Fully automated analysis combining [18F]-FET-PET and multiparametric MRI including DSC perfusion and APTw imaging: a promising tool for objective evaluation of glioma progression.

PURPOSE: To evaluate diagnostic accuracy of fully automated analysis of multimodal imaging data using [18F]-FET-PET and MRI (including amide proton transfer-weighted (APTw) imaging and dynamic-susceptibility-contrast (DSC) perfusion) in differentiation of tumor progression from treatment-related changes in patients with glioma. MATERIAL AND METHODS: At suspected tumor progression, MRI and [18F]-FET-PET data as part of a retrospective analysis of an observational cohort of 66 patients/74 scans (51 glioblastoma and 23 lower-grade-glioma, 8 patients included at two different time points) were automatically segmented into necrosis, FLAIR-hyperintense, and contrast-enhancing areas using an ensemble of deep learning algorithms. In parallel, previous MR exam was processed in a similar way to subtract preexisting tumor areas and focus on progressive tumor only. Within these progressive areas, intensity statistics were automatically extracted from [18F]-FET-PET, APTw, and DSC-derived cerebral-blood-volume (CBV) maps and used to train a Random Forest classifier with threefold cross-validation. To evaluate contribution of the imaging modalities to the classifier's performance, impurity-based importance measures were collected. Classifier performance was compared with radiology reports and interdisciplinary tumor board assessments. RESULTS: In 57/74 cases (77%), tumor progression was confirmed histopathologically (39 cases) or via follow-up imaging (18 cases), while remaining 17 cases were diagnosed as treatment-related changes. The classification accuracy of the Random Forest classifier was 0.86, 95% CI 0.77-0.93 (sensitivity 0.91, 95% CI 0.81-0.97; specificity 0.71, 95% CI 0.44-0.9), significantly above the no-information rate of 0.77 (p = 0.03), and higher compared to an accuracy of 0.82 for MRI (95% CI 0.72-0.9), 0.81 for [18F]-FET-PET (95% CI 0.7-0.89), and 0.81 for expert consensus (95% CI 0.7-0.89), although these differences were not statistically significant (p > 0.1 for all comparisons, McNemar test). [18F]-FET-PET hot-spot volume was single-most important variable, with relevant contribution from all imaging modalities. CONCLUSION: Automated, joint image analysis of [18F]-FET-PET and advanced MR imaging techniques APTw and DSC perfusion is a promising tool for objective response assessment in gliomas.

[Importance of FDG-PET/computed tomography in colorectal cancer]. / Stellenwert der FDG-PET/Computertomographie beim kolorektalen Karzinom.

BACKGROUND: Hybrid imaging FDG PET/CT (18F­fluordeoxyglucose positron emission tomography/computed tomography) has gained increasing importance in oncology in recent years. DIAGNOSIS: A focal increase in FDG uptake in the gastrointestinal tract may be due to colorectal carcinoma. Such a finding requires further clarification. PRIMARY STAGING: Staging of the primary and locoregional lymph nodes remains a domain of established imaging modalities as FDG PET/CT does not provide a clear additional benefit. Liver metastases can be detected with high sensitivity by FDG PET/CT, but MRI is superior in small lesions. RADIATION THERAPY PLANNING: So far FDG PET/CT plays a subordinate role in the radiation therapy planning of rectal cancer. However, it can potentially contribute to the optimization of planning target volumes. THERAPY MONITORING: FDG PET/CT is suitable for monitoring therapy because morphological and metabolic changes of the tumor can be detected in early stages. This enables early detection of nonresponders after beginning neoadjuvant chemoradiation therapy of rectal cancer. FDG PET/CT can also be used for therapy control of liver metastases, especially after local therapeutic procedures. DETECTION OF RECURRENCE: With clinical suspicion of local recurrence and increased tumor markers, FDG PET/CT is a valuable tool as tumor recurrence can be detected with high sensitivity and specificity.

