Prognostic value of chromosome 1 and 8 copy number in invasive ductal breast carcinoma among iranian women: An interphase FISH analysis

Breast cancer is amongst the leading causes of death in women worldwide and the most common cancer amongst Iranian women. Unfortunately, the current clinical and histological criteria can only help 60 percent of women with breast cancer in diagnosis and long-term treatment. Therefore, genetic markers both at single gene and chromosomal level can play an important role in improving the diagnosis and prognosis of breast cancer patients. The aim of this retrospective study was to investigate the role of chromosome 1 and 8 copy number assessed by interphase fluorescence in situ hybridization (FISH), as prognostic parameters in 50 Iranian women, aged 35 to 64 years, with sporadic invasive ductal breast carcinoma. Chromosome 1 and 8 copy numbers were evaluated in relation to established clinicopathological parameters, the immunohistochemical markers ER, PR, P53 and cathepsin D, DNA index by flow cytometry, age and survival status of the patients. FISH using centromeric probes for chromosomes 1 and 8 was applied to interphase cell suspensions prepared from archived, Carnoyfixed tumor cells and selected paraffin-embedded tumor sections. Aneusomy for chromosomes 1 and 8 was present in all 50 patients to different levels. The total abnormality rate for chromosome 1 was 33.92 percent (4.24 percent monosomy and 29.68 percent polysomy), whereas for chromosome 8 this rate was 28.30 percent (6.48 percent monosomy and 21.82 percent polysomy). Statistically significant association (p<0.05) was demonstrated between monosomy 1 and patients’ age below 50 years, and between monosomy 1 and poor survival, respectively. Disomy 8 was significantly associated with P53 expression. A borderline significant correlation was demonstrated between polysomy 8 and diploid DNA content, as well as between disomy 1 and disease-free status of the patients. Chromosome 1 and 8 copy numbers may be considered as useful prognostic markers in invasive ductal carcinoma of the breast.     

Attenuation of morphine withdrawal signs by a D1 receptor agonist in the locus coeruleus of rats

In the present study, the effects of intra-locus coeruleus injection of a dopamine D(1) receptor agonist (SKF38393) on naloxone-induced withdrawal signs of morphine-dependent rats were examined. Twenty different withdrawal signs were assessed. The total withdrawal score was calculated and used as an index of withdrawal intensity for comparison. The D(1) agonist and antagonist were injected 15 and 30 min prior to expression of naloxone-induced withdrawal signs, respectively. SKF38393 (2 and 4 microg/site) decreased while SCH23390 (a D(1) antagonist) had no effect on the total withdrawal score. On the other hand, SCH23390 (25 ng/site) reversed the SKF38393 effect. It may be concluded that activation of dopamine D(1) receptors in the locus coeruleus attenuates naloxone-induced withdrawal.     

Fibrocystic changes at anterosuperior femoral neck: prevalence in hips with femoroacetabular impingement

PURPOSE: To retrospectively evaluate if there is an association between juxta-articular fibrocystic changes at the anterosuperior femoral neck and femoroacetabular impingement (FAI). MATERIALS AND METHODS: The institutional review board approved this study and did not require informed patient consent. An orthopedic surgeon and a radiologist in consensus retrospectively reviewed the anteroposterior (AP) pelvic radiographs of 117 hips with FAI and compared these images with the AP radiographs of a control group of 132 hips with developmental dysplasia (DD) to determine the prevalence of juxta-articular fibrocystic changes at the anterosuperior femoral neck. Criteria for juxta-articular fibrocystic changes at the anterosuperior femoral neck were location close to the physis and a diameter (of the fibrocystic change) of greater than 3 mm. The sensitivity and specificity of AP pelvic radiography in the detection of these fibrocystic changes were calculated by using an additional 61 hips with FAI and on the basis of findings at magnetic resonance (MR) arthrography, which was routinely performed for assessment of FAI. In 24 patients who underwent joint-preserving surgery for FAI, the fibrocystic changes were localized intraoperatively and the spatial relation of the region of these changes to the area of FAI was identified. Joint-preserving surgery consisted of anterior surgical dislocation of the hip with osteochondroplasty of the proximal femur and/or the acetabular rim to improve the impingement-free range of hip motion. For statistical comparisons, nonparametric tests were performed. RESULTS: Fibrocystic changes were identified on the AP radiographs of 39 (33%) of the 117 FAI-affected hips and on none of the radiographs of the 132 DD-affected hips. According to MR arthrogram findings, the sensitivity, specificity, and positive and negative predictive values of AP pelvic radiography were 64%, 93%, 91%, and 71%, respectively. The mean diameter of the juxta-articular fibrocystic changes was 5 mm (range, 3-15 mm); smaller lesions were more prevalent. Dynamic MR imaging with the hip flexed and intraoperative observations revealed a close spatial relationship between the region of the fibrocystic changes at the anterosuperior femoral neck and the acetabular rim. CONCLUSION: The high prevalence of juxta-articular fibrocystic changes at the anterosuperior femoral neck and their spatial relation to the impingement site suggest an association and possible causal relationship between these alterations and FAI.     

