Fetal brain injury

Improvements in MRI techniques widen the indications for fetal brain imaging and fetal brain injury represents the third indication of fetal brain magnetic resonance imaging (MRI) after the evaluation of suspected central nervous system (CNS) malformations and ventricular dilatation. Optimal MR imaging technique is necessary in order to collect as much data as possible about the fetal brain. Diffusion images can be used routinely in addition to the standard protocol of fetal brain MRI that consists of T1 and T2 weighted images of the fetal brain. Monovoxel proton magnetic resonance spectroscopy can also be performed in utero, but this technique is still more part of research protocol than of routine clinical protocol. Fetal brain injury includes hypoxia-ischemia, congenital infections (especially toxoplasmosis and cytomegalovirus infections), brain damage due to malformation such as vascular brain malformation and heart malformation, pregnancies at risk of fetal brain damage, and even inherited metabolic diseases, especially mitochondrial diseases. MRI findings in fetal brain injury consist of acute or chronic lesions that can be seen alone or in combination. Acute response of the fetal brain is less commonly seen than the chronic response compared to the brain response encountered in the postnatal period.     

Malignant hypertension and cerebral haemorrhage in Seckel syndrome

Seckel syndrome is an autosomal recessive condition with severe short stature and facial and neurological anomalies. Intracranial haemorrhage, due to rupture of a cerebral aneurysm, is a very rare complication of this syndrome. Malignant hypertension may play an important role in the aetiology of the aneurysm and early detection is essential in order to prevent organ damage. Conclusion:we report a new case of Seckel syndrome associated with malignant hypertension and cerebral haemorrhage.Abbreviations BA basilar artery - MCA middle cerebral artery - PICA posterior internal cerebral artery - PICU paediatric intensive care unit - SS Seckel syndrome     

Encapsulating sclerosing peritonitis: report of 2 cases

SEP is an increasingly seen complication of CAPD; we have the occasion to see again this condition because two patients came under our observation. We have remarked the unknown etiology and pathogenesis, the difficult diagnosis and therapy, and the often poor prognosis.     

Photosensitization of DNA strand breaks by three phenothiazine derivatives

The interaction and the photosensitizing activity of three phenothiazine derivatives, fluphenazine hydrochloride (FP), thioridazine hydrochloride (TR), and perphenazine (PP), toward DNA were studied. Evidences obtained from various spectroscopic studies such as fluorimetric and linear dichroism measurements indicate that these derivatives bind to the DNA at least in two ways: intercalation and external stacking on the DNA helix, depending on their relative concentrations. Irradiation of supercoiled plasmid DNA in the presence of these phenothiazines leads to single strand breaks. The DNA photocleavage appears to be due to externally bound molecules rather than to those intercalated. The highest photocleavage activity was observed with PP and TR whereas FP was less efficient. The efficiency of the photocleavage in aerated and deaerated solutions does not change thus indicating that an involvement of singlet oxygen can be excluded. Primer extension analysis of plasmid DNA irradiated in the presence of phenothiazines indicates that photocleavage of DNA occurs predominantly at Gua and Cyt residues. Laser flash experiments carried out in the presence of 2'-deoxyguanosine 5'-monophosphate reveal an efficient electron transfer between the nucleotide and the radical cations produced by photoionization of the phenothiazines. In the presence of DNA, an electron transfer process takes place within the laser pulse from the lowest singlet state of phenothiazines to the DNA bases; the time-resolved measurements showed that the back-electron transfer is a negligible decay pathway for the charged species.     

Interstitial boost and altered fractionation as novel approaches to dose escalation in the radiotherapy of glioblastoma multiforme

