Imaging glioma biology: spatial comparison of amino acid PET, amide proton transfer, and perfusion-weighted MRI in newly diagnosed gliomas.

PURPOSE: Imaging glioma biology holds great promise to unravel the complex nature of these tumors. Besides well-established imaging techniques such O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET and dynamic susceptibility contrast (DSC) perfusion imaging, amide proton transfer-weighted (APTw) imaging has emerged as a promising novel MR technique. In this study, we aimed to better understand the relation between these imaging biomarkers and how well they capture cellularity and vascularity in newly diagnosed gliomas. METHODS: Preoperative MRI and FET-PET data of 46 patients (31 glioblastoma and 15 lower-grade glioma) were segmented into contrast-enhancing and FLAIR-hyperintense areas. Using established cutoffs, we calculated hot-spot volumes (HSV) and their spatial overlap. We further investigated APTw and CBV values in FET-HSV. In a subset of 10 glioblastoma patients, we compared cellularity and vascularization in 34 stereotactically targeted biopsies with imaging. RESULTS: In glioblastomas, the largest HSV was found for APTw, followed by PET and CBV (p < 0.05). In lower-grade gliomas, APTw-HSV was clearly lower than in glioblastomas. The spatial overlap of HSV was highest between APTw and FET in both tumor entities and regions. APTw correlated significantly with cellularity, similar to FET, while the association with vascularity was more pronounced in CBV and FET. CONCLUSIONS: We found a relevant spatial overlap in glioblastomas between hotspots of APTw and FET both in contrast-enhancing and FLAIR-hyperintense tumor. As suggested by earlier studies, APTw was lower in lower-grade gliomas compared with glioblastomas. APTw meaningfully contributes to biological imaging of gliomas.

Increased pregenual anterior cingulate glucose and lactate concentrations in major depressive disorder.

There is ample evidence that glucose metabolism in the pregenual anterior cingulate cortex (PACC) is increased in major depressive disorder (MDD), whereas it is still unknown whether glucose levels per se are also elevated. Elevated cerebrospinal fluid (CSF) lactate concentrations in MDD patients might indicate that increased glycolytical metabolization of glucose to lactate in astrocytes either alone or in conjunction with mitochondrial dysfunction results in an accumulation of lactate and contributes to pathophysiological mechanisms of MDD. However, until now, no study investigated in vivo PACC glucose and lactate levels in MDD. Proton magnetic resonance spectroscopy was therefore used to test the hypothesis that patients with MDD have increased PACC glucose and lactate levels. In 40 healthy and depressed participants, spectra were acquired from the PACC using a maximum echo J-resolved spectroscopy protocol. Results show significant increases of glucose and lactate in patients, which are also associated with depression severity. These findings indicate impaired brain energy metabolism in MDD with increased fraction of energy utilization via glycolysis and reduced mitochondrial oxidative clearance of lactate. Targeting these metabolic disturbances might affect the balance of metabolic pathways regulating neuronal energetics and result in an attenuation of the elevated basal activity of brain regions within the neural circuitry of depression.

Formula feeding and systemic hypoxia synergistically induce intestinal hypoxia in experimental necrotizing enterocolitis.

PURPOSE: Feeding and systemic hypoxia are major stresses inducing necrotizing enterocolitis (NEC). This study aims to investigate the role of systemic hypoxia in NEC and its effect before and after feeding. METHODS: Neonatal mice were studied in three groups. Control (N = 9): breast feeding; NEC A (N = 8), gavage feeding + lipopolysaccharide (LPS) + preprandial hypoxia; and NEC B (N = 9), feeding + LPS + postprandial hypoxia. Pimonidazole, a hypoxia marker, was injected intraperitoneally before ileum was harvested for histology and quantitative RT-PCR studies. Statistical analysis was done using the ANOVA and Chi-square test. RESULTS: NEC incidence was 62.5% in NEC A and 88.9% in NEC B. The mortality in NEC B (55.6%) but not A (25%) is significantly higher than control (0%, p < 0.05). Pimonidazole staining elevated in both NEC A and B with higher pimonidazole grade in NEC B (p < 0.01). Both NEC groups had increased the expression of hypoxia-related genes: HIF-1α, GLUT-1, and PHD-3 with GLUT-1 expressed more in NEC B compared with NEC A (p < 0.01). The inflammation marker, IL6, was similarly raised in both NEC A and B. CONCLUSION: Feeding and postprandial hypoxia synergistically induce intestinal hypoxia in NEC. As feeding increases intestinal oxygen demand, maintaining a balance between intestinal oxygen supply and demand is important to prevent NEC.

