Cerebral Palsy

Diabetic foot disease and ulceration is a major complication that may lead to the amputation of the lower limbs. Microangiopathy may play a significant role in the pathogenesis of tissue breakdown in the diabetic foot. However, the precise mechanisms of this process remain unclear and poorly understood. Microvasculature in the skin is comprised of nutritive capillaries and thermoregulatory arteriovenous shunt flow. It is regulated through the complex interaction of neurogenic and neurovascular control. The interplay among endothelial dysfunction, impaired nerve axon reflex activities, and microvascular regulation in the diabetic patient results in the poor healing of wounds. Skin microvasculature undergoes both morphologic changes as well as functional deficits when parts of the body come under stress or injury. Two important theories that have been put forward to explain the abnormalities that have been observed are the haemodynamic hypothesis and capillary steal syndrome. With advances in medical technology, microvasculature can now be measured quantitatively. This article reviews the development of microvascular dysfunction in the diabetic foot and discusses how it may relate to the pathogenesis of diabetic foot problems and ulceration. Common methods for measuring skin microcirculation are also discussed. Copyright (c) 2009 John Wiley & Sons, Ltd.

The importance of microglial cells in the maintenance of a well-functioning central nervous system (CNS) cannot be overstated. As descendants of the myelomonocytic lineage they are industrious housekeepers and watchful sentries that safeguard a homeostatic environment through a number of mechanisms designed to provide protection of fastidious neurons at all times. Microglia become particularly active after homeostasis has been perturbed by physical injury or other insults and they enter into a state of activation which is determined largely by the nature and severity of the lesion. Microglial activation is the main cellular event in acute neuroinflammation and essential for wound healing in the CNS. Recent studies from this laboratory have been focused on microglia in the aging brain and identified structural abnormalities, termed microglial dystrophy, that are consistent with cell senescence and progress to a form of accidental cell death that is marked by cytoplasmic degeneration and has been termed cytorrhexis. Cytorrhexis of microglia is infrequent in the normally aged human brain and non-detectable in aged rodents, but its occurrence increases dramatically during neurodegenerative conditions, including Alzheimer’s disease (AD) in humans and motoneuron disease in transgenic rats. The identification of degenerating microglia has given rise to a novel theory of AD pathogenesis, the microglial dysfunction hypothesis, which views the loss of microglial neuroprotection as a central event in neurodegenerative disease development.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder whose etiology is not understood. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse model is widely used for studying PD. The present study was undertaken to investigate the effect of hydroxysafflor yellow A (HSYA) on MPTP-induced neurotoxicity in mice. Pretreatment with HSYA at a dose of 2, 8 mg/kg for a week was followed by intraperitoneal injection with MPTP (30 mg/kg) for five consecutive days. Next, the subsequent behavior, biochemical index and immunohistochemical manifestations in mice were determined. Behavioral testing showed that MPTP-treated mice exhibited motor deficits but HSYA at dose of 8 mg/kg prevented the appearance of motor abnormalities. Treatment with HSYA at dose of 8 mg/kg attenuated the reduction of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in striatum. It also showed that the activity of SOD, catalase activity and GSH levels were significantly higher, while the levels of malondialdehyde (MDA) and hydroxyl radicals was lower, in the HSYA-treated mice compared to the MPTP-treated mice. The MPTP-treated mice exhibited the loss of tyrosine hydroxylase-containing dopaminergic neurons in substantia nigra. However, HSYA-treated mice showed a protective effect. Our results indicated that HSYA possesses neuroprotective effects and is a promising anti-Parkinson’s disease drug which is worthy of further study.

PURPOSE: Open surgical biopsies of the primary tumor and bone marrow sampling in metastatic disease are the major sources of tumor material for genetic studies in neuroblastoma. The possibility of using cultures of material procured through Fine Needle Aspiration (FNA) for upfront cytogenetic studies of neuroblastomas is studied. METHODS: From January 2006 to April 2008, 18 patients were diagnosed as neuroblastoma on fine needle aspiration cytology (FNAC). FNA material was cultured and processed to obtain metaphases and chromosomal analysis was performed. Minimum of five selected metaphases were analyzed and changes were documented. RESULTS: The diagnosis of neuroblastoma was confirmed by FNAC in all. Among the 18 cases, 9 cases (50%) showed metaphases on cultures. Four cultures did not grow and five cultures got contaminated. Out of the nine cases that showed metaphases, four cases showed cytogenetic abnormalities. Near triploidy and Double minutes (Dmins) were seen in one case and tetraploidy in another case. 1q gain and 2q gain were observed respectively in third and fourth cases. CONCLUSION: FNA provides viable single cell suspension suitable for cultures. This may be a good alternative strategy to acquire material for cytogenetic studies in neuroblastoma.

