Epidemiological aspects of cleft lip and palate in Iran

Orofacial clefts, including cleft lip with or without cleft palate (CL (P)), are common congenital malformations, second only to clubfoot in frequency of occurrence. The epidemiology and genetics of this disorder have been studied extensively in various countries by several investigators. The objective of this study is to assess the epidemiology and some genetic aspects of orofacial clefting at Imam Khomeini Hospital in Tehran. This study was a 7-year case series (retrospective) study from 1999 to 2006. The setting for the study was Imam Khomeini Hospital in Tehran, and the participants were all consecutive surgical cases with orofacial clefts referred to this hospital. One hundred and 77 cases of cleft lip and/or cleft palate were recorded during these 7 years. Seventy four of them (41.8%) were female and 103(58.2%) were male (M/F Ratio=1.39). Of all patients, 40 persons (22.6%) had isolated CP, 45 (25.4%) had cleft lip without cleft palate, and 92 (52%) had cleft lip with cleft palate (CL+P). Their M/F ratios were 1.66, 0.6 and 1.96 respectively. Of all CL (P) probands, 41 patients (29.9%) were bilaterally affected. In unilateral cases, the left side was affected nearly twice as frequently as the right side. Among the patients, 23 cases (13%) had other malformations; most commonly head and face abnormalities and then congenital heart disease. Fifty-four patients (30.5%) had consanguine parents; 33 (18.6%) were first cousins, 7 (4%) were second cousins, and 14 (7.9%) were distant relatives. There was a positive family history for cleft syndrome in 23 cases; most commonly CL-P. Our study reveals that the epidemiologic aspects of oral clefts in Iran are very similar to other Caucasian populations. It also suggests that a routine screening such as echocardiography and ruling out skeletal, hearing and visual problems may be necessary in cleft patients especially in children. It seems that genetic counseling and karyotyping can be very useful in patients with multiple malformations.     

Fatty acid–binding protein-2 genotype influences lipid and lipoprotein response to eicosapentaenoic acid supplementation in hypertriglyceridemic subjects

ObjectiveThe blood lipid-lowering effects of eicosapentaenoic acid (EPA) on hypertriglyceridemic subjects with different fatty acid–binding protein-2 (FABP2) genotypes have not, to our knowledge, been previously studied.MethodsTwenty-three FABP2 Ala54 and 23 Thr54 carriers with hypertriglyceridemia (triacylglycerol level >200 mg/dL) were enrolled in this study. Participants took 2 g of pure EPA daily for 8 wk. Fasting blood lipid and lipoprotein profiles were determined and changes from baseline were measured.ResultsBlood lipids and lipoprotein responses of the FABP2 genotypes differed after EPA supplementation. Changes from baseline for triacylglycerol (19.2% decrease for Ala54 and 60.5% for Thr54, P < 0.001), very low-density lipoprotein (20.0% decrease for Ala54 and 60.5% for Thr54, P < 0.001), apolipoprotein CIII (22.8% decrease for Ala54 and 36.4% for Thr54, P < 0.01), and high-density lipoprotein cholesterol (17.6% increase for Ala54 and 30.7% for Thr54, P < 0.01) differed significantly between the two carrier groups. However, changes in total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B were not significant. EPA supplementation increased plasma EPA in Ala54 and Thr54 carriers. Although EPA supplementation increased the level of plasma EPA in both carrier groups, this effect was more pronounced in the Thr54 carriers.ConclusionTherefore, EPA consumption has more favorable effects on blood lipids of hypertriglyceridemics with Thr54 genotype rather than those with Ala54. The level of plasma EPA increases after EPA supplementation. Because the FABP2 Thr54 polymorphism appears to be prevalent in hypertriglyceridemic subjects, increasing EPA intake in these subjects could be an effective strategy for reducing blood triacylglycerol concentration.     

Percutaneous balloon aortic valvuloplasty: a new look at an old procedure: a case report

There has been little change in the technical approach to balloon aortic valvuloplasty (BAV) over the last two decades. Large-caliber sheaths and extra-stiff wires have been used routinely to accommodate the large balloons used for this purpose. Consequently the morbidity (and possibly mortality) rates have been high. With the recent advances in the interventional hardware, a new look at the current approach to BAV is justified. In this report we describe an 89-year-old woman with critical aortic stenosis who underwent rapid and successful BAV by the use of a single 8-French arterial sheath, a regular (and not stiff) wire, and one peripheral balloon. We conclude that BAV can be done easily and safely with the technique and equipment described in this case report.     

Toxicopathological Changes Induced By Combined Exposure To Noise and Toluene in New Zealand White Rabbits

Noise and toluene can have significant adverse effects on different systems in the human body, but little is known about their combination. The aim of this study was to see how their combined action reflects on serum levels of inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β), body weight, and pathological changes in the heart, lung, stomach, and spleen tissues. To do that we exposed New Zealand rabbits to 1000 mg/L toluene and 100 dB of white noise in a chamber specifically designed for the purpose over two consecutive weeks. Serum levels of TNF-α and IL-1β were measured with the enzyme-linked immunosorbent assay (ELISA), whereas Bax and Bcl-2 expressions in tissues were determined with real-time polymerase chain reaction (PCR). Noise and toluene changed TNF-α and IL-1β serum levels on different days following the end of exposure and significantly increased the Bax/Bcl-2 ratio in the lung and spleen. In addition, they induced different pathological changes in the heart, lung, spleen, and stomach tissues. This study has confirmed that exposure to noise and toluene can induce a range of toxicopathological changes, probably by inducing inflammatory pathways and apoptosis, but their combined effects look weaker than those of its components, although histopathological findings suggest the opposite.Key words: body weight, environmental exposure, heart, IL-1β, industrial toxicology, apoptosis, lung, spleen, stomach, TNF-α     