Navigator based respiratory gating during acquisition and preparation phases for proton liver spectroscopy at 3 T.

Proton magnetic resonance spectroscopy ((1)H MRS) enables the non-invasive investigation of the human liver; however, because of technical difficulties it is not regularly used for diagnosis of liver diseases in clinical routine. Breathing motion is one of the major challenges, as it decreases spectral quality and leads to misplacement of the spectroscopic voxel. To overcome this problem, real-time navigator gating for spectral acquisition and preparation steps (B0 shimming, water frequency determination, receiver gain optimization, and water suppression) combined with short TE , optimized first order projection based B0 shimming, water suppression, and inner-volume saturated point resolved spectroscopy (PRESS) at 3 T is suggested. Simultaneous lipid and trimethylamine quantification is demonstrated by means of phantom, volunteer, and representative patient measurements. Precise localization of the voxel despite respiratory motion, increased spectral quality (higher signal-to-noise ratio and reduced linewidth) compared with measurements without respiratory gating, and the possibility of acquiring data without additional subject instructions regarding breathing enable robust and accurate liver (1)H MRS measurements with this novel acquisition protocol.

[Recurrent keratoconjunctivitis]. / Rezidivierende Keratokonjunktivitis.

BACKGROUND: Molluscum contagiosum is a highly infectious viral disease of the skin and mucous membranes. These lesions are found particularly often in children and young adults and are generally self-limiting. Nevertheless, molluscum contagiosum lesions in close vicinity to the eyes should be actively removed if they cause conjunctival or corneal irritation. CASE REPORT: We report the case of a 14-year-old boy who was treated for approximately 9 months for recurrent chronic keratoconjunctivitis with corneal neovascularization. Careful inspection of the eyelids revealed molluscum contagiosum. After removal of the lesions on both sides, short-term anti-inflammatory therapy and long-term surface lubrication, a gradual improvement was observed so that an almost complete visual recovery was achieved. CONCLUSION: In long-standing keratoconjunctivitis refractory to treatment, special attention should be paid to the possible presence of molluscum contagiosum, particularly in children and the lesions should be promptly removed.

Evaluation of a fall detector based on accelerometers: a pilot study.

As falls and fall-related injuries remain a major challenge in the public health domain, reliable and immediate detection of falls is important so that adequate medical support can be delivered. Available home alarm systems are placed on the hip, but have several shortcomings. A fall detector based on accelerometers and placed at head level was developed, as well as an algorithm able to distinguish between activities of daily living and simulated falls. Accelerometers were integrated into a hearing-aid housing, which was fixed behind the ear. The sensitivity of the fall detection was assessed by investigation into the acceleration patterns of the head of a young volunteer during intentional falls. The specificity was assessed by investigation into activities of daily living of the same volunteer. In addition, a healthy elderly woman (83 years) wore the sensor during the day. Three trigger thresholds were identified so that a fall could be recognised: the sum-vector of acceleration in the xy-plane higher than 2 g; the sum-vector of velocity of all spatial components right before the impact higher than 0.7 m s(-1); and the sum-vector of acceleration of all spatial components higher than 6 g. The algorithm was able to discriminate activities of daily living from intentional falls. Thus high sensitivity and specificity of the algorithm could be demonstrated that was better than in other fall detectors worn at the hip or wrist at the same stage of development.

p53- and p73-independent activation of TIGAR expression in vivo.

TIGAR (TP53-induced glycolysis and apoptosis regulator) functions as a fructose-2,6-bisphosphatase and its expression results in a dampening of the glycolytic pathway, while increasing antioxidant capacity by increasing NADPH and GSH levels. In addition to being a p53 target, p53-independent expression of TIGAR is also seen in many human cancer cell lines that lack wild-type p53. Although human TIGAR expression can be induced by p53, TAp63 and TAp73, mouse TIGAR is less responsive to the p53 family members and basal levels of TIGAR expression does not depend on p53 or TAp73 expression in most mouse tissues in vivo. Although mouse TIGAR expression is clearly induced in the intestines of mice following DNA-damaging stress such as ionising radiation, this is also not dependent on p53 or TAp73.