Human basophils are a source of - and are differentially activated by - IL-31.

BACKGROUND: Basophils are important effector cells involved in the pathogenesis of inflammatory skin diseases including chronic urticaria which is associated by increased IL-31 serum levels. So far the effects of IL-31 on human basophils are unknown. OBJECTIVE: To analyse the functional role of IL-31 in basophil biology. METHODS: IL-31 expression was evaluated in skin samples derived from chronic spontaneous urticaria patients. Oncostatin M receptor (OSMR), IL-31 receptor A (RA) and IL-31 protein expressions were analysed on human basophils from healthy donors. Basophil responses to IL-31 were assessed for chemotaxis, externalization of CD63 and CD203c as well as the release of histamine, IL-4 and IL-13. RESULTS: IL-31RA and OSMR were expressed on human basophils. IL-31 was strongly expressed in the skin of patients with chronic spontaneous urticaria and was released from isolated basophils following either anti-IgE, IL-3 or fMLP stimulation. IL-31 induced chemotaxis and the release of IL-4 and IL-13 which was specifically inhibited by anti-IL-31RA and anti-OSMR. Conversely, IL-31 had no effect on CD63 and CD203c externalization or histamine release. CONCLUSIONS AND CLINICAL RELEVANCE: Human basophils are a source of -and are activated by - IL-31 with the release of pro-inflammatory cytokines and the induction of chemotaxis indicating an important novel function of IL-31 in basophil biology.

Regulation of melanocortin 1 receptor in allergic rhinitis in vitro and in vivo.

BACKGROUND: α-melanocyte-stimulating hormone (α-MSH) was shown to inhibit allergic airway inflammation and exert suppressive effects on human basophils. OBJECTIVE: This study aims to extend our current knowledge on the melanocortin 1 receptor (MC1R) expression in nasal tissue of patients with allergic rhinitis (AR) and functional effects of α-MSH in human basophils especially from patients with allergic rhinitis. METHODS: MC1R expression before and after nasal allergen provocation was studied in nasal mucosal tissue of AR patients and in a mouse model of allergic airway inflammation using immunofluorescence. In vitro regulation of the MC1R and CD203c surface expression on whole-blood basophils of patients with AR and controls was assessed with flow cytometry. Functional effects of α-MSH on isolated basophils were analysed regarding apoptosis with flow cytometry and chemotaxis using a Boyden chamber assay. RESULTS: We detected an accumulation of MC1R-positive basophils in nasal mucosa tissue of patients with AR 24 h after nasal allergen provocation. Such accumulation was not present in mucosa sections from healthy controls. In mice with allergic airway inflammation, we found a clear accumulation of MC1R-positive basophils in the nasal tissue compared to control mice. MC1R expression was inducible in AR patients and controls by stimulation with anti-IgE. α-MSH inhibited anti-IgE and grass pollen induced upregulation of CD203c, but had no effect on chemotaxis or apoptosis of basophils in vitro. CONCLUSIONS AND CLINICAL RELEVANCE: MC1R-positive basophils accumulate in the nasal mucosa of patients with AR after nasal allergen provocation. Since α-MSH suppresses proinflammatory effector functions in human basophils via the MC1R, it constitutes an interesting novel target for modulating the allergic inflammatory response.

Human basophil chemotaxis and activation are regulated via the histamine H4 receptor.