BACKGROUND: A tethered cord (TC) has been reported in as much as 50% of the patients affected by anorectal malformation (ARM). No guidelines for timing and modality of diagnosis and treatment have been established. We present the preliminary results of a multidisciplinary protocol carried out at our center. METHODS: Seventy-four ARM patients underwent spinal magnetic resonance imaging (MRI). All TC patients underwent videourodynamic (UD), somatosensory-evoked potentials (SEPs), and neurological examination at baseline and, if normal, at 5 and 10 years of age. Conversely, when UD or SEP abnormalities were detected the follow-up was individually tailored at shorter time. RESULTS: 25/74 patients had a neuroradiological TC (33.7%). Based on the results of UD, SEP, and neurological status, four patients were untethered, eight are possible candidates, nine are stable, and four were excluded because of incomplete data. DISCUSSION: Tethered cord is frequent in ARM patients. Because neurological deficits secondary to TC can contribute to neurological disability, we recommend routine MRI examination and a multidisciplinary program of follow-up in cases of TC. Preliminary results suggest the combined use of SEPs and UD could represent a useful adjunct to clinical examination in patients in whom a “wait and see” approach is preferred to the prophylactic surgery.

More than 750 million people are at risk of infection with foodborne liver flukes. Opisthorchis viverrini is considered among the most important of these parasites, due to its strong association with cholangiocarcinoma (CCA). O. viverrini infection results in a chronic inflammatory challenge to the host, which can lead to advanced, pathogen-specific disease sequelae including obstructive jaundice, hepatomegaly, cholecystitis, as well as CCA. However, before disease sequelae are apparent, important inflammatory changes to the liver can be detected early during O. viverrini infection. In a case-control study involving 328 men and women with O. viverrini infection, we determined the presence of advanced periductal fibrosis in asymptomatic, O. viverrini-infected individuals and then measured cytokine responses to O. viverrini excretory/secretory products (ES). In the 200 participants with advanced periductal fibrosis (cases), levels of interleukin-6 (IL-6) to O. viverrini ES were 8 times higher than levels of the 128 O. viverrini-infected individuals without advanced periductal fibrosis (controls). Moreover, elevated IL-6 to parasite ES was associated with increased risk of advanced periductal fibrosis by 63% in a model adjusted for sex and age. The risk of advanced periductal fibrosis was also found to increase with higher levels of IL-6: individuals in the third quartile of IL-6-ES production had a 127% higher risk of developing advanced periductal fibrosis than individuals in the first quartile of IL-6 production. O. viverrini-infected individuals with advanced periductal fibrosis showed other hepatobiliary abnormalities, including reduced gallbladder contractility and the presence of gallbladder sludge. Conclusion: These data strongly implicate a role for parasite-specific IL-6 in the pathogenesis of advanced periductal fibrosis in opisthorchiasis, with possible links to other hepatobiliary abnormalities, including CCA. (HEPATOLOGY 2009.).

Valcamonica is an Italian valley where ferro-manganese industries have been active for a century and where an increased prevalence of parkinsonism was observed. A group of 93 patients (65 from Valcamonica, 28 from the reference area of Brescia city) and 76 controls (52 from Valcamonica, 24 from Brescia) were screened for serum Cu, Zn, Fe, Mn in blood (MnB) and urine (MnU), transferrin, peroxides, alanine (ALT) and aspartate (AST) transaminases and direct bilirubin. Test results were compared among groups according to the residential area and related to the disease severity. Valcamonica patients had a serum-increase of Cu, as well as of AST/ALT ratio, and a serum-decrease of Zn and Fe compared with other subgroups of cases and controls. Cases and controls from Valcamonica had higher MnB and MnU levels compared to cases and controls from Brescia. After controlling for the duration of illness, the Unified Parkinson’s Disease Rating Scale III domain correlated with serum Cu and AST/ALT ratio. Our results suggest the possibility that, in this area, a lifetime exposure to neurotoxicants and to Mn in particular, when accompanied to a subclinical liver dysfunction, may pose an increased risk for neurodegenerative disorders via metal metabolism (Cu, Zn, Fe) abnormalities.

Although myocardial perfusion imaging (MPI) with pharmacologic stress is the standard method for screening coronary artery disease (CAD) in patients with left bundle branch block (LBBB), controversies remain about its correct interpretation. We sought the best interpretation approach in these patients to achieve higher accuracy. Forty-two patients with LBBB underwent MPI with dipyridamole stress and the criteria for positive results with four patterns of interpretation were as follows: Pattern A: any reversible or irreversible perfusion abnormality in the myocardium irrespective of the location or extension was considered positive. Pattern B: any reversible or irreversible perfusion abnormalities except in the septal/anteroseptal region were defined as positive. Pattern C: in the absence of fixed LV cavity dilatation, the scan was interpreted the same as pattern A, while in the presence of fixed LV cavity dilatation, only the abnormalities outside the LAD territory was defined as positive. Pattern D: as in pattern C, except that in the absence of fixed LV cavity dilatation, the scan was read according to pattern B. For all patients, the angiographic results were considered as gold standard of CAD diagnosis. Our results showed that the false positive rate of MPI in patients with fixed LV dilatation was 50%, while in cases with normal LV size or transient dilatation, was 38.5%. This difference was more prominent in the female patients. The accuracy for screening CAD for patterns A, B, C and D were 57%, 62%, 69% and 69%, respectively. Pattern D was the better approach in female cases and patients with fixed septal/anteroseptal defects. In conclusion, a) in the male population without fixed defects in the septal/anteroseptal region, the specificity and accuracy are high in all patterns and the pattern of reading does not significantly influence the diagnostic value of MPI for CAD screening. b) in LBBB patients, fixed defects limited to the septal/anteroseptal region should be considered a significant finding only when LV cavity is not dilated.

