague abdominal pain that may precede the diagnosis by a median of 9 years. Carcinoid syndrome occurs in less than 10% of patients. We evaluated the effects of SMS 201-995 in 14 such patients, 12 with diarrhea, 8 with flushing, 3 with wheezing, one with tricuspid valve incompetence, 6 with facial telangiectasia, 3 with a pellagra type dermatosis and one with myopathy. Diarrhea was abolished or significantly reduced in 83%, flushing in 100%, wheezing in 100%, and myopathy improved in the one patient. Blood serotonin was resistant to change, urine 5HIAA fell in 75%, and most gut neuropeptide hormones apart from somatostatin were suppressed. Tumor growth appeared to be slowed in 2/3 of cases treated for up to 4 years. The analog of somatostatin appears to be a useful addition to the therapeutic armamentarium for carcinoid tumors and the symptom complex.

Clinical features of carcinoid syndrome and the use of somatostatin analogue in its management.

A review is given on the clinical features of carcinoid syndrome including symptomatology, diagnostics, biochemistry and treatment. We have reviewed the literature on current therapy of carcinoid patients with special emphasis on the use of the somatostatin analogue SMS 20-1995. In addition, we present data on the effects of SMS 201-995 on indices of a clinical, biochemical and tumor growth. Diarrhea is abolished or significantly reduced in 75% of patients, flushing improves in 100%, wheezing in 100% with a decrease in airways resistance, and in one patient myopathy has improved. Blood serotonin is notoriously resistant to intervention and urinary 5-HIAA will decrease in 75% of causes but subsequently rebounds in 38%. Tumors, in general, continue to grow, but this may be slowed or in rare cases tumor growth is arrested. In individual instances the tumor may even infarct, leading to spontaneous cure. Tumors secreting PP, ACTH and calcitonin may be particularly resistant to treatment, whereas VIP secreting tumors appear to be sensitive.

Distinguishing features of idiopathic flushing and carcinoid syndrome.

We compared the clinical and biochemical profiles of 11 patients with idiopathic flushing (IF) with those of eight patients with carcinoid syndrome (CS). Patients with IF were more often women, had a longer duration of symptoms, and were younger. Palpitations, syncope, and hypotension occurred only in patients with IF, while wheezing and abdominal pain occurred only with CS; diarrhea occurred in both types of patients. Elevated blood serotonin levels were present primarily in CS. Increased levels of urine 5-hydroxyindoleacetic acid was specific for CS but unsufficiently sensitive to detect all cases. Abnormalities of gut and vasoactive peptides failed to distinguish the two conditions. Flushing in carcinoid patients responds uniformly to octreotide (Sandostatin), but only one third of the patients with IF are relieved of the symptom. Patients with IF have features that distinguish them from individuals with flushing from other causes, such as CS, postmenopausal state, chlorpropamide-alcohol flush, panic attacks, medullary thyroid carcinoma, and autonomic epilepsy. Familiarity with the clinical and biochemical features of IF should facilitate evaluation and identification of these patients.

Somatostatin analogue (SMS 201-995) in patients with gastrinomas.

We have examined the effects of the somatostatin analogue (SMS 201-995) in 10 patients with gastrinoma syndrome. Four had hepatic metastases, one had a tumor in a peripancreatic lymph node, two had resectable intrahepatic and intraduodenal gastrinomas, and in three the primary tumor was not found. Acutely, SMS 201-995 decreased acid secretion and restored the BAO/MAO ratio to normal in eight of eight patients. Basal and secretin-stimulated gastrin responses were suppressed but not normalized in eight of eight patients. Suppression of endogenous gastrin restored responsiveness to exogenous gastrin. Treatment for up to 12 months with SMS 201-995 controlled symptoms in six of eight patients, suppressed serum gastrin in three of five, and suppressed acid secretion in three of three patients. Treatment with SMS 201-995 in three patients for 5 months decreased tumor secretion of gastrin and diminished basal acid secretion, an effect that persisted in two of three patients 48 hours after withdrawal of SMS. In patients with metastatic disease who had high levels of gastrin, SMS treatment for 5 to 12 months did not inhibit tumor growth or decrease gastrin levels. SMS treatment arrested progression of tumor growth only in patients who had a reduction in gastrin and gastric acid secretion. We conclude that SMS may be useful in the management of gastrinoma patients by decreasing hypersecretion of gastrin and gastric acid and, over a longer term, may even change tumor capacity to release gastrin and gastric acid secretion. SMS may thus be useful as a palliative agent and as an adjunct to conventional treatment of the gastrinoma syndrome. SMS does not appear to shrink tumor mass in patients with very high basal gastrin levels.

Somatostatinomas, PPomas, neurotensinomas.

We have reviewed data pertinent to three tumor syndromes that derive from overproduction of three GEP peptide hormones. The clinical syndrome of somatostatin excess remains well defined with diabetes, diarrhea, steatorrhea being predominant features. With the availability of assays and increasing awareness, more cases are being diagnosed in the intestine and these differ somewhat in their presentation with cholecystitis, GI bleeding, or a mass as the cardinal features. An unusual association with MEN II pheochromacytoma and neurofibromatosis is emerging. PPomas remain enigmatic. Although diarrhea is a feature, these tumors are usually silent and present with hypatomegally, abdominal pain, and jaundice because of the large size and malignant nature. Neurotensinomas remain rare and truly difficult to separate from the symptom complex produced by VIP excess. Edema, hypotension, cyanosis and flushing should alert one to the possibility of a neurotensin-secreting tumor.

Somatostatin analogue (SMS 201-995) in the management of gastroenteropancreatic tumors and diarrhea syndromes.

SMS 201-995 (Sandostatin) was studied using low doses (50 to 100 micrograms) administered subcutaneously every 12 hours. A single 50-micrograms dose of SMS 201-995 effectively controlled gastric acid and blood gastrin levels for 12 hours in three patients with benign gastrinomas and was useful in their perioperative management. Higher doses of the agent (500 to 800 micrograms per day) had no effect on metastases in one of two patients with metastatic gastrinoma. In the other patient, one tumor shrank but the other continued to grow after three months of treatment while serum gastrin levels did not change. Cultured metastatic tumor tissue from this patient released different forms of gastrin; growth rates varied, independent of uptake of SMS 201-995, and gastrin release increased. A neonate with nesidioblastosis maintained normal blood glucose levels while receiving SMS 201-995 therapy following a 95 percent pancreatic resection. In two elderly patients with organic hypoglycemia--one with a single benign adenoma and one with multiple adenomatosis--the somatostatin analogue did not prolong the hypoglycemia-free interval. In nine patients with carcinoid syndrome, flushing was uniformly controlled with 50 micrograms of SMS 201-995 administered every eight to 12 hours. One of the nine required exocrine pancreatic replacement. After six months of treatment, three of the nine had no change in tumor size and one had remission of symptoms and stopped treatment. In two patients with vipoma, SMS 201-995 controlled diarrhea and reduced levels of vasoactive intestinal peptide; tumor necrosis occurred in one patient. In a patient with diabetic diarrhea unresponsive to all treatments, SMS 201-995 therapy controlled the diarrhea but did not interfere with control of the diabetes.