Comparative evaluation of fatty acids labeled with C-11, Cl-34m, Br-77, and I-123 for metabolic studies of the myocardium: concise communication.

Various long-chain fatty acids have been labeled with C-11, Cl-34m, Br-77, and I-123 and evaluated for their potential application in measuring myocardial metabolism in vivo. Comparative studies of the kinetics of accumulation and clearance from the heart muscle of mice indicate that the extraction of omega-halofatty acids is more efficient than that of alpha-halofatty acids. Among the omega-halofatty acids, the highest uptake is observed for the 17-iodoheptadecanoic acid, which shows an extraction behavior almost identical to that of [1-11C] palmitic acid, although with a higher radioactivity level in blood due to the release of free iodide.

Myocardial imaging and metabolic studies with [17-123I]iodoheptadecanoic acid in patients with idiopathic congestive cardiomyopathy.

In twenty patients with primary congestive cardiomyopathy (COCM) the patterns of accumulation and washout of the fatty acid analogue [17-123I]iodoheptadecanoic acid (I-123 HA) were studied. In contrast to patients with ischemic heart disease, where reduced I-123 HA accumulation was correlated with stenosis of the main coronary arteries, thus usually involving larger wall segments, the patients with COCM concentrated I-123 HA heterogeneously in small spotty segments throughout the entire left-ventricular myocardium. The regional washout half-times varied between 15.1 and 116.2 min. It seems that in patients with severe COCM the elimination half-times are more prolonged than in early stages of the disease. There was no correlation between the regional uptake and the elimination half-times. Sequential myocardial imaging with I-123 HA appears useful for noninvasively diagnosis of COCM.

Myocardial imaging and metabolic studies with [17-123I]iodoheptadecanoic acid.

After intravenous administration of the stearic acid analogue [17-123I]iodoheptadecanoic acid (I-123 HA), myocardial metabolism was studied in ten normal individuals, eight patients with coronary artery disease and three patients with congestive heart failure. High-quality images were obtained in sequential scintigraphy of I-123 metabolically bound in myocardial tissue. Infarcted zones as well as ischemic regions are indicated by reduced tracer uptake. Iodine-123 in the blood pool and interstitial space consists mainly of radioiodide that is liberated by fatty-acid metabolism and was corrected for. Using the proposed correction not only are the images improved but the uptake and elimination of the I-123 in the myocardial cells can be followed. The average disappearance half-time of I-123 HA from the myocardium of normal persons was 24 +/- 4.7 min. In patients with coronary artery disease significant differences between myocardial regions were observed.

17-Iodine-123 iodoheptadecanoic acid for metabolic liver studies in humans.

(17-123I)-Iodoheptadecanoic acid ([123I]HA) was used for dynamic planar scintigraphy of the liver in normal individuals (control I), in patients without liver disease but with elevated serum cholesterol and/or triglycerides (control II), and in patient groups with alcohol-induced fatty liver (PG I), fatty liver not due to alcohol (PG II), alcohol-induced liver cirrhosis (PG III), or liver cirrhosis of the posthepatitic type (PG IV). Tracer uptake and elimination time were assayed in different liver regions; mean elimination time was expressed for total liver. In control I, tracer uptake was homogeneous, and mean elimination time was 20.7 +/- 5.3 min without significant local variations. In control II, tracer uptake was reduced but homogeneous and mean elimination time was 59.4 +/- 35.8 min with some local variations. In PG I, uptake was reduced and inhomogeneous and elimination time was the same as in control I, irrespective of cholesterol and triglyceride values. In PG II, uptake was the same as in PG I but mean elimination time was 48 +/- 8.1 min with some local variations. In PG III, uptake was extremely reduced and spotty and elimination time correlated with the severity of disease from 19 to 881 min in different liver regions.

Classification and differential diagnosis of 20 problem cases of occidental malignant T-cell lymphomas.

Twenty malignant T-cell lymphomas are described in which the initial histological diagnosis was equivocal. Among lymphoma entities initially falsely interpreted on pure morphological grounds were Hodgkin's disease, lymphoepithelioid cellular lymphoma, immunoblastic lymphoma with epithelioid cells, malignant histiocytosis, histiocytosis X, centroblastic lymphoma, undifferentiated carcinoma, and undifferentiated tumour. Variations in the expected mean survival of initially diagnosed tumours and T-cell lymphomas confirm the need for immunohistological cell typing in lymphoma classification.

