Multifocal haemorrhagic brain damage following hypoxia and blood pressure lability: case report and rat model

P. S. Pahlavan, W. Sutton, R. J. Buist and M. R. Del Bigio (2012) Neuropathology and Applied Neurobiology 38 , 723–733 Multifocal haemorrhagic brain damage following hypoxia and blood pressure lability: case report and rat model Aims: Haemorrhagic brain damage is frequently encountered as a complication of premature birth. Much less frequently, multifocal petechial haemorrhage is identified in asphyxiated term newborns. Our goal was to develop an experimental rat model to reproduce this pattern of brain damage. Methods: Neonatal rat pups were exposed to a 24‐h period of 10% or 8% hypoxia followed by a single dose of phenylephrine. Acute and subacute changes, as well as long‐term outcomes, were investigated by histology, brain magnetic resonance imaging and behavioural assessment. Immunostaining for vascular endothelial growth factor and caveolin‐1 was performed in the rat brains as well as in a 17‐day human case. Results: Small foci of haemorrhage were identified in almost all regions of the rat brain subjected to hypoxia plus phenylephrine, but not hypoxia alone. Exposure to 8% hypoxia was associated with more haemorrhagic foci than 10% hypoxia. With rare exceptions, the blood deposits were too small to be detected by magnetic resonance imaging. Altered immunohistochemical detection of vascular endothelial growth factor and caveolin‐1 in the child and the rat model suggests a role for blood–brain barrier compromise. There were no clear behavioural changes and no residual morphological abnormalities in the 78‐day follow‐up of the rats. Conclusions: We conclude that transient hypoxia, in a dose‐dependent manner, can weaken the vasculature and predispose to brain haemorrhage in the situation of labile blood pressure. Persistent hypoxia is likely to be important in the genesis of permanent severe brain damage.     

Distribution of 5,10-methylenetetrahydrofolate reductase (C667T) polymorphism and its association with red blood cell 5-methyltetrahydrofolate in the healthy Iranians

BACKGROUND AND AIMS: Homozygosity for the thermolabile variant of 5,10-methylenetetrahydrofolate reductase (C677T) that causes hyperhomocysteinemia has been reported in 5-15% of general populations. This mutation has also been suggested to be positively associated with the risk of vascular disease and neural tube defects. It has also been suggested that present dietary reference values may need to be altered for people heterozygote or homozygote for this mutation as tissue folate status has been reported to be compromised by these genetic variants. The aims of this study were to investigate the distribution of 5,10-methylenetetrahydrofolate reductase (C677T) polymorphism in a population of Shiraz, south west of Iran and to test the hypothesis that folate status is compromised by this mutation in our population. METHODS: In this study age, body mass index, plasma and red blood cell 5-methytetrahydrofolate, plasma total homocysteine and vitamin B12 of 391 healthy Iranians (198 men and 193 women) together with methylenetetrahydrofolate reductase C667T genotypes were determined. The correlates of methylenetetrahydrofolate reductase polymorphism were determined using univariate and multivariate statistical analysis. RESULTS: The frequencies of CC, CT and TT genotypes were 56.2%, 38.7% and 5.1%, respectively. The C and T allele frequencies were determined to be 0.76 and 0.24, respectively and this polymorphism was compatible with Hardy-Weinberg equilibrium (X2=1.54, df=2, P=0.46). Among all the variables examined, red blood cell 5-methyltetrahydrofolate (P=0.007, ANOVA) and plasma 5-methyltetrahydrofolate (P=0.012, ANOVA) were significantly lower in individuals with TT genotype than those with either CC or CT genotype. Plasma total homocysteine was significantly higher in individuals with TT than those with either CC or CT genotype at below the median levels of red blood cell 5-methylterahydrofolate (P=0.03, ANOVA) and plasma 5-methylterahydrofolate (P=0.04, ANOVA). Univariate (r=-0.16, P=0.002) and multivariate analysis (beta=-0.0005, P=0.003) showed that red blood cell 5-methylterahydrofolate was the strongest correlates of methylenetetrahydrofolate reductase genotypes. CONCLUSIONS: Results from this study suggest that methyltetrahydrofoate reductase C667T genotypes are strongly and independently associated with low red blood cell 5-methylterahydrofolate that has been reported to be a more reliable and long-term marker for body's folate status among Iranians. These results may suggest that substantial minority of people in general populations may have increased folate needs and this may place doubts on the validity of assuming "normality" for nutrient requirements in any general population.     