BACKGROUND: IgE-mediated cross-linking of FcεRI results in the release of mediators stored in basophil granules, such as histamine and proteases, and in the de novo synthesis of sulfidoleukotrienes. OBJECTIVE: In this study, we investigated the role of the histamine receptors, in particular that of the histamine H4 receptor (H4R), in modulating human basophil function. METHODS: The mRNA expression of the histamine receptors was measured by real-time PCR. Migration of basophils was assessed using the modified Boyden chamber technique. The expression levels of CD63 and CD203c on the cell surface and the sulfidoleukotriene release were determined by flow cytometry and ELISA, respectively. RESULTS: We could show that highly purified basophils express the H1R, H2R, and H4R but not the H3R mRNA. Human basophils expressed higher H4R mRNA levels as compared to the expression levels of the H1R (P < 0.01). Histamine and the H4R agonist ST-1006 initiated active migration of basophils (P < 0.001). A significant reduction in FcεRI cross-linking-mediated surface expression of CD63 and CD203c was observed on basophils after pre-incubation with histamine or the specific H4R agonist ST-1006 (P < 0.01). The synthesis and release of sulfidoleukotrienes from basophils after activation with different stimuli, by FcεRI cross-linking or by stimulation with hymenoptera venom allergens, were significantly reduced by histamine or the H4R agonist ST-1006 (P < 0.05-0.001). CONCLUSION: These data imply that the H4R regulates IgE-dependent processes in human basophils and provides a novel function of the H4R preventing an overwhelming immune reaction by engagement of a negative feedback loop.

Cimicifuga racemosa dried ethanolic extract in menopausal disorders: a double-blind placebo-controlled clinical trial.

OBJECTIVES: To compare the efficacy and safety of the black cohosh root extract Cr 99 with placebo in women with climacteric complaints. METHODS: A multicenter, randomized, placebo-controlled, double-blind, parallel group study was conducted in 122 menopausal women (intention-to-treat population) with > or =3 hot flashes a day, treated over 12 weeks. Two main efficacy measures - weekly weighted score of hot flashes and Kupperman Index - and secondary efficacy variables, e.g. Menopause Rating Scale, were defined. Routine safety laboratory parameters and adverse events were documented. RESULTS: The primary efficacy analysis showed no superiority of the tested black cohosh extract compared to placebo. However, in the subgroup of patients with a Kupperman Index> or =20 a significant superiority regarding this index could be demonstrated (P<0.018). A decrease of 47% and 21% was observed in the black cohosh and placebo group, respectively. The weekly weighted scores of hot flashes (P<0.052) and the Menopause Rating Scale (P<0.009) showed similar results. Prevalence and intensity of the adverse events did not differ in the two treatment groups. CONCLUSIONS: The results indicate a superiority of the tested Cimicifuga racemosa extract compared to placebo in patients with menopausal disorders of at least moderate intensity according to a Kupperman Index > or =20, but not in the intention-to-treat population as a whole.

Effects of incremental infusions of atrial natriuretic factor on aldosterone, renin, and blood pressure in humans.

To evaluate the physiological effects of human atrial natriuretic factor-(99-126) (ANF), we infused ANF, 0.1, 0.3, and 1.0 micrograms/min, or placebo for 125 minutes on different days into six sodium-deprived normal men. During the last 45 minutes of infusion, angiotensin II, 6 ng/kg/min, was infused. Blood pressure, heart rate, plasma concentrations of ANF, aldosterone, and cortisol, and plasma renin activity (PRA) were measured before and during infusion. Steady state mean plasma ANF levels during infusion were 26.2 (placebo), 68.8 (0.1 micrograms ANF/min), 221 (0.3 micrograms ANF/min), and 648 pg/ml (1.0 microgram ANF/min). Systolic blood pressure fell significantly (with 1.0 microgram ANF/min), and diastolic pressure tended to rise in a dose-dependent manner, while heart rate was unchanged. PRA and plasma aldosterone fell during ANF infusion in a dose-dependent manner (significant with 0.3 and 1.0 microgram ANF/min infused). The blood pressure-raising and aldosterone-stimulating effects of angiotensin II were blunted by ANF (significant only with 1.0 microgram ANF/min). It is concluded that effects of ANF on blood pressure and the renin-aldosterone system occur with plasma ANF levels close to the physiological range, as well as with slightly elevated ANF levels, as observed in congestive heart failure and renal insufficiency.

Analysis of chronic lymphoid leukaemias according to FAB.

