Blood-brain barrier and blood volume imaging of cerebral glioma using functional CT: A pictorial review

Five cases of cerebral glioma are presented here that illustrate the benefit of functional CT imaging of blood-brain barrier permeability and cerebral blood volume. Functional CT uses Patlak analysis of a single location dynamic sequence to extract physiological information that is useful clinically in the assessment of cerebral gliomas. Functional CT offers distinct advantages over other functional modalities including clearer delineation of tumour, tumour grading, measurement of tumour activity and monitoring response to therapy.     

The importance of the mesofascial interface in complete mesocolic excision

Complete mesocolic excision (CME) with Central Vascular Ligation (CVL) is progressively gaining acceptance as the most updated surgical treatment in the multimodal management of colonic cancer. The concept is based on excision of the affected organ with its related primitive dorsal mesenterium as an intact package to maximize local clearance, and high tie ligation to boost regional control, translating the original concept of Total Mesorectal Excision proposed by Heald for rectal cancer. Aim of this review is to analyze the modern concept of the mesenteric organ, with particular regard to the interfaces between its single components and the importance of the meso-fascial interface as the correct plane of separation.The integrity of the mesocolon excised along the meso-fascial interface (meso-fascial separation) prevents any breach of its surface and underlying structures, preserving the radial margin and the complex network of the meso-structure, avoiding any spillage of neoplastic cells within the surgical field. Central Vascular ligation allows for the most effective harvesting of lymph nodes, particularly of the apical ones, whose removal appears to be crucial in optimizing regional control.A surgical plane developed along the meso-fascial interface, coupled with high tie ligation, yields higher quality of surgical specimen, with better oncologic outcome in terms of local recurrence rate, disease-free and overall survival.     

Retrograde leptomeningeal venous approach for dural arteriovenous fistulas at foramen magnum

A 72-year-old man presented with sudden right homonymous hemianopsia. Work-up imaging revealed a left occipital haematoma and an arteriovenous fistula supplied by the meningeal branches to the clivus from the left vertebral artery (VA) with a rostral venous reflux into cortical veins. A microcatheter was advanced through brainstem veins into the venous collector. A compliant balloon was placed in the left VA facing the origin of feeders. The balloon was inflated to protect the vertebrobasilar circulation from embolic migration. Onyx was injected by the transvenous catheter. Control angiogram revealed exclusion of the lesion.Informed consent was obtained from the patient.     

Documentation of Psychiatric Disorders and Related Factors in a Large Sample Population of HIV-Positive Patients in California

This retrospective cohort study examined electronic medical records of HIV-positive patients in California (N = 7,834) to find the prevalence of any psychiatric condition and the associations between several factors and the likelihood of these disorders. Approximately 53 % of the patients in this study had a documented psychiatric condition, including 23 % who had a mood disorder, 19 % who had a substance-related disorder, and 16 % who had an anxiety disorder. After controlling for potential confounders, significant positive associations (p < 0.001) were found between female gender and the presence of any mood disorder (adjusted odds ratio [95 % confidence interval, 95 %CI] = 1.58 [1.26–1.99]) or anxiety disorder (AOR = 1.54 [1.18–2.02]) and between homosexual orientation and the presence of any psychiatric condition (AOR = 1.33 [1.15–1.55]), mood disorder (AOR = 1.71 [1.42–2.07]), or anxiety disorder (AOR = 1.41 [1.22–1.88]). There were also significant negative associations between African-American race and the presence of any psychiatric condition (AOR = 0.68 [0.60–0.77]), mood disorder (AOR = 0.74 [0.64–0.86]), anxiety disorder (AOR = 0.43 [0.36–0.52]), or substance-related disorder (AOR = 0.78 [0.67–0.91]) and between state/federal insurance and the presence of any psychiatric condition (AOR = 0.70 [0.62–0.79]), mood disorder (AOR = 0.71 [0.62–0.80]), or anxiety disorder (AOR = 0.77 [0.66–0.89]).     

The role of nuts in the optimal diet: Time for a critical appraisal?

During the last decades, nuts have attracted the attention of researchers for their potential benefits in cardiovascular prevention. We discuss here some aspects of the assumed beneficial effects of nuts, weighing them against potential harm. Epidemiological observations and controlled intervention trials consistently suggest that nuts consumption is associated with improved serum lipid profile, thus helping decrease cardiovascular risk. Being nuts an energy dense food, their impact on energy balance and body weight should be considered. In particular, the claim that adding nuts to the habitual diet, thus increasing calorie intake, does not cause body fat accumulation still needs evidence and biological plausibility. The potential risk associated with the relatively frequent occurrence of allergic reactions following the consumption of nuts is also discussed.     

