Spectrum of molecular alterations in colorectal, upper urinary tract, endocervical, and renal carcinomas arising in a patient with hereditary non-polyposis colorectal cancer

Hereditary nonpolyposis colon cancer (HNPCC) syndrome is the most frequent hereditary cancer syndrome predisposing to cancers of various locations, especially colon, endometrium, stomach, and upper urinary tract. Carcinomas of the kidney parenchyma are not considered as an HNPCC-related tumor. HNPCC tumors are characterized by microsatellite instability (MSI) due to a defect in mismatch repair (MMR) and carry somatic frameshift mutations in mononucleotide repeats within the coding regions of key genes. We report the first case of a papillary carcinoma of the kidney in an HNPCC patient who developed carcinomas of the upper urinary tract, endocervix, and colon. Whereas the HNPCC-related tumors demonstrated MSI phenotype, loss of MSH2 protein expression, and frameshift mutations in several of the 13 target genes analyzed, the kidney cancer displayed MSS phenotype, normal MMR protein expression, and no frameshift mutation in target genes. Our observations do not support the possibility that papillary carcinomas are part of HNPCC syndrome.     

Patterns and role of diversifying selection in the evolution of Toxoplasma gondii SAG5 locus

The higher intergenotypic polymorphism of the surface antigen genes 5 (SAG5)A, SAG5C, and SAG5E in Toxoplasma gondii was proposed to be the outcome of positive selection pressure favoring variation within these loci. However, the exact nature and magnitude of this selection is not completely known. To address this issue, the amino acids on which natural selection may operate were identified by comparing the ratios of nonsynonymous and synonymous substitutions (p _N/ p _S) of homologous DNA sequences in strains belonging to the three major genotypes of T. gondii. Both positive and negative selections were detected and are likely to have contributed to shaping the patterns of nucleotide substitution and polymorphism in SAG5 genes. Several sites identified in SAG5 loci as likely to be under positive selection suggesting that diversifying selection may have promoted divergence in these genes. Also, it was noted that the SAG5 genetic loci contain many areas that exhibit signs of purifying selection; some of these areas might be the attractive candidates for drug targets. Phylogenetic analysis using the neighbor-joining and maximum parsimony methods grouped the SAG5 sequences of T. gondii strains into three distinct statistically well-supported evolutionary lineages. These findings carry important implications for human and veterinary toxoplasmosis epidemiology and may provide important insights into the pathways through which virulence has evolved in T. gondii.     

Purification of<Emphasis Type="Italic"> Sarcocystis neurona</Emphasis> sporocysts from opossum (<Emphasis Type="Italic">Didelphis virginiana)</Emphasis> using potassium bromide discontinuous density gradient centrifugation

This report describes a new, inexpensive procedure for the rapid and efficient purification of Sarcocystis neurona sporocysts from opossum small intestine. S. neurona sporocysts were purified using a discontinuous potassium bromide density gradient. The procedure provides a source of sporocyst wall and sporozoites required for reliable biochemical characterization and for immunological studies directed at characterizing antigens responsible for immunological responses by the host. The examined isolates were identified as S. neurona using random amplified polymorphic DNA primers and restriction endonuclease digestion assays. This method allows the collection of large numbers of highly purified S. neurona sporocysts without loss of sporocyst viability as indicated by propidium iodide permeability and cell culture infectivity assays. In addition, this technique might also be used for sporocyst purification of other Sarcocystis spp.     

Pregnancy and delivery with an intrauterine device in situ: outcomes in the National Inpatient Sample Database

Background: Pregnancy with intrauterine device in place is rare and there are limited data that exist regarding associated perinatal outcomes.

Objective: The objective of this study is to determine the association between presence of an intrauterine device during pregnancy and spontaneous abortion, induced abortion, and preterm or small for gestational age delivery outcomes.

Study design: The National Inpatient Sample database was analyzed for the years 2010 and 2011. Maternal records with an intrauterine device in situ during delivery were identified using International Classification of Diseases, Ninth Revision, diagnostic codes. Primary outcome was incidence of spontaneous abortion. Secondary outcomes were incidence of induced abortion, preterm delivery, and small for gestational age. Data were analyzed using Chi-square and Fisher’s exact tests to calculate odds ratios (ORs) of abortion in association with intrauterine device in situ during pregnancy. Maternal birth records were further analyzed for adverse neonatal outcomes using logistic regression models, controlling for possible confounding variables.

Results: The data included 8,597,284 maternal birth records; 0.02% with an intrauterine device in situ. Patients with an intrauterine device in situ experienced a higher frequency of the pregnancy ending in spontaneous abortion (OR: 7.15; 95% confidence interval (CI): 5.06–10.09; p?p?in situ was 2.04 (95% CI: 1.71–2.43; p?p?=?.022), after controlling for associated demographic and clinical variables.

Conclusion: The presence of an intrauterine device in situ during pregnancy was associated with increased spontaneous and induced abortions, and increased incidence of delivery of a preterm, but not small for gestational age infant.     

Reversed rotation of the midgut in adults – a case report

Intestinal obstruction is a common surgical emergency. It is often due to adhesions; however, when the patient is young and has a virgin abdomen, we have to consider uncommon causes. We present a rare case of reversed rotation of the midgut as a cause for intestinal obstruction.     

Is it a safe practice to administer oxygen during uncomplicated delivery: A randomized controlled trial?

Background

Newborns exposed to oxygen suffer from an oxidative stress with significant alterations in the concentrations of superoxide dismutase (SOD) and glutathione (GSSG).

