Genetic and epigenetic of medullary thyroid cancer

Medullary thyroid carcinoma [MTC] is an infrequent calcitonin-producing neuroendocrine tumor that initiates from the parafollicular C cells of the thyroid gland. Several genetic and epigenetic alterations are collaterally responsible for medullary thyroid carcinogenesis. In this review article, we shed light on all the genetic and epigenetic hallmarks of MTC. From the genetic perspective, RET, HRAS, and KRAS are the most important genes that are characterized in MTC. From the epigenetic perspective, Ras-association domain family member 1A, telomerase reverse transcriptase promoter methylations, overexpression of histone methyltransferases, EZH2 and SMYD3, and wide ranging increase and decrease in non-coding RNAs can be responsible for medullary thyroid carcinogenesis

Lack of BRAF-V600E mutation in stage I and II of colorectal cancer

Aim: We aimed to explore the frequency of BRAF V600E mutation in Iranian patients with colorectal cancer [CRC] as well as its association with clinic pathological characteristic of patients

Background: CRC is the third leading cause of cancer related death. There is a growing body of data showing the association of BRAF V600E mutation with malignant transformation and clinical outcome of different tumors, including CRC. These findings suggest that BRAF V600E mutation can be used as diagnostic and/or prognostic biomarker for management of cancer patients

Patients and methods: A total of 85 patients with sporadic tumor were recruited. Braf V600E mutation was investigated using sequencing of extracted DNAs from formalin-fixed paraffin-embedded [FFPE] tumor tissues. Electropherograms were analyzed using Laser-gene 6 software

Results: More than 95% of patients were in stage I and II and none of them were in stage IV. Patients were mostly below 55 years old and tumors were dominantly located in the distal colon. Of note, no BRAF V600E mutations were detected in our population

Conclusion: Our results showed no V600E mutation in the BRAF gene in stage I and II of CRC patients. Further studies in multi-center settings are warranted to examine the prognostic and/or predictive value of this marker in different stages of colorectal cancer patients

investigation of effects of blood exchange transfusion on selenium in newborn infants by instrumental neutron activation analysis method

The evidence for the effects of blood exchange transfusion on selenium [Se] in newborn infants is unknown. This study was conducted to determine the possible effects of blood exchange transfusion on Se by comparing the Se blood concentrations before and after exchange transfusion in jaundiced neonates. A total of 30 jaundiced term neonates who underwent blood exchange transfusion [EXT] for first time because of idiopathic unconjugated hyperbilirubinemia, were recruited. The Se level of 30 blood bank donors' samples used for EXT were measured and 30 pairs of uncontaminated umbilical cord blood samples were investigated for Se before and after exchange transfusion. The samples were analyzed by instrumental neutron activation analysis method. Serum bilirubin concentrations were measured by venous blood samples before EXT. The average of Se concentration before EXT was higher than that after EXT [629.78 +/- 283.82 SD ppb versus 454.83 +/- 213.75 SD ppb] [P<0.05]. There was significant correlation between the blood concentration of Se before and after EXT and also between the blood level of Se before EXT and total serum bilirubin level [P<0.05]. There was no significant correlation between the blood concentration of Se before EXT and babies' gender and weight [P>0.05]. The average Se level in samples obtained from transfused blood products was 507.90 +/- 223.56 SD ppb. Blood exchange transfusion caused a 28% decrease of the blood Se level because the blood donors had lower blood Se levels than the newborns. Furthermore, there was a significant correlation between the blood level of Se before EXT and the total serum bilirubin level

Nephrocalcinosis in newborns: a case report

Nephrolithiasis and nephrocalcinosis are common in both term and premature infants who have had difficult neonatal courses. Multiple factors may contribute and being born from a diabetic mother Is one of them. This case is about a neonate with nephrocalcinosis she is followed to 9months and remained healthy during a 9 month follow up

Acute bilirubin encephalopathy in healthy term neonates requiring exchange transfusion

