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.     

Immune system alterations in lung cancer patients

The immune system plays an important role in the defense against neoplastic disease and immune responses show temporal changes related to circadian variations of antibodies, total lymphocytes in the peripheral blood and cell mediated immune responses. In this study we evaluate. lymphocyte subpopulations and interleukin-2 (IL-2) serum levels in peripheral blood samples collected at four-hour intervals for 24-hours starting at 06.00 h from ten healthy subjects aged 65-79 years (mean age +/- s.e. 67.28 +/- 3.11) and from ten subjects suffering from untreated non small cell lung cancer aged 65-78 years (mean age +/- s.e. 68.57 +/- 1.81). Areas under the curve, mean diurnal levels (mean of 06.00-10.00-14.00 h) and mean nocturnal levels (mean of 18.00-22.00-02.00 h) were calculated, and the presence of circadian rhythmicity was evaluate. When we compared AUC values there was a decrease in CD8bright (T suppressor subset) and an increase in CD16 (natural killer cells) and of IL-2 serum levels in cancer patients. When we compared mean diurnal levels, CD8 (T suppressor/cytotoxic subset) and CD8bright levels were lower, and CD16 levels were higher in cancer patients. When we compared mean nocturnal levels, CD16 and CD25 (T and B activated lymphocytes with expression of the a chain of IL-2 receptor) levels were higher, while CD8, CD8bright, CD20 (total B-cells), TcRd1 (epitope of the constant domain of d chain of T-cell receptor 1) and dTcS1 (epitope of the variable domain of d chain of T-cell receptor1) levels were lower in cancer patients. A clear circadian rhythm was validated for the time-qualified changes in CD4, CD20, HLA-DR with acrophase at night, and CD8, CD8 bright, CD8 dim, CD16, TcRd1 and dTcS1 with acrophase in the morning in the control group. A clear circadian rhythm was validated for the time-qualified changes in CD4 with acrophase at night, in the group of cancer patients. Results obtained in our study show that lung cancer is associated with anomalies of proportion and circadian variations of lymphocyte subsets that must be considered when adoptive immunotherapy has to be planned.     

Intracranial hemorrhage at the onset of thrombotic thrombocytopenic purpura in an infant: therapeutic approach and intensive care management

Thrombotic thrombocytopenic purpura (TTP) is quite rare in infancy and must be treated intensively as a life-threatening disease. Diffuse vascular thromboses may occur, and neurologic involvement is a cornerstone of the diagnosis of TTP. We describe a case of an infant who presented with a sudden cerebral hemorrhage and subsequently developed the typical clinical features of TTP. Emergency treatment in the Pediatric Intensive Care Unit (PICU) consisted of plasma therapy and exchange-transfusion (EXT) to arrest the intravascular process and the exsanguinating blood loss. Exchange-transfusion is a life-saving procedure that is rarely performed after the neonatal age.     

Association of high serum creatinine and anemia increases the risk of coronary events: results from the prospective community-based atherosclerosis risk in communities (ARIC) study

Coronary heart disease (CHD) is a major cause of morbidity and mortality in patients with chronic kidney disease or anemia. The purpose of this study was to examine whether the association between renal function and risk of CHD is modified by hemoglobin (Hgb) status. Analyses were based on data from the Atherosclerosis Risk in Communities study, a community-based study of risk factors for CHD in middle-aged people. People with known CHD at baseline were excluded from the analysis. Participants were followed for 9 yr for the occurrence of CHD. Anemia was defined as Hgb <13 g/dl in men and <12 g/dl in women. Cox proportional hazards models were used to assess the relative risk (RR) of CHD occurrence according to Hgb status, after adjusting for other risk factors (demographics, lipids, diabetes, hypertension, smoking, body mass index, and carotid intima-media thickness). A total of 13,329 participants were included. The interaction between Hgb concentration and serum creatinine (Scr) was significant (P = 0.02). Among people with anemia, a Scr >/=1.2 mg/dl in women or >/=1.5 mg/dl in men was associated with a higher risk of CHD (RR, 2.74; 95% confidence interval, 1.42 to 5.28) than those with normal Scr. In contrast, among those without anemia, this association was not noted (RR, 1.20; 95% confidence interval, 0.86 to 1.67). In conclusion, this study indicates that high Scr is associated with almost a threefold risk of CHD among middle-aged people with anemia, whereas no increased risk is found in people with high Scr in the absence of anemia.     

Rhodococcus equi peritonitis in continuous ambulatory peritoneal dialysis

The human Rhodococcus equi (R. equi) infection is now emerging, although extrapulmonary manifestation and isolation from patients without human immunodeficiency virus (HIV) infection remains unusual. Considerable effort is required to correctly identify and diagnose this facultative pathogen in patients with peritonitis in end-stage renal failure (ESRF) on continuous ambulatory peritoneal dialysis (CAPD). In the six cases of R. equi CAPD peritonitis reported in this series, diagnoses were made, on average, after 15 days and prolonged antibiotic therapy with morbidity in two patients. A diagnosis of R. equi should be considered in patients with suspected diphtheroid or Nocardia CAPD peritonitis, even with no history of animal contact. This study is the largest series on R. equi CAPD peritonitis and highlights the impact of this disease.     

Potency and specificity of the pharmacological action of a new,antiasthmatic, topically administered soft steroid,etiprednol dicloacetate (BNP-166)

In the present study, the pharmacological effects of etiprednol dicloacetate (BNP-166; ethyl-17alpha-dichloroacetoxy-11beta-hydroxyandrosta-1,4-diene-3-one-17beta-carboxylate), a new soft steroid, intended to use for the treatment of asthma, were investigated in an animal model of allergen sensitized and challenged Brown Norway rats using local treatment. The examinations involved the determination of the effect of the compound on the extent of allergen induced broncho-alveolar fluid and lung tissue eosinophilia, goblet cell hyperplasia and mucus production, perivascular edema formation, and airways hyperresponsiveness. The activity of etiprednol dicloacetate was compared with that of budesonide. Using in vitro methods, the soft character of etiprednol dicloacetate was investigated together with its capability to dissociate transrepressing and transactivating properties. We found that combining all the examined parameters etiprednol dicloacetate was at least equipotent with budesonide in the animal model, but in several investigated variables it surpassed the activity of budesonide. The effect of etiprednol dicloacetate in vitro was shown to be the function of the quantity of the serum, present in the assay, it was also strongly affected by the incubation time and decreased significantly when it was preincubated with human plasma. These features are characteristics of a soft drug that is quickly inactivated in the systemic circulation. In addition, it was revealed that while the transrepressing potential of etiprednol dicloacetate remained high, its transactivating activity was greatly reduced. These data indicate that the strong local effect of the compound will very likely be accompanied with a significantly reduced systemic activity predicting favorable selectivity in the pharmacological action of etiprednol dicloacetate.