Mutation analysis of BRCA1 and BRCA2 genes in Iranian high risk breast cancer families

Purpose: Germline mutations in either BRCA1 or BRCA2 genes are responsible for the majority of hereditary breast and ovarian cancers. At present, over thousand distinct BRCA1 and BRCA2 mutations have been identified. Specific mutations are found to be common within particular populations, resulting from genetic founder effects. To investigate the contribution of germline mutations in these two genes to inherited breast cancer in Iran, we performed BRCA1/BRCA2 mutation analyses in ten Iranian high risk breast cancer families. This is the first study analysing the complete coding sequences of both genes that concerns the Iranian population. Methods: BRCA1/BRCA2 mutation detection included sequencing of the coding and the 3 and 5 untranslated regions. To detect large genomic rearrangements in the BRCA1 gene semi-quantitative multiplex PCR was performed. Results: Two pathogenic mutations in the BRCA2 gene were detected: a novel deletion c.4415_4418delAGAA and a previously described insertion c.6033_6034insGT. In addition, one intronic variation g.5075–53C>T and a deletion/insertion g.*381_389del9ins29 in the 3 untranslated region of BRCA1 were found in two of the investigated families. Both sequence alterations were absent in an age matched Iranian control group. The BRCA2 homozygous variation p.N372H, previously associated with an increased risk for developing breast cancer, was not identified in this study. We did not detect large genomic rearrangements in BRCA1 in patients tested negatively for disease causing mutations in both genes by standard sequencing. Conclusions: At present, the BRCA2 mutations c.4415_4418delAGAA and c.6033_6034insGT have not been identified in any investigated population except the Iranian. Whether both mutations are specific for the Iranian population or a special subgroup remains to be investigated in larger studies. The absence of BRCA1 mutations in the analysed families may suggest that penetrance or prevalence of BRCA1 mutations may be lower in Iran.     

Qualitative and quantitative promoter hypermethylation patterns of the P16, TSHR,RASSF1A and RARβ2 genes in papillary thyroid carcinoma

The aim of this study was to evaluate the frequency (as qualitative analysis) and level (as quantitative analysis) of promoter hypermethylation of four genes, P16, TSHR, RASSF1A and RARβ2, and to assess their diagnostic or prognostic values in papillary thyroid tumors. Fifty formalin-fixed paraffin-embedded (FFPE) samples consisting of 25 malignant tumors and 25 non-malignant thyroid tumors were analyzed using COBRA method. Promoter hypermethylation of P16, TESH, RASSF1A and RARB2 genes was noted not only in 10, 7, 19 and 13 cases of malignant tumors, but also it was detected in 7, 11, 23 and 8 cases of benign tumors, respectively, limiting its diagnostic usefulness. The quantitative hypermethylation level was significantly higher in malignant tumors compared to benign tumors for P16 (P < 0.004), TSHR (P < 0.006) and RASSF1A (P < 0.001), but the methylation level of RARβ2 (P < 0.31) showed considerable overlap between the two groups. The mean levels of hypermethylation of P16, TSHR and RASSF1A genes were significantly higher in malignant papillary thyroid tumors compared to benign tumors and by choosing the appropriate cutoff for each gene, we could distinguish 9, 9 and 8 PTCs from 25 cases by P16, RASSF1A and TSHR methylation analysis, respectively. According to our results, these three genes, in combination, may be useful as molecular markers. The findings of present study imply that the P16, TSHR and RASSF1A gene promoter hypermethylation may play important roles in the pathogenesis of PTC and can be a potential biomarker for selecting patients with PTC.     

Percutaneous therapy of acute on chronic lower extremity venous occlusive disease

Venous thromboembolic disease is an underdiagnosed disease spectrum with a high mortality and morbidity. Despite significant advances in cardiovascular interventions, venous occlusive disease has not received the attention it deserves from the interventional cardiology community. We describe an 82‐year‐old man with massive left lower extremity DVT who underwent successful percutaneous endovenous intervention (PEVI) with rapid resolution of symptoms. We like to use this case as a call to action and raise awareness of the importance of PEVI in the treatment of extensive venous occlusive disease. © 2009 Wiley‐Liss, Inc.     

The effect of modifiable potentials on hypermethylation status of retinoic acid receptor-beta2 and estrogen receptor-alpha genes in primary breast cancer

Epigenetic silencing of retinoic acid receptor-beta2 (RARbeta2) and estrogen receptor-alpha (ERalpha) expressions have been revealed to be important in the development of approaches for diagnosis and therapy of breast cancer. We aimed to explore the correlation of some potential factors with the hypermethylation status of RARbeta2 and ERalpha genes among Iranian breast cancer patients. The hypermethylation status was investigated in 137 dissected tissues from primary breast cancer patients through methylation-specific PCR. Overall, the methylation frequencies of RARbeta2 and ERalpha genes were observed in 36.5 and 51.1% of participants, respectively. The hypermethylated RARbeta2 was associated with younger age at diagnosis and negative family history of breast cancer. The hypermethylation of ERalpha was correlated positively with smoking, duration of estradiol exposure, ER-negativity in tumors and body mass index (at 5 years ago). The plasma levels of folate and vitamin B₁₂ were inversely related to the hypermethylation status of ERalpha, after controlling for covariates. The risk of ERalpha hypermethylation was increased with high plasma level of total homocysteine. In conclusion, our data provide new insights into the possible effect of some lifestyle-related factors on the aberrant methylation drift of ERalpha and RARbeta2 genes in breast cancer.