Multiparametric human hepatocellular carcinoma characterization and therapy response evaluation by hyperpolarized 13C MRSI

Individual tumor characterization and treatment response monitoring based on current medical imaging methods remain challenging. This work investigates hyperpolarized ¹³ C compounds in an orthotopic rat hepatocellular carcinoma (HCC) model system before and after transcatheter arterial embolization (TAE). HCC ranks amongst the top six most common cancer types in humans and accounts for one‐third of cancer‐related deaths worldwide. Early therapy response monitoring could aid in the development of personalized therapy approaches and novel therapeutic concepts. Measurements with selectively ¹³ C ‐labeled and hyperpolarized urea, pyruvate and fumarate were performed in tumor‐bearing rats before and after TAE. Two‐dimensional, slice‐selective MRSI was used to obtain spatially resolved maps of tumor perfusion, cell energy metabolic conversion rates and necrosis, which were additionally correlated with immunohistochemistry. All three injected compounds, taken together with their respective metabolites, exhibited similar signal distributions. TAE induced a decrease in blood flow into the tumor and thus a decrease in tumor to muscle and tumor to liver ratios of urea, pyruvate and its metabolites, alanine and lactate, whereas conversion rates remained stable or increased on TAE in tumor, muscle and liver tissue. Conversion from fumarate to malate successfully indicated individual levels of necrosis, and global malate signals after TAE suggested the washout of fumarase or malate itself on necrosis. This study presents a combination of three ¹³ C compounds as novel candidate biomarkers for a comprehensive characterization of genetically and molecularly diverse HCC using hyperpolarized MRSI, enabling the simultaneous detection of differences in tumor perfusion, metabolism and necrosis. If, as in this study, bolus dynamics are not required and qualitative perfusion information is sufficient, the desired information could be extracted from hyperpolarized fumarate and pyruvate alone, acquired at higher fields with better spectral separation. Copyright © 2016 John Wiley & Sons, Ltd.     

Migraine and the hypothalamus

Migraine is a complex brain disorder where several neuronal pathways and neurotransmitters are involved in the pathophysiology. To search for a specific anatomical or physiological defect in migraine may be futile, but the hypothalamus, with its widespread connections with other parts of the central nervous system and its paramount control of the hypophysis and the autonomic nervous system, is a suspected locus in quo. Several lines of evidence support involvement of this small brain structure in migraine. However, whether it plays a major or minor role is unclear. The most convincing support for a pivotal role so far is the activation of the hypothalamus shown by positron emission tomography (PET) scanning during spontaneous migraine attacks. A well-known theory is that the joint effect of several triggers may cause temporary hypothalamic dysfunction, resulting in a migraine attack. If PET scanning had consistently confirmed hypothalamic activation prior to migraine headache, this hypothesis would have been supported. However, such evidence has not been provided, and the role of the hypothalamus in migraine remains puzzling. This review summarizes and discusses some of the clues.     

Delivering Child Community Psychology Services in the Community: Experiences from the NIPPERS Project

Background: The NIPPERS (Nursery Intervention Project for Parents & Education Related Services) was a novel community psychology service based in nursery settings in socio‐economically disadvantaged, inner‐city areas in London. Method: The service included consultation work with nursery staff, structured parenting groups and individual sessions for parents. Results: The delivery of the clinical service and research evaluation underwent several changes in the first phase of the project, in particular to ensure that the service was acceptable and accessible to families and staff. Although take‐up of community services was higher than in the local clinic‐based services, it was not taken up by some 40% of parents. Due to the allocation design, it was not possible to measure the effectiveness of the intervention. Conclusions: The NIPPERS service was successful in delivering a community child psychology service to families with high levels of early child behavioural problems at high risk for continuing difficulties.     

