La protonterapia: indicaciones y perspectivas

Protons have considerable targeting advantages in the conduct of precise conformational radiotherapy, enabling dose escalation and a better protection of critical organs. Protons differs from photons and electrons used in classical radiotherapy due to their specific physical characteristics, Bragg peak and narrow lateral penumbra. Currently, treatment of ocular melanoma, chordoma and chondrosarcoma of the base of skull and paediatric tumours are widely accepted. Others clinical indications are still being evaluated (meningioma, etc.). Generalised isocentric application and proton intensity modulation can increase the clinical indications for its use. It is a technique which, despite its current expansion, appears “restricted” because of the scarcity of equipments due to its high cost.     

Efficacy and safety of ibandronate in the treatment of opioid-resistant bone pain associated with metastatic bone disease: a pilot study.

PURPOSE: Bone metastases are associated with severe and sometimes intractable pain, compromising patient quality of life (QOL). This open-label pilot study investigated the effects of short-term intensive treatment with intravenous (i.v.) ibandronate on opioid-resistant bone pain in patients with skeletal metastases. PATIENTS AND METHODS: Eighteen patients with advanced tumors and metastatic bone disease received nonstandard treatment with 4 mg of ibandronate administered i.v. (2-hour infusion) for 4 consecutive days (16-mg total dose). Baseline opioid analgesic use was equivalent to 400 mg/d of morphine. Patients were assessed for 6 weeks or until death. Changes from baseline were determined for bone pain, opioid consumption, patient functioning, QOL, performance status, and biochemical markers of calcium metabolism and bone turnover. Renal function was assessed by serum urea and creatinine measurement. RESULTS: Short-term, intensive ibandronate treatment significantly reduced bone pain scores within 7 days (P <.001). Pain reductions were sustained over the study period. Ibandronate significantly improved QOL, patient functioning, and performance status (P <.05). Mean values of the urinary cross-links pyridinoline and deoxypyridinoline tended to increase after day 21, returning close to baseline values by day 42. There was no correlation between the change in crosslinks values and the change in pain scores after ibandronate treatment. Ibandronate was well tolerated, with no evidence of renal toxicity. CONCLUSION: Nonstandard, intensive treatment with i.v. ibandronate seems to have a marked analgesic effect in patients with opioid-resistant bone pain from metastatic bone disease. Further investigation is warranted.     

Alteration of intracellular pH and activity of CA3-pyramidal cells in guinea pig hippocampal slices by inhibition of transmembrane acid extrusion

Transmembrane acid extruders, such as electroneutral operating Na(+)/H(+)-exchangers (NHE) and Na(+)-dependent Cl(-)/HCO(3)(-)-exchangers (NCHE) are essential for the maintenance and regulation of cell volume and intracellular pH (pH(i)). Both of them are hypothesised to be closely linked to the control of excitability. To get further information about the relation of neuronal pH(i) and activity of cortical neurones we investigated the effect of NHE- and/or NCHE-inhibition on (i) spontaneous action potentials and epileptiform burst-activity (induced by bicuculline-methiodide, caffeine or 4-aminopyridine) and (ii) on pH(i) of CA3-neurones. NHE-inhibition by amiloride (0.25-0.5 mM) or its more potent derivative dimethylamiloride (50 microM) and NCHE-inhibition by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 0.25-0.5 mM) induced a biphasic alteration of neuronal activity: an initial, up to 30 min lasting, increase in frequency of action potentials and bursts preceded a growing and partially reversible suppression of neuronal activity. In BCECF-loaded neurones the pH(i), however, continuously decreased during either amiloride- or DIDS-treatment and reached its steady-state (DeltapH(i) up to 0.3 pH-units) when the neuronal activity was markedly suppressed. Combined treatment with amiloride (0.5 mM) and DIDS (0.5 mM) or treatment with harmaline alone (0.25-0.5 mM), which also continuously acidified neurones via inhibition of an amiloride-insensitive NHE-subtype, induced a monophasic and partially reversible suppression of neuronal activity. As an initial excitatory period failed to occur during combined NHE/NCHE-inhibition we speculate that its occurrence during amiloride- or DIDS-treatment resulted rather from disturbances in volume- than in pH(i)-regulation. The powerful inhibitory and anticonvulsive properties of NHE- and NCHE-inhibitors, however, very likely based upon intracellular acidification - as derived from our previous findings that a moderate increase in intracellular free protons is sufficient to reduce membrane excitability of CA3-neurones.     

Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation

OBJECTIVE: To assess the effects of high frequency stimulation of the subthalamic nucleus (STN) on axial symptoms occurring in advanced stages of Parkinson's disease (PD). METHODS: The efficacy of STN stimulation on total motor disability score (unified Parkinson's disease rating scale (UPDRS) part III) were evaluated in 10 patients with severe Parkinson's disease. The subscores were then studied separately for limb akinesia, rigidity, and tremor, which are known to respond to levodopa, and axial signs, including speech, neck rigidity, rising from a chair, posture, gait, and postural stability, which are known to respond less well to levodopa. Patients were clinically assessed in the "off" and "on" drug condition during a levodopa challenge test performed before surgical implantation of stimulation electrodes and repeated 6 months after surgery under continuous STN stimulation. A complementary score for axial symptoms from the "activities of daily living" (ADL)-that is, speech, swallowing, turning in bed, falling, walking, and freezing-was obtained from each patient's questionnaire (UPDRS, part II). RESULTS: Improvements in total motor disability score (62%), limb signs (62%), and axial signs (72%) obtained with STN stimulation were statistically comparable with those obtained with levodopa during the preoperative challenge (68%, 69%, and 59%, respectively). When levodopa and STN stimulation were combined there was a further improvement in total motor disability (80%) compared with preoperative levodopa administration. This consisted largely of an additional improvement in axial signs (84%) mainly for posture and postural stability, no further improvement in levodopa responsive signs being found. Axial symptoms from the ADL showed similar additional improvement when levodopa and STN stimulation were combined. CONCLUSION: These findings suggest that bilateral STN stimulation improves most axial features of Parkinson's disease and that a synergistic effect can be obtained when stimulation is used in conjunction with levodopa treatment.     

Quaking and miR-155 interactions in inflammation and leukemogenesis

Quaking (QKI) is a tumor-suppressor gene encoding a conserved RNA-binding protein, whose expression is downregulated in several solid tumors. Here we report that QKI plays an important role in the immune response and suppression of leukemogenesis. We show that the expression of Qki is reduced in lipopolysaccharide (LPS)-challenged macrophages, suggesting that Qki is a key regulator of LPS signaling pathway. Furthermore, LPS-induced downregulation of Qki expression is miR-155-dependent. Qki overexpression impairs LPS-induced phosphorylation of JNK and particularly p38 MAPKs, in addition to increasing the production of anti-inflammatory cytokine IL-10. In contrast, Qki ablation decreases Fas expression and the rate of Caspase3/7 activity, while increasing the levels of IL-1α, IL-1β and IL-6, and p38 phosphorylation. Similarly, the p38 pathway is also a target of QKI activity in chronic lymphocytic leukemia (CLL)-derived MEC2 cells. Finally, B-CLL patients show lower levels of QKI expression compared with B cells from healthy donor, and Qki is similarily downregulated with the progression of leukemia in Eμ-miR-155 transgenic mice. Altogether, these data implicate QKI in the pathophysiology of inflammation and oncogenesis where miR-155 is involved.     

Anatomical basis of laparoscopic medial‐to‐lateral mobilization of the descending colon

In laparoscopic colorectal resection, the medial‐to‐lateral approach has been largely adopted. This approach can be initiated by the division of either the inferior mesenteric artery (IMA) or the inferior mesenteric vein (IMV). This cadaveric study aimed to establish the feasibility of IMV dissection as the initial landmark of medial‐to‐lateral left colonic mobilization for evaluating the size of the peritoneal window between the IMV at the lower part of the pancreas and the origin of the IMA (IMA‐IMV distance) and the point of origin of the IMA compared to the lower edge of the third part of the duodenum (IMA‐D3 distance). These distances were recorded on 30 fresh cadavers. The IMA‐D3 distance was 0.4 ± 2.2 cm (mean ± SD). The IMA originated from the aorta at the level of or below the D3 in 21 cases (70%). The IMA‐IMV distance was 5.5 ± 1.8 cm and was greater or equal to 5 cm (large window) in 21 cases (70%). IMA‐IMV distance was correlated with IMA‐D3 showing that a large window was inversely correlated with a low IMA origin (P < 0.001). IMA‐D3 distance was not correlated with weight, height and sex. IMA‐IMV distance was largerin male (6.7 ± 0.9 vs. 4.9 ± 1.8, P = 0.001) and correlated with weight, (r = 0.60, 95%CI = 0.03–0.10, P < 0.001) and height (r = 0.54, 95%CI = 0.05–0.21, P = 0.002). IMV can be used as the initial landmark for laparoscopic medial‐to‐lateral dissection in two‐thirds of cases. A too‐small window can require first IMA division. The choice between the two different medial‐to‐lateral approaches could be made by evaluating the anatomical relationship between IMA, IMV, and D3. Clin. Anat., 2013. © 2013 Wiley Periodicals, Inc.     

The influence of oral health on patients' food perception: a systematic review

Oral food perception depends on somatosensory information that includes taste and can be modified by oral components and/or functions such as mastication. The purpose of this study was to describe the interplay between oral health, mastication and taste. A review according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses checklist was conducted on 615 publications found by both PubMed and backward research. Thirty‐one studies have been included. The results showed that the decline in taste ability observed during the healthy ageing process could be potentiated by the deterioration of oral health and poor oral hygiene. Prosthetic treatment could modify taste ability and oral food perception. A palatal covering with removable dentures can have an impact on taste perception which may depend on taste modality. During the mastication sequence, taste is apparently scattered throughout the oral cavity, probably through saliva. The deterioration of masticatory function modifies taste perception. Oral health and oral care should consider factors influencing patients' food perception and relations between taste and mastication. Therefore, dentists may modulate these factors to improve food perception and patients' eating pleasure and quality of life.