Assessment of fertility among mustard-exposed residents of Sardasht, Iran: a historical cohort study

BACKGROUND: Mustard gas (HD) is an alkylating agent with mutagenic and carcinogenic effects. Previous reports have demonstrated the ability of this class of compounds to cause adverse reproductive effects, however as of the time of this writing, few correlations have been established between HD exposure and human infertility. In the present study we hypothesize that infertility among mustard-exposed individuals is higher than among the general population. METHODS: 117 couples, 90 with at least one partner, and 27 with both partners exposed to HD in June 1987, were evaluated for occurrence of infertility (defined as the failure to conceive after 12 months of unprotected intercourse). Two groups of subjects were considered in order to establish dose-responsive effect of HD on fertility. One cohort was married at the time of exposure and were evaluated in a time period 12 months from that date. The second cohort married after the date of exposure and each couple was evaluated for a year during a period following marriage. Measurements of these subjects were compared with worldwide incidence of fertility. RESULTS: A 7.5% rate of infertility was observed among couples who were married at the time of exposure; and a rate of 10.3% was noted among individuals single at exposure and subsequently married, for an overall rate of 8.3%, which compares with a worldwide rate of 10-15%. Conclusions: This study showed that within a population of HD-exposed individuals, elevated environmental levels of the agent during a time period in which couples were actively attempting to conceive, failed to correlate with increased risk of infertility. However, these results must be interpreted with caution based on experimental design which limits the definition of infertility to one 12 month time period.     

Comparative performances,under laboratory conditions,of seven pyrethroid insecticides used for impregnation of mosquito nets

OBJECTIVE: To compare the efficacy of seven pyrethroid insecticides for impregnation of mosquito nets, six currently recommended by WHO and one candidate (bifenthrin), under laboratory conditions. METHODS: Tests were conducted using pyrethroid-susceptible and pyrethroid-resistant strains of Anopheles gambiae and Culex quinquefasciatus. Knock-down effect, irritancy and mortality were measured using standard WHO cone tests. Mortality and blood-feeding inhibition were also measured using a baited tunnel device. FINDINGS: For susceptible A. gambiae, alpha-cypermethrin had the fastest knock-down effect. For resistant A. gambiae, the knock- down effect was slightly slower with alpha-cypermethrin and much reduced following exposure to the other insecticides, particularly bifenthrin and permethrin. For susceptible C. quinquefasciatus, the knock-down effect was significantly slower than in A. gambiae, particularly with bifenthrin, and no knock-down effect was observed with any of the pyrethroids against the resistant strain. Bifenthrin was significantly less irritant than the other pyrethroids to susceptible and resistant A. gambiae but there was no clear ranking of pyrethroid irritancy against C. quinquefasciatus. In tunnels, all insecticides were less toxic against C. quinquefasciatus than against A. gambiae for susceptible strains. For resistant strains, mortality was significant with all the pyrethroids with A. gambiae but not with C. quinquefasciatus. Inhibition of blood-feeding was also high for susceptible strains of both species and for resistant A. gambiae but lower for resistant C. quinquefasciatus; bifenthrin had the greatest impact. CONCLUSIONS: Efficacy for impregnation of mosquito nets against A. gambiae was greatest with alpha-cypermethrin. Bifenthrin is likely to have a significant comparative advantage over other pyrethroids in areas with pyrethroid resistance because of its much stronger impact on the nuisance mosquito, C. quinquefasciatus, despite its slower knock-down effect and irritancy. Selection of pyrethroids for mosquito vector control and personal protection should take into account the different effects of these insecticides, the status of pyrethroid resistance in the target area, and the importance of nuisance mosquitoes, such as C. quinquefasciatus.     

Plaque blush,branch location,and calcification are angiographic predictors of progression of mild to moderate coronary stenoses

Background

Angiographic predictors of plaque progression are weak and few: length, irregular surface, turbulence, low shear, and (in some studies) eccentricity and calcification. Having noted plaques that briefly retained dye after angiography, we interpreted these as plaques with a fissured surface or neovascularization and hypothesized that progression would be predicted by “plaque blush.”