We have studied the immunophenotypic features in patients with chronic lymphoid leukaemia and investigated the suitability of classification according to guidelines of the French-American-British (FAB) group. Immunophenotyping was carried out on cytocentrifuge preparations of mononuclear blood leukocytes using the alkaline phosphatase-antialkaline phosphatase (APAAP) method. The 114 leukaemias, including 58 cases of B-chronic lymphocytic leukaemia (B-CLL), 3 Waldenström's macroglobulinaemia, 6 prolymphocytic leukaemia (B-PL), 13 B-CLL/PL, 4 B-CLL of mixed cell type, 8 splenic lymphoma with villous lymphocytes (SLVL), 8 hairy cell leukaemia (HCL), two HCL variant, three leukaemic phase of follicular lymphoma, two leukaemic phase of intermediate lymphoma, two plasma cell leukaemia and two chronic T-cell leukaemia, were investigated. The 111 of 112 B-chronic lymphoid leukaemias (B-CLL + B-PL + B-CLL/PL + SLVL + HCL etc.) showed monotypic light chains. The antibody HML1 was highly specific for HCL. The antibodies CD11c and CD25 were positive in all HCL cases, but were not specific for this disease. CD5 positivity and CD22s negativity were found in most patients with B-CLL, B-CLL/PL and B-CLL of mixed type. This marker type has a limited value for differentiation from the other chronic lymphoid leukaemias. We also studied three patients with chronic lymphoid leukaemia which were not described by the FAB classification. We conclude that a study of the morphology of the leukaemic cells was the most useful basis for the diagnosis of these leukaemias, whereas immunotyping was apparently valuable only in individual cases.

High-dose chemotherapy with carboplatin, etoposide and ifosfamide followed by autologous stem cell rescue in patients with relapsed or refractory malignant lymphomas: a phase I/II study.

Patients with relapsed or refractory non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) with recurrences after an anthracyclin-containing regimen only have a chance of cure of below 10% with conventional chemotherapy. In order to improve their prognosis, we started a phase I/II trial using high-dose therapy comprising carboplatin, together with etoposide and ifosfamide (CEI), followed by autologous stem cell rescue (ASCR) as consolidation after salvage treatment. Since September 1990, 40 patients with intensively pretreated advanced NHL (n = 24) or HD (n = 16) received one cycle of high-dose therapy (HDT) consisting of carboplatin 1500 mg/m2, ifosfamide 10 g/m2 and etoposide in escalating doses from 1200 mg/m2 to 2400 mg/m2 followed by ASCR. Thirty-nine patients were assessable for toxicity and response. The following doses appeared to be safe: carboplatin 1500 mg/m2, etoposide 2400 mg/m2 and ifosfamide 10 g/m2. All patients developed grade 3 nausea and grade 3 or 4 mucositis. Granulocytopenic fever occurred in 100% with grade 4 infections in 15%. Mild transient kidney toxicity was noted in 36% and liver toxicity in 20% of patients. One toxic death occurred (2.5%). Objective responses were obtained in 36 of 39 patients (92%) with complete remissions (CR) in 24 patients (61.5%) and partial remissions (PR) in 12 (30.7%). Median observation time for surviving patients was 23.3 months (range 3.4-52.3). The probabilities of overall, event-free and relapse-free survival at 2 years are 62, 39 and 55%, respectively. Patients with primary refractory disease or resistant relapse had a poor prognosis. High-dose carboplatin, etoposide and ifosfamide plus autologous stem cell rescue represents an effective, potentially curative salvage treatment with acceptable toxicities.

Water: an essential but overlooked nutrient.