There is a growing concern about an increasing bilirubin-induced neurological dysfunction [BIND] in healthy term neonates with no evidence of hemolytic disease or other risk factors. This study was done to determine the incidence of BIND in otherwise healthy, breast-fed newborn term infants without hemolysis who underwent exchange transfusion. This study was conducted in jaundiced newborn infants <7 days of age, from April 2005 to April 2007. The infants were selected if they underwent double volume exchange transfusion [ET] in the first week of life. Babies with any condition affecting neurodevelopment were excluded. Data obtained by clinical findings, and predetermined laboratory tests, and questionnaires. Infants with suspected bilirubin associated brain damage were reviewed according to findings. During the 2- year period, 140 term newborn infants underwent ET; 7 of these patients were excluded; 133 patients were followed and 69 patients were selected without BIND, and 64 were assigned to the group with BIND. This study showed that 48% of jaundiced newborn infants who underwent exchange transfusion, manifested bilirubin induced neurological dysfunction. Unsuccessful breast feeding was found to be a statistically significant risk factor for BIND [p:0.001], sex, route of delivery, family history of jaundice, mean maternal age, number of gravity, parity, abortion, and babies mean admission age ,mean age at jaundice presentation, amount of weight loss, mean total serum bilirubin level were not found to significantly influence BIND. Of the healthy term neonates who developed jaundice within the first week of life, 48% without hemolysis who underwent exchange transfusion demonstrated BIND. It is still not clear whether acute bilirubin encephalopathy affects neurodevelopmental outcome or not. Unsuccessful breast feeding was found to be a statistically significant risk factor

ABO hemolytic disease leading to hyperbilirubinemia in term newborns: value of immunohematological tests

ABO hemolytic disease of the newborn is most common cause of neonatal jaundice; previous studies have shown a poor correlation between serologic tests and clinical course in affected infants. The aim of this study was to identify the value of direct and indirect Coombs' immunohematological tests, to identify the incidence of hemolytic disease in newborns [ABO-HDN]. This two-year retrospective study of 1800 jaundiced term-neonates studied 355 cases due to ABO incompatibility divided into two groups: with and without hemolytic disease. Relation of laboratory parameters and immunohematological tests to severity of disease were studied. We did not analyze the maternal antibody titer or elusion test, and this was a limitation of the study. In this study, 355 [19.7%] of all jaundiced newborn infants were ABO incompatibles; 98 [27.6%] of the newborns who had ABO incompatibility showed ABO-HDN [5.4% of total icteric patients]. The positive direct antiglobulin [direct Coombs' test] and indirect antiglobulin [indirect Coombs' test] were diagnostic in 18.2% and 25.5% respectively in affected infants. The overall prevalence of immunohematological tests associated with ABO-HDN was 43.7%. There was significant correlation between positive antiglobulin tests and severity of jaundice [P=0.000]; also there was a significant difference between indirect and direct Coombs' test and severity of jaundice [P= 0.002]. The antiglobulin tests, namely the indirect Coombs' [IC] test and direct Coombs' [DC] test are very useful to detect the newborns liable to serious jaundice

Prevalence of portal vein thrombosis following umbilical catheterization in neonatal period

Portal venous thrombosis [PVT] is one of the most common causes of extrahepatic portal hypertension in children that may be occurring following umbilical venous cauterization or omphalities during neonatal period. We investigated the effects of umbilical cauterization during neonatal period on portal vein thrombosis. This study investigated the frequency of thrombosis of portal vein in term or preterm infants following umbilical catheterization by color doppler ultrasound. Fifty neonates who had age range [3.6+ 8days] and birth weights 1250- 4230 gram were recruited for this study and umbilical venous catheters were placed on neonates. All parents of these neonates signed a consent form. Color doppler ultrasound sonography of the portal vein was performed by two expert radiologists within 3 days following umbilical cauterization and serially for at least a period of 6 months intervals up to 3 years [6 times for each case]. Ten children were excluded from the study because of lack of follow up. Forty children completed the study. From total of 40 subjects, portal vein thromboses were detected in two children [1 girl, 1 boy] with age 2.5 and 1.5 years respectively. In these two children, other clinical signs of portal vein thrombosis manifested such as esophageal and stomach varices and splenomegaly confirmed by endoscopy. In all the other children, the physical examinations and ultrasounds were normal during 6 stages. It is recommended that care be exercised during cauterization placement in order to prevent thrombosis of the portal vein from occurring

