The effective dose (Deff) for electron beams.

BACKGROUND AND PURPOSE: Calculation of the effective dose and proposal of a dose specification method for the electron beams. PATIENTS AND METHODS: In a homogenous water phantom the 3D dose distributions for electron beams of energy 6, 9, 12, 15, 18 and 21 MeV and beam size 10x10 cm were calculated. For a volume encompassed with 80, 85 and 90% isodose, the mean dose and the SD were calculated for each energy. Using the Brahme's formulae, the effective dose was calculated. RESULTS: The larger the minimum dose (value of the encompassing isodose), the larger the mean dose and the smaller the SD. The mean doses and SD to the volume encompassed with 80, 85 and 90% are in the range of 91-94%, and 5.1-6.2%, 93-96% and 4.2-4.6%, 94-96% and 3.0-3.2%, respectively. Thus the effective dose for the volume encompassed with 80, 85 and 90% are about 90, 93 and 95%, respectively. CONCLUSION: Taking into account the requirements regarding dose uniformity within the PTV and the sparing effect for normal tissue situated under the PTV, we propose to keep the 85% isodose as a minimum one and to prescribe the dose to the 90% isodose. The present method may be applied for single electron beams and typical cases.     

Reducing delirium and cognitive dysfunction after off-pump coronary bypass: A randomized trial

BackgroundNeuropsychiatric complications of surgical coronary revascularization are inconspicuous but frequent and clinically relevant. So far, attempts to reduce their occurrence, such as the introduction of off-pump coronary artery bypass (OPCAB) grafting method, have not brought the desired results. The aim of this trial was to determine whether using any of the 2 selected modifications of OPCAB could decrease the incidence of these undesired sequelae.MethodsIn this single-center, assessor- and patient-blinded, superiority, randomized controlled trial, 192 patients scheduled for elective isolated OPCAB were randomized to 3 parallel arms. The control arm underwent “conventional” OPCAB with vein grafts. The first study arm underwent anaortic OPCAB (ANA) with total arterial revascularization. The second study arm underwent OPCAB with vein grafts using carbon dioxide surgical field flooding (CO₂FF). Outcomes included the incidence of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD).ResultsThe incidence of PD was 35.9% in the control (OPCAB) arm, 32.8% in the CO₂FF arm, and 12.5% in the ANA arm (χ² [2, N = 191] = 10.17; P = .006). Post hoc tests revealed that the incidence of PD in the ANA arm differed from that in the OPCAB arm (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.68; P = .002). The incidence of ePOCD was 34.4% in the OPCAB arm, 28.1% in the CO₂FF arm, and 9.5% in the ANA arm (χ² [2, N = 191] = 11.58; P = .003). Post hoc tests revealed that the incidence of ePOCD differed between the ANA and OPCAB arms (OR, 0.20; 95% CI, 0.06-0.58; P < .001).ConclusionsPerforming ANA significantly decreases the incidence of PD and ePOCD compared with “conventional” OPCAB with vein grafts, whereas CO₂FF is inconsequential in this regard. These results, which probably reflect decreased delivery of embolic load to the brain in ANA, may have practical applicability in daily practice to improve clinical outcomes.     

Melatonin nephroprotective action in Zucker diabetic fatty rats involves its inhibitory effect on NADPH oxidase

Excessive activity of NADPH oxidase (Nox) is considered to be of importance for the progress of diabetic nephropathy. The aim of the study was to elucidate the effect of melatonin, known for its nephroprotective properties, on Nox activity under diabetic conditions. The experiments were performed on three groups of animals: (i) untreated lean (?/+) Zucker diabetic fatty (ZDF) rats; (ii) untreated obese diabetic (fa/fa) ZDF rats; and (iii) ZDF fa/fa rats treated with melatonin (20 mg/L) in drinking water. Urinary albumin excretion was measured weekly. After 4 wk of the treatment, the following parameters were determined in kidney cortex: Nox activity, expression of subunits of the enzyme, their phosphorylation and subcellular distribution. Histological studies were also performed. Compared to ?/+ controls, ZDF fa/fa rats exhibited increased renal Nox activity, augmented expression of Nox4 and p47^phox subunits, elevated level of p47^phox phosphorylation, and enlarged phospho‐p47^phox and p67^phox content in membrane. Melatonin administration to ZDF fa/fa rats resulted in the improvement of renal functions, as manifested by considerable attenuation of albuminuria and some amelioration of structural abnormalities. The treatment turned out to nearly normalize Nox activity, which was accompanied by considerably lowered expression and diminished membrane distribution of regulatory subunits, that is, phospho‐p47^phox and p67^phox. Thus, it is concluded that: (i) melatonin beneficial action against diabetic nephropathy involves attenuation of the excessive activity of Nox; and (ii) the mechanism of melatonin inhibitory effect on Nox is based on the mitigation of expression and membrane translocation of its regulatory subunits.     