Water is an essential nutrient required for life. To be well hydrated, the average sedentary adult man must consume at least 2,900 mL (12 c) fluid per day, and the average sedentary adult woman at least 2,200 mL (9 c) fluid per day, in the form of noncaffeinated, nonalcoholic beverages, soups, and foods. Solid foods contribute approximately 1,000 mL (4 c) water, with an additional 250 mL (1 c) coming from the water of oxidation. The Nationwide Food Consumption Surveys indicate that a portion of the population may be chronically mildly dehydrated. Several factors may increase the likelihood of chronic, mild dehydration, including a poor thirst mechanism, dissatisfaction with the taste of water, common consumption of the natural diuretics caffeine and alcohol, participation in exercise, and environmental conditions. Dehydration of as little as 2% loss of body weight results in impaired physiological and performance responses. New research indicates that fluid consumption in general and water consumption in particular can have an effect on the risk of urinary stone disease; cancers of the breast, colon, and urinary tract; childhood and adolescent obesity; mitral valve prolapse; salivary gland function; and overall health in the elderly. Dietitians should be encouraged to promote and monitor fluid and water intake among all of their clients and patients through education and to help them design a fluid intake plan. The influence of chronic mild dehydration on health and disease merits further research.

Metabolic profiles, diet, and health practices of championship male and female bodybuilders.

To obtain a more complete view of their general health and health care habits, 27 bodybuilders (19 men and 8 women) competing at the 1988 National Physique Committee's Junior USA Bodybuilding Championships participated in this study. Data pertaining to demographics and pre-competition nutrition, training, health, and drug abuse practices were collected by self-administered and interview surveys and records. Anthropometric and blood pressure measurements and casual blood samples were collected on -site at the competition registration. Multi-drug abuse was reported by 15% to 40% of the subjects, and 20% to 40% of subjects left the drug use questions unanswered. Severe fluid restrictions and dehydrating practices were reported by all subjects. Eleven men and two women agreed to have blood drawn. Plasma glucose values were at the low end of the normal fasting range. Hemoglobin levels were elevated, indicating hypohydration; magnesium levels were slightly low. Percent body fat, estimated by seven-site skinfold measures, was low for both sexes (men, 6.0 +/- 1.8; women, 9.8 +/- 1.5); 75% of the women reported normal menstrual cycles. The men reported high-protein, low-fat hypocaloric diet patterns. Women had a moderate zinc intake and a remarkably deficient calcium intake despite an adequate energy intake. This research demonstrates that bodybuilders partake in a multitude of practices that may place them in high-risk health categories. It is essential that health care workers in contact with bodybuilding athletes intervene and educate them about healthy dietary and training alternatives.

The effects of anabolic steroids and strength training on the human immune response.

The immune response was assessed in 13 competitive bodybuilders self-administering anabolic-androgenic steroids and ten competitive bodybuilders not administering these drugs. Laboratory assessment included the number and relative distribution of T-cells, T-helper/inducer cells, T-cytotoxic/suppressor cells, activated T-cells, lymphocyte transformation to the mitogens, pokeweed mitogen (PWM), phytohemagglutinin (PHA), Concanavalin-A (CON-A), Staphylococcus aureus Cowan strain I (SAC), serum immunoglobulins, and natural killer (NK) activity. There were no significant differences in T-cell subsets among steroid users and non-users, but lymphocyte transformation studies revealed that the anabolic-androgenic steroid-using group had enhanced proliferative ability to the B-cell mitogen, SAC, in comparison to non-bodybuilding controls. NK activity was significantly (P less than 0.05) augmented in the anabolic-androgenic steroid users but not in the non-using bodybuilders. Serum immunoglobulin levels, in particular IgA, were significantly (P less than 0.017) lower in the steroid-using group. Four of 13 steroid users and three of eight non-steroid-using bodybuilders had detectable antinuclear antibodies. These studies indicate that 1) anabolic-androgenic steroid use as practiced by contemporary athletes is a potent modulator of immune responsiveness and 2) autoantibodies are prevalent in strength-trained men even in the absence of anabolic steroid use.

Amenorrhoea, sterility and hyperprolactinaemia. Importance of complex movement tomographic x-ray study and follow-up of the sella turcica.