[ effect of o6-methyl guanine methyl teranferase in colorectal cancer]

Sporadic colorectal cancer is the fourth most common cancer in Iran. The DNA repair protein O6- methylguanine-DNA methyltransferase [MGMT] is involved in the cellular defense against alkylating agents. Genetic alterations in the MGMT gene may impair the protein's ability to remove alkyl groups from the O6-position of guanine, thereby raising the mutation rate and increasing the risk of sporadic colorectal cancer. We hypothesized that amino acid substitution polymorphisms in the MGMT gene may be associated with the genetic susceptibility to sporadic colorectal cancer. We assessed five non-synomymous polymorphisms [Pro58Ser, Leu84Phe, Arg128Gln, Ile143Val, Gly160Arg] in the MGMT gene by PCR/Pyrosequencing. The population studied consisted of 200 sporadic colorectal cancer patients and 200 healthy individuals [blood donors], all of Iranian origin. Allele frequencies and genotypes were compared between the two groups. Odds ratios were calculated and the interactions among the polymorphisms, age and sex were examined. There was a significant association between two amino acid substitution polymorphisms [Arg128Gln and Gly160Arg] of MGMT gene and sporadic colorectal cancer. We could show a significant association between the two polymorphisms and colorectal cancer. This might be a superior marker for colon cancer screening in the future

Congenital embryonal rhabdomyosarcoma with prenatal onset

Rhabdomyosarcoma [RMS] is the single most common type of soft tissue sarcoma in children and adolescents but it is extraordinarily rare in neonates. Extremity RMS comprises 20% of all sites, occurs more commonly in the leg than in the arm and accounts for 9% of all RMS cases. According to our review, this is the second case of RMS on day one of life with congenital, antenatal feature, and postnatal progressive clinical course of a large tumor of the hand [pretreatment staging T2bN1M0] with embryonic histological subtype and unfavorable prognosis. The patient is a term newborn boy with huge mass in the right hand and palpable lymph node in subaxillar region. Congenital embryonal rhabdomyosarcoma is a rare form of sarcomas with congenital in nature, antenatal feature and post natal progressive clinical course of sarcomas of extremities in newborn infants

Retinopathy of prematurity among 1000-2000 gram birth weight newborn infants

The goal of this study was to identify the risk factors of retinopathy of prematurity [ROP] in neonatal intensive care unit in preterm infants born with birth weight 1000-2000g or at gestational age less than 34 weeks. From August 2000 to December 2001, 50 preterm newborn infants with birth weights less than 2000 g or gestational age less than 34 weeks admitted to the NICU were studied. Newborn infants with birth weight between 1200-2000g who received more than 6 hours oxygen and newborn infants with birth weight 1000-1200 g regardless of oxygen therapy, who survived until 4 weeks postnatal, were enrolled and followed. Patients underwent indirect ophthalmologic examination by two ophthalmologists between 4-8 weeks post partum. The newborn infants who had ROP were assigned to case group and those without ROP to control group, both groups were reexamined every 2-4 weeks or according to international classification of retinopathy of prematurity [ICROP] advice Fifty newborn infants, 36 [72%] in control group, 14 [28%] in case group, were studied. Gestational age and birth weight of the patients with ROP were significantly lower than those of control group. Duration of oxygen therapy, hyperoxia, acidosis, hypercarbia, hypocarbia and phototherapy are suggested as risk factors contributing to ROP. The results of this study demonstrate that the ROP frequency remains elevated among premature and very low birth weight infants. Infants at risk for ROP should have screening eye examinations and proper treatment

Atherosclerosis after kidney transplantation Changes of intime-media thichness of carotids during early posttransplant period