Efficacy of fine‐needle aspiration biopsy in diagnosis of breast cancer: A retrospective study of 303 cases in Bahrain

Breast cancer is a leading cause of death in many countries worldwide and breast lesions remain a common diagnostic dilemma. Fine‐needle aspiration biopsy (FNAB) has been suggested as the most important, first line, minimally invasive measure in the management of patients with breast lesions. The aim of this study is to evaluate the efficacy of FNAB in patients with breast lesions by comparing the diagnostic accuracy of cytology results with that of the definitive histological examination outcome and also to investigate the added value of a single aspirator experience to the overall diagnostic precision and compared with the internationally published results. A retrospective study of 303 breast FNAB samples were carried out by a single experienced cytopathologist with complete comparison records. The prevalence of positive cytologic diagnosis for the breast cancer was determined to be 20.4%. The overall diagnostic accuracy of FNAB was 97.9%, with a specificity and sensitivity of 98.3 and 96.5%, respectively. The overall positive and negative predictive values were determined to be 93.2 and 99.2%, respectively. In addition, the sensitivity was comparable in cases that have been attempted by palpation‐guided sampling compared with those aspirations that were carried out under US guidance. Results from this study confirm that FNAB biopsies performed and reported by a dedicated, single, skilled cytopathologist are highly effective in diagnosis of breast lesions and reliable in differentiating benign and malignant breast lesions with an overall high efficacy in a specialized laboratory‐based FNAB clinic. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Artificial tactile sensing approach in aortic-repair-laparoscopy: aorta cross clamping during surgery

Abdominal aortic aneurysm is one of the most common diseases of the vascular system for which the most definitive treatment is surgery. Laparoscopy is a primary method of minimally invasive surgery that could be useful in aortic repair surgeries. Although this method of surgery has significant advantages, the difficulty of exactly distinguishing the aorta from its surrounding tissues is its main drawback; this can cause many problems during the aorta cross clamping process. One of the most important limitations is that it is a time-consuming process; aorta cross clamping leads to increases in surgery duration. Artificial tactile sensing is an innovative technology aiming to make tactile data more available for surgeons, especially in situations where developments in technology make the surgeons less efficient. In this paper, considering the present problems during aortic repair laparoscopy, applicability of a novel tactile robotic system capable of cross clamping an artery during laparoscopy was evaluated. Having considered a small, 5-degree-of-planar-freedom robot and imitated surgeon's palpation using software, the path followed by the tip of the new tactile robotic system was extracted. It is shown that this new tactile robotic system is well capable of dissecting an artery from its adjacent tissues in a short time with an acceptable accuracy. The functional principles of the tactile robotic system capable of cross clamping the aorta during laparoscopy will also be presented.     

Association of red blood cell 5-methyltetrahydrfoate folate with bone mineral density in postmenopausal Iranian women

Recent studies have suggested that hyperhomocystenemia and low plasma folate are associated with fracture and also bone mineral density (BMD) and that they may contribute to the pathogenicity of osteoporosis in postmenopausal women. However, as plasma total homocysteine (tHcy) and plasma folate can be regarded as short-term markers when compared to a long-term variable such as BMD, in this study we tested the hypothesis that low red blood cell 5-methyltetrahydrofolate (RBC 5-MTHFR) as a long-term marker of the folate status may be a better predictor of BMD than plasma 5-MTHF, and its deficiency may contribute to the pathogenecity of osteoporosis in postmenopausal Iranian women. The BMD at the femoral neck and lumbar spine (measured by dual-energy X-ray absorptiometry, DXA) together with anthropometric and biochemical components of the homocysteine re-methylation pathway including plasma tHcy, 5-MTHF and vitamin B12, RBC 5-MTHF and creatinine were determined in 366 postmenopausal women. RBC 5-MTHF was more highly correlated with BMD at the lumbar spine ( r =0.21, P =0.001) and femoral neck ( r =0.19, P =0.004) than was plasma 5-MTHF (lumbar spine; r =0.14, P =0.03 and femoral neck; r =0.17, P =0.006). Stepwise multiple linear regression analyses revealed that RBC 5-MTHF was one of the predictors of BMD explaining 4.3 and 4.0% variance of BMD at the lumbar spine and femoral neck, respectively, whereas plasma 5-MTHF was excluded in the model and not determined to be a predictor of BMD at both the lumbar spine and femoral neck when adjusted for age, BMI, years since menopause and RBC 5-MTHF. This study suggests that RBC 5-MTHF is a better predictor of BMD than plasma 5-MTHFR when compared to a long-term marker such as BMD, and its deficiency is associated with low BMD that may contribute to the pathogenecity of osteoporosis in postmenopausal women.     

Parathyroid carcinoma: A rare case with mandibular brown tumor

Parathyroid carcinoma constitutes less than 1 % of primary hyperparathyroidism. The male to female ratio is approximately equal and the mean age at presentation is 40 years. In about half of the patients there is a palpable cervical mass, and serum calcium level is usually above 14 mg/dl. In a case report we present a 21-year-old man with a non-tender, non-mobile bulging mandibular mass. He suffered from fatigue, recent weight loss, hoarseness, polydipsia, polyuria, hematuria, recurrent renal stones and bouts of constipation and diarrhea. A mandibular biopsy confirmed brown tumor. Serum calcium level was 15.4 mg/dl. Cervical ultrasound revealed a hypoecho area suspicious of parathyroid adenoma. Parathyroid carcinoma was later confirmed and en bloc resection was performed. During a two-year follow up there has been no evidence of recurrence or hypercalcemia. This unique case of parathyroid carcinoma in conjunction with brown tumor is the second reported case worldwide.