INTRODUCTION: The practice of image-based three dimensional treatment planning and conformal radiotherapy techniques give the opportunity to elaborate optimal treatment forms for primary brain tumours. PURPOSE: The authors examined the effect of two novel dose escalation methods on glioblastoma patients. METHODS: In nine cases they treated T1 tumours with single HDR-AL boost of 10-12 Gy dose following the conventional fractionated 60 Gy external beam radiotherapy. In fifteen patients with T2-4 tumours an intensified, hypofractionated regimen with 2.25-2.5 Gy daily and 60 Gy total dose was applied. All the treatments were carried out with image-based conformal methods. RESULTS: Majority of patients endured treatments without neurological deterioration. Transient neurotoxiticy was noticed in one and two cases, respectively. The median survival times (MST) were found to be 17 months (range: 9-25) and 12 months (range: 6-38) in the two groups, respectively. With respect to all patients, the MST was 13 months, while this value in the conventional treatment is generally considered to be 9-10 months. All the three patients who survived more than 18 months was treated with temozolamide chemotherapy as well. CONCLUSION: Based on own experience and current knowledge of authors, it seems reasonable to apply higher biological dose focal radiotherapy and chemotherapy in case of glioblastoma patients with better prognosis. To define the optimal treatment regimens randomised clinical trials should be executed.     

A study on CYP1A inhibitory action of E-2-(4'-methoxybenzylidene)-1-benzosuberone and some related chalcones and cyclic chalcone analogues

In vivo investigation of E-2-(4'-methoxybenzylidene)-1-benzosuberone (4a) on the 7,12-dimethylbenz[a]anthracene (DMBA)-induced onco/tumor suppressor gene expressions suggested that inhibition of metabolic activation of DMBA might play a role in the observed activity of the compound. In order to explore this possible biological action we have investigated whether 4a and some of its structurally related analogues had inhibitory effects on the CYP1A enzymes. During our study 7-ethoxyresorufin O-dealkylation activity of CYP1A isoenzymes was measured in liver microsomes prepared from 3-methylcholanthrene treated male rats. Inhibition constants (K(i) values) were determined by using different concentrations of 7-ethoxyresorufin and the investigated chalcones (1), E-2-benzylidene-1-indanones (2), -tetralones (3) and -benzosuberones (4). Each compound was found to be a strong competitive inhibitor of the CYP1A enzymes. Their inhibitory activity was comparable with or even higher than that of 7,8-benzoflavone, the known strong CYP1A inhibitor used as reference substance. By proper selection of the substituents on the benzylidene moiety we investigated how the inhibitory activity (K(i) value) of 1-4 varied as a function of the ring size (n=0, 5, 6, 7) carbon atoms, and the nature as well as the position of the substituents. To test applicability of the previously set structural requirements for binding of xenobiotics to the CYP1A enzymes we compared some topological, physico-chemical and quantum mechanical parameters of 1-4 with 7-ethoxyresorufin and 7,8-benzoflavone, the investigated CYP1A substrate and inhibitor, respectively.     

Indication for peritoneal biopsy in tuberculous peritonitis

BACKGROUND: With the introduction of effective antituberculous chemotherapy, the clinical outcome of tuberculous peritonitis depends much on the diagnostic accuracy of this disease entity. This review summarizes the current state-of-the-art thinking regarding the protean manifestation and diagnostic modalities of this major infectious disease. DATA SOURCES: This review was compiled after an extensive search of the current and historical literature, comprising 1,070 cases of tuberculous peritonitis. A number of important areas were highlighted, with emphasis on the diagnostic value and clinical impact of peritoneal biopsy. CONCLUSIONS: We believe an aggressive diagnostic approach, particularly with peritoneal biopsy, is warranted for the diagnosis and timely treatment of tuberculous peritonitis.     

Diffusion and perfusion MR imaging

Diffusion (DWI) and perfusion weighted (PWI) MR imaging, have come to have an increasingly important clinical role, especially in neurovascular imaging. Diffusion MR imaging does not evaluate hemodynamic parameters, but can be considered a functional technique because it provides information about the tissue functional structure at a microscopic level. In this technique, image contrast to a large extent depends on the diffusion coefficient, a parameter indicative of the characteristics of the stochastic thermic translational motion of water molecules (Brownian motion). Clinical perfusion measurement has been performed in almost all organs with different techniques. Over the last ten years, with the use of contrast media, considerable experience has been gained in the measurement of hemodynamics with MRI. At present, perfusion-MR imaging is one of the clinically most relevant procedures of functional MRI, whose application is gaining ground, owing to the increasing availability of necessary hardware and software. Physical and hemodynamic principles of the two techniques, pulse sequences necessary for their implementation and main applications in the imaging of CNS disorders are illustrated. While DWI and PWI alone can address numerous questions, their information is for the most part complementary to that provided by conventional MRI and their combination seems extremely promising.