A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency

Isolated mitochondrial complex IV (cytochrome c oxidase) deficiency is an important cause of mitochondrial disease in children and adults. It is genetically heterogeneous, given that both mtDNA-encoded and nuclear-encoded gene products contribute to structural components and assembly factors. Pathogenic variants within these proteins are associated with clinical variability ranging from isolated organ involvement to multisystem disease presentations. Defects in more than 10 complex IV assembly factors have been described including a recent Lebanese founder mutation in PET100 in patients presenting with Leigh syndrome. We report the clinical and molecular investigation of a patient with a fatal, neonatal-onset isolated complex IV deficiency associated with multiorgan involvement born to consanguineous, first-cousin British Asian parents. Exome sequencing revealed a homozygous truncating variant (c.142C>T, p.(Gln48*)) in the PET100 gene that results in a complete loss of enzyme activity and assembly of the holocomplex. Our report confirms PET100 mutation as an important cause of isolated complex IV deficiency outside of the Lebanese population, extending the phenotypic spectrum associated with abnormalities within this gene.     

Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures

Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion molecule 1, very late antigen 2 (VLA-2), and VLA- 5, and were positive for extracellular matrix components fibronectin, laminin, and collagen types 3 and 4. LTBMC from myeloma patients and normal donors spontaneously secreted interleukin-6 (IL-6). However, levels of IL-6 correlated with the stage of disease; highest levels of IL-6 were found in LTBMC from patients with active myeloma. To identify the origin of IL-6 production, LTBMC from MM patients and normal donors were cocultured with BM-derived myeloma cells and cells from myeloma cell lines. IL-6 was induced by plasma cell lines that adhered to LTBMC such as ARH-77 and RPMI-8226, but not by nonadhering cell lines U266 and FRAVEL. Myeloma cells strongly stimulated IL-6 secretion in cocultures with LTBMC adherent cells from normal donors and myeloma patients. When direct cellular contact between LTBMC and plasma cells was prevented by tissue-culture inserts, no IL-6 production was induced. This implies that intimate cell-cell contact is a prerequisite for IL-6 induction. Binding of purified myeloma cells to LTBMC adherent cells was partly inhibited by monoclonal antibodies against adhesion molecules VLA-4, CD44, and lymphocyte function-associated antigen 1 (LFA-1) present on the plasma cell. Antibodies against VLA-4, CD29, and LFA-1 also inhibited the induced IL-6 secretion in plasma cell-LTBMC cocultures. In situ hybridization studies performed before and after coculture with plasma cells indicated that LTBMC adherent cells produce the IL-6. These results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo. These results provide a new perspective on tumor growth in MM and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM.     

Sezary cell morphology induced in peripheral blood lymphocytes: re- evaluation

In this study we examined the effect of mitogens and epidermal cells in inducing a Sezary cell morphology in normal peripheral blood lymphocytes. Peripheral blood mononuclear cells from six healthy volunteers were stimulated with the mitogens phytohemaglutinin and concanavalin A, and also cocultivated with human epidermal cell cultures. Incubation times with mitogens and epidermal cells were four days and stimulation of the lymphocytes by mitogens was confirmed by standard 3H-thymidine uptake. Standard transmission electron microscopy showed that in the mitogen-driven system 20% to 60% (33 +/- 15%) and in the epidermal cell-driven system 5% to 15% (8 +/- 4%) of the lymphoid cells exhibited mild to moderate indentation of the nuclei with nuclear contour indices (NCI) of 4.6 to 6.5 but no Sezary cells were observed (cells with NCI greater than 6.5 and up to 19.2). In the mitogen- stimulated preparation 2% to 5% (3 +/- 1%) of the lymphoid cells showed nuclear multilobulation resembling the cells seen in adult T cell lymphoma/leukemia. Incubation of mononuclear cells for longer periods of up to 4 weeks with mitogens and exogenous IL-2 resulted in no further morphologic changes. Using an indirect immunogold technique at the electron microscopic level, the cells showing nuclear indentation or lobulation were shown to bear both T helper (CD4) and T suppressor (CD8) cell phenotypes in a similar ratio to the total numbers of T helper and T suppressor cells present. Mitogens and epidermal cells are thus not able to induce a morphologic change to Sezary cells in normal peripheral blood lymphocytes.     

Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.