Methods

Plaques (<50% diameter stenosis) in 68 pairs of angiograms, 5.6 ± 4.8 months apart, were reviewed by 2 blinded observers. The presence of plaque blush, calcification, clot (mobile defect), eccentricity, and a branch point location were compared between progressing (≥20% stenosis increase) and nonprogressing plaques.

Results

Sixteen lesions in 15 patients progressed from 29% ± 13% to 68% ± 14% over a period of 8.1 ± 7.9 months. Patients with and without progression were similar in sex, age, congestive heart disease risk factors, medications, interval between angiograms, clinical presentation, and initial stenosis severity. By logistic regression, plaque blush (BL) (P = .002), calcification (CA) (P = .024), and a branch (BR) point location (P = .001) predicted plaque progression. The odds ratio for plaque progression (ORp) was calculated as ORp = e^{2.5 × BL + 1.8 × CA + 2.6 × BR}. Using an ORp of 1/3, the model has 81% sensitivity and 77% specificity. A second analysis in which each progressive lesion was compared with proximal and distal lesions and with one in a different coronary artery yielded similar results.

Conclusions

In mild to moderate coronary stenoses, studied retrospectively, plaque blush (a new sign) and a branch point location were strong predictors of plaque progression, whereas calcification was a weak predictor of progression.     

Docosahexaenoic acid prevents resistance to antiepileptic drugs in two animal models of drug-resistant epilepsy

Objectives: One-third of epileptic patients are resistant to antiepileptic drugs. Few clinical studies with small sample size indicate that polyunsaturated fatty acids could control drug-resistant epilepsy. We examined the efficacy of acute and chronic administration of docosahexaenoic acid (DHA) in two animal models of drug-resistant epilepsies, i.e. 6-Hz psychomotor seizures in mice and lamotrigine (LTG)-resistant kindled rats.

Methods: Mice received a single injection of DHA (300?µM, i.c.v.) along with phenytoin (PHT) or LTG (i.p.). Six-Hz electroshock (0.2?milliseconds rectangular pulse width, 3?seconds duration, 44?mA current) was given 15 minutes after DHA, and seizure behaviors were recorded. In LTG-resistant kindled rats, a single dose of DHA (300?µM, i.c.v.) was administered with LTG, and seizure parameters were measured. In chronic treatment, mice received DHA (0.1?g/day, orally) for 30 days. Then, a single dose of LTG or PHT was administered to mice and 6-Hz-induced seizures were recorded. In rats, DHA (1?µM, i.c.v.) was administered during kindling development and effect of LTG in DHA-pretreated LTG-resistant kindled rats was verified.

Results: LTG and PHT did not inhibit 6-Hz seizures in mice after single injection of DHA. However, LTG and PHT inhibited 6-Hz seizures in mice that received DHA for 1?month. Acute or chronic administration of DHA to LTG-resistant kindled rats led to the suppression of kindled seizure parameters by LTG.

Discussion: DHA removes the ‘inherent resistance’ of 6-Hz seizures to PHT and LTG, and prevents the development of pharmacodynamic tolerance to LTG in LTG-resistant kindled rats. DHA might have potential to be used as add-on therapy in patients with refractory epilepsy.     

Thermal injuries in the insensate deep inferior epigastric artery perforator flap: Case series and literature review on mechanisms of injury

With the increasing use of the deep inferior epigastric artery perforator (DIEP) flap, complications that are particularly rare (less than 1%) may start to become clinically relevant. During DIEP flap harvest, cutaneous nerves innervating the flap are necessarily sacrificed, resulting in reduced sensibility. This impaired sensibility prevents adequate thermoregulatory reflexes, like vasodilatation, sweating, and protective behaviors, leaving the reconstructed breast considerably more susceptible to thermal insult. We present four DIEP flap cases who sustained postoperative thermal injury to the reconstructed breast. All four cases were operated on between 2001 and 2008, over the course of 600 DIEP flaps in our unit (an incidence of 0.7%). The injuries occurred between 2 and 18 months after reconstruction. Two patients sustained thermal injury while sunbathing, one while staying in a warm environment, and one sustained the injury while taking a shower. No flap losses ensued, but these were not without morbidity. A literature review discusses other similar cases in the literature and describes the mechanisms for these findings. As a majority of patients will regain both fine‐touch and heat sensation by 3 years postoperatively, it is pertinent that prophylactic measures be instituted during this period, such as the avoidance of sunbathing and the use of cooler shower temperatures for the first 3 years postoperatively. While performing sensory nerve coaptation is the gold standard for maximizing the success of sensory regeneration, this is not always sought and the 0.7% incidence of thermal injury we have encountered suggest the role for greater consideration of such injury. © 2009 Wiley‐Liss, Inc. Microsurgery 2009.