In a 24 y.o. woman complaining of primary amenorrhoea and infertility, hyperprolactinaemia and clearly enlarged sella turcica on standard x-rays in 1975 led to the diagnosis of a pituitary prolactin-producing adenoma, later confirmed surgically. Galactorrhoea never occurred spontaneously and could not be provoked at physical examination. In the course of a previous investigation in 1967, the standard x-ray of the sella turcica, although showing already a minor duplication of the anterior wall of the sella, had been misinterpreted as being normal. It is clear from the present observation that repeated, for example at yearly intervals, radiological examinations and prolactin determinations (not available before 1971) would allow an early diagnosis. It is furthermore stressed that a tomographic radiological examination using complex movement (spiral or hypocycloidal) should be mandatory in any case of amenorrhoea with hyperprolactinaemia in order to assess or not the possible existence of a prolactin-producing pituitary adenoma. Indeed, dynamic studies of anterior pituitary secretions cannot allow a differential diagnosis between tumoural and functional hyperprolactinaemia.

Nucleus basalis magnocellularis and pedunculopontine tegmental nucleus: control of the slow EEG waves in rats.

Certain human disorders, which are characterized by learning and memory disturbances, are also accompanied by synchronizations of the cortical electroencephalogram (EEG). Although the EEG synchronization was casually related to the degeneration of the cholinergic basal forebrain, degenerations were found also in the cholinergic pontomesencephalic tegmentum. The present study was carried out to prove whether lesions of rat's pedunculopontine tegmental nucleus (PPTg) may cause EEG synchronizations like lesions of the basal forebrain. The effects of the unilateral ibotenic acid lesions of the nucleus basalis magnocellularis (NBM) and of the PPTg on the frontal and occipital EEG were compared in different behavioural states. The NBM lesion caused unilateral spectral power increases of all frequencies up to 20 Hz in the frontal EEG that were stronger with increased arousal level. Additionally, synchronized spike and wave discharges appeared in the frontal EEG. The NBM may suppress especially the delta EEG waves in the frontal motor cortex during motor active behaviours. The PPTg lesion caused unilateral suppressions of the occipital theta rhythm during exploratoring sniffing. During grooming the power of the frontal delta waves were elevated. Furthermore, the PPTg lesion caused a suppression of slow sleep waves. The results may indicate that a degeneration of both brain regions may change differently the power of the cortical slow EEG waves.

Fruits and veggies: are you getting enough of a good thing?

You've probably been hearing it since grade school: Eat your fruits and vegetables and you'll be healthy. Sometime between then and now, you may have grown skeptical of that advice. It seems too simplistic. Human health and nutrition science must be more complicated than that, right?

Antioxidant answers.

It seems like the more things change, the more they stay the same. For decades, dietitians told you to eat a balanced diet of a variety of foods and to eat in moderation. Then came news that antioxidants may help your body function better, prevent certain diseases, and relieve muscle damage and soreness after exercise. Dietitians wondered if eating whole foods was not enough and whether you should supplement your diet with antioxidants.

Fiber Fundamentals: Up-to-Date Answers to Common Questions.

Some of the most common nutrition questions are about fiber: "Am I eating enough?" "How do I get more?" "Don't only older people have to worry about fiber?" "I don't have bowel problems-why do I need more fiber?" "Won't a high-fiber diet make me too full to exercise?" Because research continues to confirm fiber's benefits, here are up-to-date answers and practical ways you can increase the fiber in your diet.

Sense and food sensitivity: coping with allergies and food intolerance.

When you're used to being active, there's nothing worse than being pinned down by a recurring upset stomach or cold. You might assume you have a virus, but sometimes these recurrences can be signs of food allergies or, more likely, food intolerances.

Food safety for your active summer.

Leading an active life often means eating on the go, especially in summer. But just as summer weather helps our gardens grow, it makes the growing easy for bacteria that can cause foodborne illnesses or food poisoning.