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Utjecaj kontinuirane infuzije inzulina na lučenje endotelina-1 tijekom operacije aortokoronarnog premoštenja u bolesnika sa šećernom bolešću [Influence of continuous insulin infusion on endothelin-1 expression during coronary artery bypass grafting in diabetics]
Get PDFBackground: Endothelial dysfunction (ED) accelerates atherosclerosis in diabetics. ET-1 is one of the most potent vasoconstrictors and a marker of endothelial dysfunction (ED). Hyperglycemia and cardiopulmonary bypass (CPB) exacerbate ED which can be prevented by perioperative gycemic control.
Methods: Fourty-seven diabetics undergoing elective surgical myocardial revascularization were randomized to perioperative glycemic controll by bolus (BOL) or continuous insulin infusion (KII). Systemic and coronary blood samples were obtained at predefined time points. Insulin rates were applied according to protocols. ET-1 levels were determined by ELISA. During and after procedure hemodynamic parameters, myocardial damage markers and clinical outcomes were measured.
Results: Continuous insulin infusion (KII) significantly reduced ET-1 expression in systemic F(1,45)= 6,873; p=0,012, but not in coronary circulation BOL 5,00±1,22 vs KII 4,36±1,06; p=0,062. KII obtained better gycemic control in postoperative period (p=0,008) and reduced overall GUK during observed time period : F(1,45)=13,132; p=0,001. There were no differences in systemic inflammatory response, myocardial damage or clinical outcomes.
Conclusion: KII reduces ET-1 expression in diabetics undergoing myocardial revascularization with CPB in systemic but not coronary circulation. Effect is most likely due to better and more stable gycemia control and avoidance of hyperglycemia. Overall glycemic control was better in KII group with no effect on clinical outcomes
Single cell immune profiling by mass cytometry of newly diagnosed chronic phase chronic myeloid leukemia treated with nilotinib
Get PDFMonitoring of single cell signal transduction in leukemic cellular subsets has been proposed to provide deeper understanding of disease biology and prognosis, but has so far not been tested in a clinical trial of targeted therapy. We developed a complete mass cytometry analysis pipeline for characterization of intracellular signal transduction patterns in the major leukocyte subsets of chronic phase chronic myeloid leukemia. Changes in phosphorylated Bcr-Abl1 and the signaling pathways involved were readily identifiable in peripheral blood single cells already within three hours of the patient receiving oral nilotinib. The signal transduction profiles of healthy donors were clearly distinct from those of the patients at diagnosis. Furthermore, using principal component analysis, we could show that phosphorylated transcription factors STAT3 (Y705) and CREB (S133) within seven days reflected BCR-ABL1IS at three and six months. Analyses of peripheral blood cells longitudinally collected from patients in the ENEST1st clinical trial showed that single cell mass cytometry appears to be highly suitable for future investigations addressing tyrosine kinase inhibitor dosing and effect
Ultrasound and dynamic functional imaging in vascular cognitive impairment and Alzheimer's disease
Get PDFBACKGROUND:
The vascular contributions to neurodegeneration and neuroinflammation may be assessed by magnetic resonance imaging (MRI) and ultrasonography (US). This review summarises the methodology for these widely available, safe and relatively low cost tools and analyses recent work highlighting their potential utility as biomarkers for differentiating subtypes of cognitive impairment and dementia, tracking disease progression and evaluating response to treatment in various neurocognitive disorders. -----
METHODS:
At the 9th International Congress on Vascular Dementia (Ljubljana, Slovenia, October 2015) a writing group of experts was formed to review the evidence on the utility of US and arterial spin labelling (ASL) as neurophysiological markers of normal ageing, vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Original articles, systematic literature reviews, guidelines and expert opinions published until September 2016 were critically analysed to summarise existing evidence, indicate gaps in current knowledge and, when appropriate, suggest standards of use for the most widely used US and ASL applications. -----