Objective

To investigate the biological and clinical effects of oxygen administration to delivering mothers.

Methods

We conducted a randomized, double-blinded, controlled trial on a cohort of delivering women (n = 56) with an uncomplicated term pregnancy. Women were randomly assigned to one of two groups: Oxygen group or Room Air group. The Oxygen group received 100% oxygen (2 l/min) via nasal cannula for at least 30 min before delivery. Subjects in the Room Air group were connected to a nasal cannula while on room air. Concentrations of SOD (μg/g of Hb) and GSSG (μM/ml) were measured in maternal and umbilical cord blood. Bivariate and multivariate analyses were used to compare the two groups using the SAS system.

Results

Maternal SOD and GSSG did not differ between the two groups at baseline or after delivery. Concentrations of SOD and GSSG in umbilical cord blood did not differ between groups. More infants in Oxygen Group required delivery room resuscitation (20% vs. 0%, P = 0.03). This difference could not be explained by mode of delivery, infant sex, or other confounders.

Conclusions

Maternal exposure to oxygen during delivery is not associated with changes in umbilical cord SOD or GSSG. Further studies are needed to explore mechanisms responsible for the need of resuscitation in the oxygen group.     

Psychosocial predictors of long-term mortality among women with suspected myocardial ischemia: the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation

This paper evaluated long-term associations between psychosocial factors and premature mortality among women with suspected coronary artery disease (CAD). We tracked total mortality events over a median 9.3 years in a cohort of 517 women [baseline mean age = 58.3 (11.4) years]. Baseline evaluations included coronary angiography, psychosocial testing, and CAD risk factors. Measures included the Spielberger Trait Anxiety Scale, Beck Depression Inventory, self-rated health, and Social Network Index. Cox regression analysis was used to assess relationships. Covariates included age, CAD risk factors, and CAD severity. BDI scores (HR 1.09, 95 % CI 1.02–1.15), STAI scores (HR .86, 95 % CI .78–.93), and very good self-rated health (relative to the poor self-rated health group; HR .33, 95 % CI .12–.96) each independently predicted time to mortality outcomes in the combined model. SNI scores (HR .91, 95 % CI .81–1.06) and other self-rated health categories (i.e., fair, good, and excellent categories) were not significant mortality predictors after adjusting for other psychosocial factors. These results reinforce and extend prior psychosocial research in CAD populations.     

Longitudinal growth of infants in Qatar: Comparison with WHO and CDC growth standards

Longitudinal growth data for infants in Qatar were compared to growth standards published by the CDC and WHO. 300 randomly selected full-term normal infants (150 males, 150 females) in Qatar were followed-up and weight and length were sequentially recorded at 2 months, 4 months, 6 months, 12 months and 18 months age. The mean length for age of girls was higher than those published by the CDC and WHO at 12 and 18 months of age. Using the CDC standard for weight for length detected more wasted infants (9.0% and 6.5%) compared to using WHO standards (6.27% and 6.0%) for males and females, respectively. When WHO and CDC standards are compared, more infants were identified as overweight when the former were used. The WHO standards are preferable because they are based on a leaner breastfed reference and because overweight is likely to be a greater problem in Qatar in the future.     

Age related IGF-I changes and IGF-I generation in thalassemia major

We measured serum concentrations of insulin like growth factor-I (IGF-I) in 20 thalassemic males with short stature (height SDS <-2) and/or slow growth velocity (GV <-1 SD) throughout their childhood and adolescence, compared these data with normal reference data validated in our lab, and evaluated their growth hormone secretion in response to clonidine and glucagon stimulation. We also performed IGF-I generation test on 26 patients with beta thalassemia major (BTM) before and after blood transfusion to evaluate the effect of increased hemoglobin (Hb) on IGF-I and its response to GH. We obtained the following results. 1) No statistical difference in age, HSDS, target height SDS or bone age was observed between BTM patients with growth hormone deficiency (GHD) compared to those with normal GH secretion (GHS). 2) The age-related levels in serum total IGF-I in thalassemic males were significantly decreased from early childhood to 18 years of age compared to normal subjects. Thalassemic males with GHD did not show any significant peak of IGF-I levels until 18 years of age, whereas thalassemic males with normal GH response to provocation (GHS) achieved a significant peak level of IGF-I that was attenuated and late compared to normal males. The basal serum IGF-I concentrations at different ages did not differ between the GHD and GHS groups until the age of 12 years. After 12 years of age, IGF-I levels were significantly higher in thalassemic children with GHS. A significant increase in the circulating basal IGF-I concentrations from 53 +/-35 ug/l to 82.6 +/- 39 ug/L was achieved with increasing Hb concentration after blood transfusion. The serum total IGF-I levels increased significantly with the administration of human growth hormone (hGH) for 4 days, both before and after blood transfusion. The peak IGF-I response to GH injections did not differ before compared to after blood transfusion. The percent increment of IGF-I levels generated after GH injections was higher in thalassemic children with GHD as compared to those with GHS both before and after blood transfusion. In conclusion, our results showed that agerelated serum IGF-I concentrations were significantly lower in short thalassemic patients, with and without GHD, during childhood and adolescence, compared to normal standards. Correction of anemia significantly increased serum concentration of IGF-I but does not affect the increase of IGF-I in response to GH stimulation.     

Association of MTHFR and TYMS gene polymorphisms with the susceptibility to HCC in Egyptian HCV cirrhotic patients

Clinical and Experimental Medicine - Identification of host genetic factors influencing the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV)...