[Study of minimal cardiac transit times in normal persons during beta-sympathicolysis (author's transl)]. / Untersuchung über die minimalen kardialen Transitzeiten (MTTs) Herzgesunder bei beta-Sympatholyse durch Propranolol und Carazolol.

The effects of single equipotent doses of Propranolol and Carazolol on cardiac haemodynamics of normal persons were investigated in a placebo-controlled double-blind study by radiocardiographic measurements of minimal cardiac transit times (MTTs). 90 min after oral application of 40 mg Propranolol a significant (p less than 0.005) prolongation of MTTs between the right auricle and the aortic root by 25% could be observed. A corresponding effect after treatment with 5 mg Carazolol was not recognizable (p greater than 0.05). Both substances strongly reduced the heart rate. The negative chronotropic effects of both beta-blockers were indistinguishable (p greater than 0.05).

[Global and regional changes of cardiopulmonary blood volume under continuous work load (author's transl)]. / Globale und regionale kardiopulmonale Blutvolumen-Anderungen unter kontinuierlicher Belastung.

The present study describes a method for the continuous determination of global and regional stress-induced alterations of cardiopulmonary blood volumes in normals, trained athletes and patients with latent cardiac insufficiency. In contrast to normals and athletes there is an increase of the total cardiac blood volume in the cardiac patients. There are also significant differences in blood volume changes of the left lung between normals and athletes on the one hand and the cardiac patients on the other. The method is simple and non-hazardous; it permits the observation of the obviously different adaptation of the cardiopulmonary system during exercise in normals, athletes and cardiac patients.

[Studies of cardiac metabolism with 123I-labelled fatty acids and 11C-methylglucose (author's transl)]. / Stoffwechseluntersuchung am Herzen mit 123J-Fettsäuren und 11C-Methylglukose.

To characterize externally detectable changes in the myocardial metabolism of free fatty acids (FFA) and glucose, which are associated with ischemia and cardiomyopathy, omega-123I-heptadecanoic acid (stearic acid analogue), 75Br-phenylpentadecanoic acid, and 3-0-11C-methyl-D-glucose were used as indicators. It could be demonstrated that in the metabolism of free fatty acids at least two different patho-physiological situations may exist. Disturbances in the mechanism of the accumulation of free fatty acids lead to a decrease of the amount of the free fatty acids which are available for energy production (these disturbances can be recognized as indicator accumulation defects). Disturbances associated with the mechanism of free fatty acid catabolism lead to a decrease of the ability of the myocardial cell to utilize the free fatty acids (these disturbances can be recognized as changes in indicator elimination rates). Whereas in ischaemic heart disease, the areas with altered FFA accumulation correlate with the areas of altered FFA-elimination, no correlation was found in the case of cardiomyopathy. The 11C-methylglucose seems to be an excellent indicator for the in-vivo assessment of the function of transport system in the myocardial cell membrane.

Myocardial fatty acid metabolism after acute ethanol consumption.

This study was undertaken to assess the effect of ethanol ingestion on myocardial fatty acid metabolism in man. Nine individuals with informed consent and with a habitual ethanol consumption of approximately 40 g per day, but without any clinical signs of heart and metabolic disease, were examined after i.v. injection of omega-123I-heptadecanoic acid (IHA). Eight days later, these individuals were similarly examined after 2 h of continuous ingestion of a body weight dependent amount of ethanol, which was calculated to produce a blood level of 100 mg per 100 ml (1%). Then the subjects had been asked to reduce their ethanol consumption rigorously for 15 months. Subsequently after 2 weeks of abstinence a follow-up investigation without ethanol loading was carried out. The investigations were performed with an Anger scintillation camera in LAO-45 degrees projection. The measurement period was 40 min. Tracer accumulation and regional elimination half-times of IHA were analysed. In all patients, acute ethanol loading produced significant changes in pattern of accumulation and/or regional elimination half-times. Ethanol-induced alterations in segmental accumulation did not appear to be predictably correlated with changes in segmental elimination half-times. After rigorous reduction of ethanol consumption followed by 2 weeks of abstinence a normalization of the tracer uptake was observed; the distribution pattern was almost homogeneous. Also the regional elimination half-times became normal. The data demonstrate the significant effects of both chronic ethanol consumption and particularly acute ethanol loading on myocardial fatty acid metabolism and the reversibility of the effects.