The aim of this study was to evaluate atherosclerotic changes in the carotid artery following kidney transplantation. Twenty- sis nonsmoker kidney allograft recipients who did not have cardiovascular disease or diabetes mellitus were enrolled in the study. The carotid intima-media thickness [IMT] was measured at 12 points using the patient's IMT. We followed the patients and changes in the carotid IMT were evaluated every 2 months up to the 6 th posttransplant month. The mean age of the patients at transplantation was 41.5 +/- 11.1 years. The mean baseline IMT was 0.84 +/- 0.22 mm. During the follow-up period it reached 0.85 +/- 0.22mm, 0.87 +/- 0.23 mm [P=0.1], and 0.88 +/- 0.24 mm /[P=.002] after 2, 4, and 6 months, respectively. The IMT measures significantly correlated stroke and 0.82 mm for MI, we found that 57.7% and 68% of the patients were at the risk of stroke at baseline and 6 months after transplantation [P<.001]. Also, 46.2% of the patients were at the risk of MI at baseline that rose to 53.8% at the end of the study [P<.001]. Atherosclerosis is an early event after kidney transplantation even in asymptomatic patients and those without major risk factors such as cardiovascular disease, diabetes mellitus, and smoking. Early diagnosis and treatment of atherosclerosis is of utmost importance

Maternal and other risk factors including bovine IgG in developing infantile colic

Infantile colic is one of the most current problems in the first few months of life. It is suggested that organic or psychologic and behavioral factors can predispose to involve this disorder. Here, we have studied the role of some maternal risk factors including bovine IgG levels in breast milk for appearing the colic in young babies. This retrospective study was performed on 50 infants as case group and 30 infants aged 3 weeks to 3 months who had normal growth and development as control group for one year in Mashad. Data was analyzed with Pearson Chi-Square and Fisher's exact tests. Most colicky infants were male [62% vs 38% female]. They were mainly symptomatic at neonatal period. In 64% of cases, it occurred in the first offspring. Infantile colic was more common in babies who delivered normally than by cesarean section and in mothers aged 20-30 years. According to our finding, there was no relationship between bovine IgG in breast milk and infantile colic. It revealed that anxious pregnant women had more colicky babies and paternal smoking seemed to develop colic in young infants. In order to reduce the occurrence of colic in infants, primigravid mothers aged 20-30 years should have a stressfree environment especially during pregnancy and no smoking exposure in this period

[Home phototherapy; an alternative method for treatment of jaundice in healthy-term newborns]

Hyperbilirubinemia in the healthy, term neonate is the most common cause of rehospitalization. Expense, risk of nosocomial infections, separation from mother's nursing, imparting a sense of illness to the infant, and disrupting of parents' and family relationship with neonate are all unhappy drawbacks to in-hospital phototherapy. Because home phototherapy is being used in different regions of Iran, evaluation of effectiveness, benefits and complications of this method can help the physicians and parents to use home phototherapy for management of neonatal icterus. This prospective study has been done from April 2005 to February 2006 on 108 healthy full-term newborns with jaundice that visited the emergency room of the Children's Medical Center in Tehran. These newborns that had full criteria of home phototherapy are treated by standard four lamp home phototherapy after parents' acceptance. All 108 patients 48 [44%] male and 60 [56%] female with an average age of 7.1 days and average weight of 3170 gram were treated with home phototherapy in average for 33 hours. Average serum bilirubin value on entry into home phototherapy was 16.4 [14.2-18] mg/dl and 10.1 mg/dl when discontinued. The average daily decrement in bilirubin was 3.2 mg/dl/day. Parental satisfaction has been nearly 94 percent. Phototherapy-related complications were noted only in one patient hospitalized due to hyperthermia. Poor compliance was identified in five families [4.6%] who could not continue home phototherapy due to their anxiety. Hyperbilirubinemia in 2 [1.9%] patients did not respond to phototherapy due to G6PD deficiency and hypothyroidism. Home phototherapy is an effective alternative to in-hospital phototherapy for healthy full-term jaundiced newborns if performed by an expert medical team. Benefits such as low expense, continuation of mother's nursing and not imparting a sense of illness to the infant were major causes for parents' content