20-MHz Ultrasound for Measurements of Flow-Mediated Dilation and Shear Rate in the Radial Artery

A high-frequency scanning system consisting of a 20-MHz linear array transducer combined with a 20-MHz pulsed Doppler probe was introduced to evaluate the degree of radial artery flow-mediated dilation (FMD [%]) in two groups of patients after 5?min of controlled forearm ischemia followed by reactive hyperemia. In group I, comprising 27 healthy volunteers, FMD (mean?±?standard deviation) was 15.26?±?4.90% (95% confidence interval [CI]: 13.32%–17.20%); in group II, comprising 17 patients with chronic coronary artery disease, FMD was significantly less at 4.53?±?4.11% (95% CI: 2.42%–6.64%). Specifically, the ratio FMD/SR (mean?±?standard deviation), was equal to 5.36?×?10^?4?±?4.64?×?10^?4 (95% CI: 3.54?×?10^?4 to 7.18?×?10^?4) in group I and 1.38?×?10^?4?±?0.89?×?10^?4 (95% CI: 0.70?×?10^?4 to 2.06?×?10^?4) in group II. Statistically significant differences between the two groups were confirmed by a Wilcoxon–Mann–Whitney test for both FMD and FMD/SR (p?<0.01). Areas under receiver operating characteristic curves for FMD and FMD/SR were greater than 0.9. The results confirm the usefulness of the proposed measurements of radial artery FMD and SR in differentiation of normal patients from those with chronic coronary artery disease.     

Clinical value of monoclonal antibodies and tyrosine kinase inhibitors in the treatment of head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of malignant tumours that affects over 500,000 patients per year. Treatment failure is generally due to the heterogeneity of these tumours and to the serious adverse effects associated with treatment. Immunological system impairment, which is common in HNSCC, further contributes to treatment failure by mediating tumour escape mechanisms. To date, the only clinically approved targeted therapy agent is cetuximab, a monoclonal antibody (mAb) that binds to, and inhibits, epidermal growth factor receptor, which is widely overexpressed in HNSCC. Cetuximab has been proven to induce antibody-dependent cellular cytotoxicity, further magnifying its therapeutic effect. DNA sequencing of HNSCC cells has identified the presence of mutated genes, thus making their protein products potential targets for therapeutic inhibition. Immune mechanisms have been found to have a significant impact on carcinogenesis, thus providing the rationale to support efforts to identify anticancer compounds with immunomodulatory properties. In the context of the rapid development of novel targeted agents, the aim of the present paper is to review our current understanding of HNSCC and to review the novel anticancer agents (mAbs and TKIs) introduced in recent years, including an assessment of their efficacy and mechanisms of action.     

Tapentadol – A representative of a new class of MOR-NRI analgesics

Tapentadol is a centrally acting analgesic with a dual mode of action as a μ-opioid receptor (MOR) agonist and a noradrenaline reuptake inhibitor (NRI). It was initially approved by the US Food and Drug Administration in November 2008 for the treatment of moderate-to-severe acute pain in adult patients, and in August 2011, for chronic pain in an prolonged release form in the same population. Due to its limited protein binding capacity, the absence of active metabolites and significant microsomal enzyme induction or inhibition, tapentadol has a limited potential for drug–drug interactions. It appears to be well-tolerated and effective in the treatment of moderate-to severe acute and chronic pain. Owing to its dual mechanism of action, it is hypothesized to be good option in the treatment of both nociceptive and neuropathic pain.     

Orexins Protect Neuronal Cell Cultures Against Hypoxic Stress: an Involvement of Akt Signaling

Orexins A and B are peptides produced mainly by hypothalamic neurons that project to numerous brain structures. We have previously demonstrated that rat cortical neurons express both types of orexin receptors, and their activation by orexins initiates different intracellular signals. The present study aimed to determine the effect of orexins on the Akt kinase activation in the rat neuronal cultures and the significance of that response in neurons subjected to hypoxic stress. We report the first evidence that orexins A and B stimulated Akt in cortical neurons in a concentration- and time-dependent manner. Orexin B more potently than orexin A increased Akt phosphorylation, but the maximal effect of both peptides on the kinase activation was very similar. Next, cultured cortical neurons were challenged with cobalt chloride, an inducer of reactive oxygen species and hypoxia-mediated signaling pathways. Under conditions of chemical hypoxia, orexins potently increased neuronal viability and protected cortical neurons against oxidative stress. Our results also indicate that Akt kinase plays an important role in the pro-survival effects of orexins in neurons, which implies a possible mechanism of the orexin-induced neuroprotection.     

Functional Capacity of Patients in the Early Period After the Embolization of Cerebrovascular Malformations: Preliminary Findings

ABSTRACT: Research into outcomes of endovascular intervention for cerebral blood vessel malformations has previously focused on the clinical picture of the disease, death rate, comparison of surgical methods, and the most common postoperative and postbleeding complications. From the nursing standpoint, the crucial elements in assessing postoperative patients are functional outcome defining patients' ability to function in life and recognition of impairments in which patients will be dependent on the nursing staff. The aim of the study was to assess functional capacity of patients before and after the embolization of cerebral blood vessel malformations in the aspect of nursing care. The study included 38 patients after embolization of cerebral blood vessels. The assessment of their condition using the Functional Capacity Scale was performed twice: before and after the surgical procedure. The research shows that on the day of admission to hospital, patients had greatest difficulty performing hygienic activities (p < .0001), satisfying physiological needs (p < .0001), and consuming their meals (p < .004). Headache (p < .002) and poor psychological state (p < .0001) manifesting itself through mild depression constituted other serious problems. After the surgery, vast majority of patients were independent in terms of self-care (p ≤ .03). Headache occurred in the case of 21% of patients, and psychological state improved in 34% of patients, which shows that there is a major demand for care in this sphere.     

Dynamic changes in specific anti-L-asparaginase antibodies generation during acute lymphoblastic leukemia treatment

Background

L-asparaginase (L-asp) remains one of the key components of acute lymphoblastic leukemia therapy. Immune reactions to the drug are associated with its diminished activity. The aim of the study was to determine the level of IgM, IgG and IgE-class anti-L-asp antibodies during the induction and reinduction phases of acute lymphoblastic leukemia therapy and their influence on L-asp activity.