Our aim was to compare the effect of orally taken 1% diatrizoate meglumine, 5% mannitol and water before positron emission tomography/computerized tomography (PET/CT) scan on gastrointestinal tract delineation and fluorine-18-fluorodeoxyglucose ((18)F-FDG) uptake. Our methods were as follows: Sixty-one patients referred for PET/CT scan without gastrointestinal diseases were divided into three groups. One thousand mL of 1% diatrizoate meglumine was orally taken 50min before PET/CT scan in Group 1 (n=25), 1000mL 2.5% mannitol was orally taken before scan in Group 2 (n=20) and 1000mL water was orally taken before scan in Group 3 (n=16). Serum glucose and insulin were tested before and 45min after taking mannitol in Group 2 patients. Paired t test was used to compare the glucose and insulin changes. The degree of gastrointestinal filling and (18)F-FDG uptake were evaluated by three nuclear medicine physicians using a 4 grade classification standard. Kruskal-Wallis and Mann- Whitney none parametric test was used to compare the filling condition and (18)F-FDG uptake difference among the three groups and between each group. Results: the differences of serum glucose and insulin levels were not significant before and after contrast taken, in Group 2 patients. Group 2 patients had better gastrointestinal filling than patients of Group 1. Also, Group 2 patients’ gastrointestinal filling was better than in Group 3 except in rectum. The jejunum, ascending, transverse and descending colon were better filled in Group 1 patients than in Group 3 patients. The degree of (18)FFDG uptake in stomach, jejunum and ileum, in Group 2 were significantly lower than those of Group 3 (P<0.05). (18)F-FDG uptake in jejunum, in Group 1 was also lower than in Group 3 (P<0.05). (18)F-FDG uptake in ascending colon in Group 1 was higher than in Group 3 (P<0.05). (18)F-FDG uptake in transverse and descending colon, in both Group 1 and Group 2 was significantly higher than in Group 3 (P<0.05). (18)F-FDG uptake in rectum, in Group 2 was significantly higher than in Group 3 (P<0.01). The average maximum CT values in stomach, jejunum, ileum and ascending colon in Group 1 patients were: 132+/-23, 191+/-31, 313+/-47 and 374+/-53 Hounsfield units respectively (Mean+/-SD, P<0.01 between every two groups). In conclusion, patients who take iso-osmia mannitol have good gastrointestinal filling, less physiological (18)F-FDG uptake and may thus have better (18)F-FDG images displaying gastrointestinal abnormalities and differentiating pathological from physiological lesions.

Microscopic MRI (microMRI) is an emerging technique for high-throughput phenotyping of transgenic mouse embryos, and is capable of visualising abnormalities in cardiac development. To identify cardiac defects in embryos, we have optimised embryo preparation and MR acquisition parameters to maximise image quality and assess the phenotypic changes in chromodomain helicase DNA-binding protein 7 (Chd7) transgenic mice. microMRI methods rely on tissue penetration with a gadolinium chelate contrast agent to reduce tissue T(1), thus improving signal-to-noise ratio (SNR) in rapid gradient echo sequences. We investigated 15.5 days post coitum (dpc) wild-type CD-1 embryos fixed in gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) solutions for either 3 days (2 and 4 mM) or 2 weeks (2, 4, 8 and 16 mM). To assess penetration of the contrast agent into heart tissue and enable image contrast simulations, T(1) and T(*) (2) were measured in heart and background agarose. Compared to 3-day, 2-week fixation showed reduced mean T(1) in the heart at both 2 and 4 mM concentrations (p < 0.0001), resulting in calculated signal gains of 23% (2 mM) and 29% (4 mM). Using T(1) and T(*) (2) values from 2-week concentrations, computer simulation of heart and background signal, and ex vivo 3D gradient echo imaging, we demonstrated that 2-week fixed embryos in 8 mM Gd-DTPA in combination with optimised parameters (TE/TR/alpha/number of averages: 9 ms/20 ms/60 degrees /7) produced the largest SNR in the heart (23.2 +/- 1.0) and heart chamber contrast-to-noise ratio (CNR) (27.1 +/- 1.6). These optimised parameters were then applied to an MRI screen of embryos heterozygous for the gene Chd7, implicated in coloboma of the eye, heart defects, atresia of the choanae, retardation of growth, genital/urinary abnormalities, ear abnormalities and deafness (CHARGE) syndrome (a condition partly characterised by cardiovascular birth defects in humans). A ventricular septal defect was readily identified in the screen, consistent with the human phenotype. Copyright (c) 2009 John Wiley & Sons, Ltd.