Trace element concentration in the human pineal body. Activation analysis of cobalt, iron, rubidium, selenium, zinc, antimony and cesium.

100 human pineal bodies (56 male and 44 females) were analyzed by means of instrumental neutron activation analysis for trace concentrations of cobalt, iron, rubidium, selenium, zinc, antimony and cesium. The results indicated that the measured element concentrations are not related to body-surface, age and fresh weight. Moreover, the mean absolute cobalt value from 97 pineal bodies is increased by a factor of 1.43 over the mean absolute concentration value of 257 other areas of the brain. The mean zinc content is found to be 3.7 fold higher than the mean zinc value from 269 other samples of brain. The iron values from various brain areas do not differ from those of the pineal body. Compared to other brain regions pineal selenium is increased and rubidium is decreased. Correlating the different element concentrations to each other, a positive correlation is found for selenium and ribidium, a negative correlation for cobalt and zinc. The present data suggest that the measured trace elements are somehow related to specific roles in the physiology and biochemistry of the pineal body. This is supported by the constancy of element concentration over a wide range of increasing fresh weights of the organ. It is considered that zinc, cobalt and iron are involved as constituents of enzymes in the metabolism of amino acids, peptides and proteins of the pineal body. Moreover the conspicuous high zinc content of this organ may be related to a so far undetected neurotransmitter.

Trace elements in brains of patients with alcohol abuse, endogeneous psychosis and schizophrenia.

The concentrations of Co, Fe, Rb, Se and Zn were analysed, by means of neutron activation analysis, in the brains of three patients with alcohol abuse, of one patient with endogeneous psychosis and of one patient with schizophrenia. The patients with alcohol abuse suffered from the Wernicke-Korsakoff syndrome. The data were compared with results from brains which were not diseased ("normals"). Patients with alcohol abuse had diminished values of rubidium in nearly all analysed samples of cerebral nuclei (greater than 30% compared to normals), whereas the Rb values were normal or diminished in cortical regions. The cobalt values were reduced (greater than 20%) in eight out of 14 nuclei and in five out of nine cortical regions. Differences in the Fe and Se values were mainly located in the cerebral nuclei. In the caudate nucleus the patient with endogeneous psychosis had highly significant elevated values of all analysed elements. The element concentrations of the patient with schizophrenia did not significantly differ from those of normal controls. The loss of nearly all elements was conspicuous in those regions which show neuro-pathological cell degeneration or atrophy in the case of Wernicke-Korsakoff syndrome. This loss of element concentrations in patients with alcohol abuse is interpreted as a loss of cellular vitality.

Does the posterior sagittal approach with perirectal dissection impair fecal continence in a normal rectum?

The aim of this study was to determine, using human material and animal experiments, whether the posterior sagittal approach with perirectal dissection (PSAPD) in patients with an intact anorectum is a suitable means of exposure for the correction of complicated anomalies of the genitourinary tract without impairment of fecal continence. Over the last 6 years, the authors have performed PSAPD in seven children with an intact anorectum. At the time of operation, their ages ranged from 8 months to 14 years. All patients showed normal fecal continence at the end of follow-up (averaging 32 months). Only after completion of the study did the authors read that Peña et al had found that PSAPD provoked severe changes in bowel control in dogs. This contradiction prompted the authors to repeat the animal experiments, and they could not reproduce the favorable results obtained in children. This might be explained by the following factors: the surgical dissection used in the dogs was more extensive, anatomic differences between man and dog, the relatively much younger age of the animals (versus the patients), and the shorter follow-up and lack of educability of the dogs. The authors conclude that PSAPD is a suitable approach for selected lesions of the genitourinary tract in children who have a normal rectum and it does not impair fecal continence.

[Ambulatory pediatric surgery--from the parents' view]. / Ambuláns gyermeksebészet--ahogy a szülök látják.

In recent years "day-care surgery" has been the treatment of choice for an ever increasing number of paediatric surgical patients in countries with an efficient Health Service. The reasons for this are the decreased psychological trauma to the children and the dramatic fall in expenses. In view of the important role played by parental attitude in the spreading of day-care surgery, nearly 200 parental opinions about day-care surgery have been studied. From them it became clear that the parents were convinced of advantages of this form of treatment over the conventional form requiring longer hospitalization. The authors believe that nowadays "day-care surgery" should be resorted to in the majority of a well circumscribed group of paediatric surgical conditions, from which both child and parents, and also our National Health Service will benefit.