Efficacy of adjuvant chemotherapy in metastasizing cervix carcinoma. A pilot study

There are reported preliminary results of a pilot-study in the postoperative adjuvant treatment of cervical carcinoma with involvement of the iliac lymph nodes. It was done a prospective randomized study. There were 3 groups of treatment: adjuvant chemotherapy with a combination of Cisplatin and 5-Fluorouracil over 6 cycles; adjuvant chemotherapy like in the first group over 3 cycles plus Telecobalt-irradiation till the doses of 50 Gy in the small pelvis; and postoperative irradiation with Telecobalt till the doses of 50 Gy in the small pelvis. The fate of 41 patients could be evaluated. There were no statistical differences between the 3 groups in age, histology, staging and follow-up. Also the survival rate and the rate of the disease-free time didn't show a significant difference, but it seems, that the chemotherapy with Cisplatin and 5-Fluorouracil could be able to improve the poor prognosis of the cervical carcinoma with metastases.     

von Willebrand factor-collagen binding activity is increased in newborns and infants

ABSTRACT. von Willebrand factor (vWF) antigen (vWF:Ag) and vWF-collagen binding activity (vWF:CBA) were measured in plasma by parallel quantitative ELISAs in normal newborns and infants ( n =71). The medians for vWF:Ag (IUjml) and vWF:CBA (Ujml), respectively, were 1.46 and 1.91 for 2-7 day-old (n = 43), 1.22 and 1.40 for 2-4 week-old (n = 14), 1.22 and 1.15 for 2-6-month-old (n = 14) infants and 0.98 and 1.08 (n = 36) in normal adults. Elevated levels of vWF:Ag, but particularly vWF:CBA were seen for up to 4 weeks of life reaching adult levels between 2 and 6 months of life. The elevated levels of the vWF parameters indicate that caution should be exercised when interpreting laboratory data and diagnosing von Willebrand disease in newborns and young infants and warrant the use of age-specific reference ranges. The efficient haemostasis observed during early neonatal life may in part be due to the increased ability of vWF to interact with collagen.     

Selenium status of New Zealand infants fed either a selenium supplemented or a standard formula

Objective: New Zealand soils are deficient in the essential micronutrient, selenium. New Zealand infants have low selenium levels at birth and experience a further decline if fed cows milk based formula. This study examined the selenium status of infants fed with a new commercially available selenium supplemented formula.
Methodology Forty-four newborn infants, whose mothers wished to formula feed, were randomized in an open controlled trial to be fed a commercially available selenium supplemented cows milk formula (containing 17 μg Se/L) or an unsupplemented formula (containing 4.6 μg Se/L). Cord, 1 and 3 month blood samples were obtained for selenium status (plasma and red cell selenium and glutathione peroxidase) and thyroid function.
Results Mean plasma selenium and glutathione peroxidase values were significantly higher in supplemented than unsupplemented infants at 1 month (unpaired t -tests; P <0.0001 and P = 0.001 respectively) and 3 months ( P <0.0001 and P = 0.0005). Analysis within treatment groups between time points (paired t -tests) showed that selenium supplementation prevented the fall in plasma selenium from birth to 1 month seen in unsupplemented infants and was associated with a rise in levels between 1 and 3 months ( P = 0.002).
Conclusions Supplementing cows milk formula with selenium to replicate the levels found in breast milk is nutritionally sound. Feeding from a few days of age with a formula containing 17 μg Se/L in infants with low selenium status at birth is sufficient to cause a rise to 80% of adult levels at 3 months of age.     

Sudden hearing loss following infectious mononucleosis: possible effect of altered immunoregulation

Sudden, permanent hearing loss developed in three young patients. In an attempt to determine a viral etiology, their humoral and cell-mediated responses to a panel of seven viruses linked to deafness and altered immunity were measured. Although a specific viral cause was not determined, a mild Epstein-Barr virus infection was documented for each patient. It had preceded their hearing loss onset by 1 to 4 months. Evidence of altered cell-mediated responses to Epstein-Barr virus antigens was found in each patient. It is proposed that, in certain susceptible individuals, a temporary cellular immunosuppression, which accompanies normal recovery from Epstein-Barr virus infection, may provide an opportunity for a viral invasion of, or a latent viral reactivation in, the inner ear. This invasion or reactivation leads to deafness.