An intron variant in the FLT1 gene increases the risk of preeclampsia in Iranian women

ABSTRACT

Background: Preeclampsia is a hypertensive disorder that affects pregnancy, mother, and fetus. Pathogenesis of preeclampsia could be associated with the angiogenesis pathways. The vascular endothelial growth factor (VEGF) family is one of the important factors for normal pregnancy and angiogenesis. Genetic variations in the gene family members may play a role in the etiology of preeclampsia. We investigated the possible association between VEGFA gene rs3025039, and VEGFR1 (FLT1) gene rs722503 polymorphisms and preeclampsia in a sample of Iranian patients. Methods: Genotyping was performed in 395 women, including, 204 pre-eclamptic pregnant women and 191 healthy normotensive pregnant women by using the PCR-RFLP method. Results: The rs722503 polymorphism was associated with preeclampsia under the dominant model (P = 0.04, OR = 1.53, 95% CI: 1.03–2.27). No significant difference was observed for the rs3025039 alleles and genotypes in the studied groups. Conclusions: Based on our study, rs722503 polymorphism in the FLT1 gene may play an important role in susceptibility to preeclampsia.     

Oestrogen receptors are prognostic factors in malignant peritoneal mesothelioma

Background

Malignant peritoneal mesothelioma (MPM) is a rare and fatal cancer. Females are found to survive longer than males after treatment, suggesting a possible involvement of hormonal factors. Estradiol is involved in cellular proliferation of a number of cancers and acts mainly through oestrogen receptors (ERs). Hence, we examined the expression of oestrogen receptors with correlation to prognosis.

Methods

Oestrogen receptors expression was examined using immunohistochemistry on 42 paraffin-embedded sections of MPM tumours. Kaplan–Meier survival curves were analysed to determine the significance of ER expression in relation to prognosis.

Results

ER-β (nuclear) was detected in 33 (79 %) patients. ER-β was also detected in the cellular cytoplasm of 9 (21 %) patients. Presence of ER-β (nuclear) was associated with favourable survival (univariate analysis, P = 0.001), whereas the presence of ER-β (cytoplasm) was associated with a poor survival (P = 0.014). Multivariate Cox regression analysis revealed the absence of ER-β (nuclear) and the presence of ER-β (cytoplasm) to be independent predictive factors for poor disease outcome (hazard ratio 5.4, 95 % confidence interval 1.86–15.75; P = 0.002 and hazard ratio 8.0, 95 % confidence interval 1.8–34; P = 0.005), respectively. ER-α (nuclear) was detected in only 4 (9 %) of patients and not statistically significant (univariate analysis, P = 0.066).

Conclusion

The presence of ER-β (cytoplasm) is associated with poor prognosis. The favourable survival association observed in patients with ER-β (nuclear) raises a question about the molecular mechanisms of the tumorigenic roles of ER-β in each cellular compartment and requires further studies.     

An unusual endoscopic presentation of solitary rectal ulcer syndrome

Solitary rectal ulcer syndrome (SRUS) is an uncommon rectal disorder. Massive rectal bleeding is a rare presentation of SRUS, and can pose an endoscopic challenge in differentiating from other causes of massive rectal bleeding. A 22-year-old man presented with massive rectal bleeding which had SRUS with spurting bleeding on lower endoscopic evaluation. He was treated by endoscopic hemostasis using argon plasma coagulation. He had no complaint after a month and follow up lower endoscopy proved complete healing within two months. SRUS should be considered as a potential cause of massive rectal bleeding.     

Further studies on anti-inflammatory activity of maprotiline in carrageenan-induced paw edema in rat

Antidepressant drugs are commonly used for treatment of different medical disorders besides of psychiatric diseases. Accumulating evidence suggests that antidepressants exhibit anti-inflammatory activity in vivo and in vitro conditions, but the mechanisms of this property are not clear very well. In our earlier work, we demonstrated that i.c.v. and i.p. injection of maprotiline, as an antidepressant, decreased paw edema at the fourth hour after subplantar injection of carrageenan. Therefore, this work was undertaken to investigate anti-inflammatory effects of maprotiline in more details. Our results verified that i.p. (25 and 50 mg/kg) and i.c.v. (100 μg/rat) application of maprotiline significantly reduced paw edema at 1, 2, 3 and 4 h intervals after carrageenan challenge. Pathological examinations and MPO activity also showed that both i.p. and i.c.v. maprotiline considerably inhibited infiltration of PMN leucocytes into the inflamed paws. Additionally, i.p. and i.c.v. maprotiline at all applied doses noticeably declined levels of IL-1β into the site of inflammation, while only i.p. maprotiline at a dose of 50 mg/kg significantly decreased TNF-α levels in the carrageenan-injected paws.These results confirmed anti-edematogenic activity of i.p. and i.c.v. maprotiline in the carrageenan induced paw edema model and showed that these properties of maprotiline might be mediated through inhibition of PMN infiltration and release of IL-1β and TNF-α.     

Experience with the prefabricated free fibula flap for reconstruction of maxillary and mandibular defects.

