Effect of diet on infant subcutaneous tissue triglyceride fatty acids

Having demonstrated a deficiency in infant cerebral cortex docosahexaenoic acid of formula fed compared with breast milk fed infants, we sought to identify why the extensive subcutaneous tissue triglyceride fatty acid reserves in term new-born infants appeared to be ineffectual in its prevention. In addition to 24 term and six preterm infants who died from 'cot death', tissue was analysed from four perinatal surgical patients and in the former the results were correlated with dietary milk intake. The higher amounts (about 15% by weight) of unsaturated linoleic acid supplied in the formula milks were quantitatively incorporated into the subcutaneous tissue largely at the expense of the saturated palmitic acid possibly compromising adipocyte fluidity. The six preterm infants were in two formula fed groups and there was only one significant difference, namely a higher subcutaneous tissue concentration of alpha-linolenic acid in one of the preterm groups, distinguishing them from their term counterparts. This may imply that the enzymes involved in absorption and digestion of fatty acids are mature in the preterm infant. From birth the mean weight percentage of docosahexaenoic acid (0.4%) fell rapidly to undetectable levels (< 0.05%) in the formula fed group after about two months. It is therefore concluded that if breast feeding is not possible then a minimum daily requirement of 30 mg docosahexaenoic acid (approximately 0.2 g/100 g fatty acids) should be supplied in formulas designed for term infants to prevent the cerebral cortical deficiency of docosahexaenoic acid.     

Localization of a gene for Mobius syndrome to chromosome 3q by linkage analysis in a Dutch family

Mobius syndrome (MIM no. 157900) consists of a congenital paresis or paralysis of the VIIth cranial nerve, frequently accompanied by paralysis of other cranial nerves, orofacial and limb malformations, defects of the musculoskeletal system and mental retardation. Although most patients are sporadic cases, familial recurrence is not rare. Different pedigrees suggest different modes of inheritance. We performed linkage analysis in a large family with autosomal dominantly inherited Mobius syndrome, consisting essentially of asymmetric bilateral facial pareses. After exclusion of the candidate region for Mobius syndrome on 13q12.2-q13, we localized the gene to chromosome 3q21-22, indicating genetic heterogeneity of Mobius syndrome. This heterogeneity is further proven by the exclusion of both loci in a second family with Mobius syndrome.      

Onchocerciasis in the Upper Imo River Basin,Nigeria: Prevalence and Comparative Study of Waist and Shoulder Snips from Mesoendemic Communities

Background

Onchocerciasis is endemic in the Imo River Basin, Nigeria. This study was aimed at assessing the prevalence and intensity of microfilaria of Onchocerca volvulus in the area.

Methods

A cross-sectional study was carried out in the Okigwe Local Government Area, Imo State, Nigeria. Two skin snips (one from the waist and another from the shoulder) were taken from 1024 individuals examined. The survey coverage was high (91.8% of the study population). An individual was considered mf positive if either of the waist or shoulder snips or both were mf positive. The SPSS for Windows package was used for entering and analysis of data.

Results

Thirty-seven percentage of those examined was positive for Onchocerca volvulus microfilariae (39.2% of males and 34.9% of females). The mf prevalence increased steadily with increasing age to reach 70.4% in the oldest age group. The overall mf Geometric Mean Intensity among mf positive individuals was 16 mf/skin snip and was significantly higher among males (18 mf/skin snip) than females (14 mf/skin snip) (p<0.01). A scatter plot of microfilariae numbers in snips from the waist against numbers in snips from the shoulder of the same individuals, showed close correlation (Pearson''s correlation coefficient=+0.90; p<0.01), and those with mf intensities below 10 mf/snip had a more scattering tendency away from the regression line than those with higher mf intensities.

Conclusion

Onchocerciasis is a public health concern in the area. Perhaps, 10 mf/snip is critical intensity threshold for reliable sampling using corneo-scleral punch.     

Genetic analysis of first-trimester miscarriages with a combination of cytogenetic karyotyping, microsatellite genotyping and arrayCGH

Miscarriage is the spontaneous loss of an embryo or fetus before the 20th week of pregnancy. Most miscarriages occur before the end of the first trimester (<13 weeks). Although many risk factors relate to this occurrence, genetic factors play the most important role. Chromosomal abnormalities, including both numerical and structural anomalies, underlie the majority of miscarriages. In this study, we employed a comprehensive approach using cytogenetic karyotyping, polymerase chain reaction (PCR)-based genotyping, and microarray-based comparative genomic hybridization (arrayCGH) in combination to analyze chromosomal profiles of 115 first-trimester miscarriages of Chinese women. Seventy cases (61%) were found to have chromosomal anomalies, of which 90% were numerical and 10% were structural. Cytogenetic karyotyping identified 78.6% (55/70), PCR assays 2.9% (2 triploids), and arrayCGH 18.6% (13/70) of the anomalies. In this study, a microdeletion of 108 kb and four microduplications sizing from 300 to 1460 kb were observed. An advantage of using this combination approach is that microsatellite genotyping and arrayCGH can be accomplished in spite of culture failure and maternal cell contamination. In addition, arrayCGH can detect submicroscopic chromosomal anomalies and gene dosage alterations.     

Detection of KRAS mutations in circulating tumor cells from patients with metastatic colorectal cancer

Background: Quantification of Circulating Tumor Cells (CTCs) as a prognostic marker in metastatic colorectal cancer (mCRC) has already been validated and approved for routine use. However, more than quantification, qualification or characterization of CTCs is gaining importance, since the genetic characterization of CTCs may reflect, in a real time fashion, genetic profile of the disease. Objective: To characterize KRAS mutations (codon 12 and 13) in CTCs from patients with mCRC and to compare with matched primary tumor. Additionally, correlate these mutations with clinical and pathological features of patients. Methods: Blood samples were collected from 26 patients with mCRC from the AC Camargo Cancer Center (São Paulo-Brazil). CTCs were isolated by ISET technology (Isolation by Size of Epithelial Tumors; Rarecells Diagnostics, France) and mutations analyzes were performed by pyrosequencing (QIAGEN). Results: KRAS mutation was detected in 7 of the 21 cases (33%) of samples from CTCs. In matched primary tumors, 9 of the 24 cases (37.5%) were found KRAS mutated. We observed that 5 of the 9 samples with KRAS mutation in their primary tumor had also KRAS mutation in CTCs, meaning a concordance of 71% of matched cases (P = 0.017). KRAS mutation neither on primary tumor nor in CTCs was associated with clinical-pathological parameters analyzed. Conclusion: Faced with a polyclonal disease like colorectal cancer, which is often treated with alternating and successive lines of chemotherapy, real time genetic characterization of CTCs, in a fast and feasible fashion, can provide important information to clinical management of metastatic patients. Although our cohort was limited, it was possible to show a high grade of concordance between primary tumor and CTCs, which suggests that CTCs can be used as surrogate of primary tumors in clinical practice, when the knowledge of mutation profile is necessary and the primary tumor is not available.