PURPOSE: We report our 11-year experience with a new technique to prefabricate the osteocutaneous free fibula flap to reconstruct defects of the maxilla and mandible not amenable to conventional methods of treatment. MATERIAL AND METHODS: We treated 11 patients aged 17 to 47 years with jaw defects using prefabricated free fibula grafts from 1994 to 2005. We prepared the fibula on the leg with a 6- to 8-mm muscle cuff; next we transferred the bone flap to the surface of the leg without severing the pedicle, and then covered the muscle almost circumferentially by partial thickness skin graft. The bone flap was left in place with its pedicle intact for 2 to 3 months, after which the skin graft had taken and the flap was free of inflammation. The fibula flap was then transferred to the face, fixed in place with plates, and microvascular anastomosis was performed. Implant placement was completed 4 to 6 months after transfer of the flap to the oral cavity. RESULTS: Graft take was unremarkable in all cases. There were no cases of infection and only minor complications. Edema of the flap may be encountered, which subsides with time. If the mandible is not edentulous the mandibular teeth may bite into the flap, but these wounds heal by the time the patient is ready for implant insertion (3 to 6 months). Implants placed in the fibula were successful during the follow-up period (2 to 13 years). CONCLUSION: The prefabricated fibula with a "banking time" on the leg for flap maturation seems to be a better choice compared with other methods of using the fibula for reconstruction and has passed the test of time. We hereby report this new technique to add to the armamentarium of jaw reconstruction surgery.     

Relation of beta(2)-adrenoceptor haplotype to risk of death and heart transplantation in patients with heart failure

Heart failure (HF) is characterized by neurohormonal activation of the sympathetic nervous and renin-angiotensin systems. Genetic polymorphisms in these systems could alter the prognosis in HF. We hypothesized the genetic polymorphisms in the sympathetic nervous and renin-angiotensin systems are associated with adverse outcomes, defined as death or heart transplantation in patients with HF. A total of 227 patients with HF were enrolled from a tertiary care clinic and followed for outcomes for < or =4 years. Eight polymorphisms in 6 genes were genotyped: beta(1)-adrenergic receptor (ADRB1, S49G, R389G), beta(2)-adrenergic receptor (ADRB2, G16R, Q27E), alpha(2c)-adrenergic receptor (ADRA2C, insertion/deletion 322-325), angiotensinogen (AGT, M235T), angiotensin receptor type 1 (AGTR1, 1166A>C), and angiotensin-converting enzyme (ACE, insertion/deletion in intron 16). Most patients were treated according to consensus guidelines. Male gender (hazard ratio 2.24, 95% confidence interval 1.27 to 3.94), higher New York Heart Association functional class (hazard ratio 2.54, 95% confidence interval 1.84 to 3.52), and 2 copies of ADRB2 Arg16Gln27 haplotype (hazard ratio 1.91, 95% confidence interval 1.09 to 3.36) increased the risk of adverse outcomes. In contrast, a higher serum sodium level (hazard ratio 0.91, 95% confidence interval 0.86 to 0.97) and higher creatinine clearance (hazard ratio 0.99, 95% confidence interval 0.98 to 0.99) decreased the risk of adverse outcomes. None of the other genotypes/haplotypes were associated with adverse outcomes. In conclusion, ADRB2 Arg16Gln27 haplotype may significantly increase the risk of adverse outcomes in patients with HF receiving contemporary HF pharmacotherapy.     

Dyadic support and quality-of-life after radical prostatectomy

Background

Treatment side effects after radical prostatectomy include urinary, sexual, and bowel dysfunction. These functional declines, coupled with the bother associated with these dysfunctions, lead to a complicated pattern of change in quality-of-life and decreased self-efficacy.

Methods

In this study, 72 men who underwent radical prostatectomy 6-weeks prior were randomly assigned to usual health care control group or peer-to-peer support (dyadic support) group. The dyadic meetings were held once a week for 8 weeks. Measured pre- and post-test was general health-related quality-of-life (SF-36), prostate cancer-specific quality-of-life (UCLA Prostate Cancer Index), and self-efficacy (Stanford Inventory of Cancer Patient Adjustment).

Results

By 8 weeks, self-efficacy significantly improved for men in the experimental group, but not for men in the control group. A series of logistic regression analyses showed that the dyadic intervention significantly accounted for changes in physical role functioning, bowel function, mental health, and social function. Age, education, and self-efficacy had significant interaction effects and increased the effects of the dyadic intervention on several outcomes.

Conclusions

The intervention had a significant impact on how men react socially and emotionally to the side effects of radical prostatectomy.     

Complete Surgical Repair of Tetralogy of Fallot in Adults,Is It Ever Too Late?

A minority of patients with Tetralogy of Fallot (TF) survive into adulthood. These patients have been subjected to a prolong period of cyanosis and hypoxia. The aim of this study is to assess the benefits of total correction of TF in this adult population. From August 1995 to March 2005, fifty one patients underwent total correction of TF. The mean age was 22.2 years (range 16 to 38 years). There were 31 males and 20 females. Twenty two percent of patients were in NYHA functional class III prior to the operation. The mean gradient across the right ventricular outflow tract was 81.7 mmHg (range 30 to 130 mmHg). The operation was performed through the right ventricle in the majority of patients. Transannular patch was used in 33 patients. The mean follow-up period was 42 months ranging from 1 to 116 months. Hospital mortality was 1.9% (1 patient), and one patient died three months after the operation. Post-operatively 87.3% of patients were in NYHA functional class I. During the follow-up period four patients required re-operation; two for residual ventricular septal defect, one for residual pulmonary stenosis and one had pulmonary valve replacement for severe pulmonary regurgitation. Complete repair of TF in adults is feasible with acceptable mortality and morbidity. The main benefit of the operation is functional improvement in this patient population.