RESULTS:
Cerebral hypoperfusion has been linked to cognitive decline either as a risk or an aggravating factor. Hypoperfusion as a consequence of microangiopathy, macroangiopathy or cardiac dysfunction can promote or accelerate neurodegeneration, blood-brain barrier disruption and neuroinflammation. US can evaluate the cerebrovascular tree for pathological structure and functional changes contributing to cerebral hypoperfusion. Microvascular pathology and hypoperfusion at the level of capillaries and small arterioles can also be assessed by ASL, an MRI signal. Despite increasing evidence supporting the utility of these methods in detection of microvascular pathology, cerebral hypoperfusion, neurovascular unit dysfunction and, most importantly, disease progression, incomplete standardisation and missing validated cut-off values limit their use in daily routine. -----
CONCLUSIONS:
US and ASL are promising tools with excellent temporal resolution, which will have a significant impact on our understanding of the vascular contributions to VCI and AD and may also be relevant for assessing future prevention and therapeutic strategies for these conditions. Our work provides recommendations regarding the use of non-invasive imaging techniques to investigate the functional consequences of vascular burden in dementia
Effect of preoperative topical diclofenac on intraocular interleukin-12 concentration and macular edema after cataract surgery in patients with diabetic retinopathy: a randomized controlled trial
Get PDFAIM:
To determine if preoperative treatment with a topical non-steroidal anti-inflammatory drug (NSAID) lowers the concentration of intraocular interleukin (IL)-12 and the incidence of postoperative macular edema in patients with non-proliferative diabetic retinopathy undergoing cataract surgery. -----
METHODS:
A total of 55 patients were randomized to diclofenac (n=27) or placebo (n=28). Patients receiving diclofenac started preoperative treatment with 0.1% topical diclofenac four times a day 7 days before cataract surgery and the therapy was discontinued 30 days after surgery. Patients in the control group were administered placebo 7 days preoperatively and a standard postoperative therapy with 0.1% topical dexamethasone four times a day for 30 days after surgery. All patients received postoperative antibiotic prophylaxis with tobramycin eye drops four times daily for 30 days. Seven days before the cataract surgery, on the day of surgery, and 1, 7, 30, and 90 days after surgery, central foveal thickness (CFT) was measured with optical coherence tomography (OCT) and the aqueous humor was sampled at the beginning of cataract surgery for the analysis of IL-12 concentration. Due to loss to follow-up and insufficient aqueous humor samples, the data of 3 patients treated with diclofenac and 8 patients receiving placebo were not analyzed. -----
RESULTS:
The aqueous humor IL-12 concentration was significantly lower in the diclofenac group than in the placebo group (t=-2.85, p=0.007). The diclofenac group had a significantly smaller increase in CFT after phacoemulsification (F=13.57, p<0.001). -----
CONCLUSION:
Patients preoperatively treated with diclofenac had significantly lower intraocular levels of IL-12 and a lower increase in CFT, which indicates that a combination of preoperative and postoperative treatment with a topical NSAID may lower the incidence of postoperative macular edema in patients with diabetic retinopathy
Rituximab with dose-adjusted EPOCH as first-line treatment in patients with highly aggressive diffuse large B-cell lymphoma and autologous stem cell transplantation in selected patients
Get PDFAIM:
To assess the benefit of rituximab with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-DA-EPOCH) regimen as a first-line treatment for patients with diffuse large B-cell lymphoma (DLBCL) presenting with unfavorable or aggressive features, and autologous stem cell transplantation (ASCT) as a part of the first-line treatment for selected DLBCL patients with additional aggressive features. -----
METHODS:
We retrospectively analyzed 75 newly diagnosed DLBCL patients with Ki-67+≥80% or International Prognostic Index ≥2 who were treated with R-DA-EPOCH between 2005 and 2015. Of 24 DLBCL patients with additional aggressive features (Ki-67+≥90% or age-adjusted IPI≥2) who were planned to receive consolidation with ASCT, 17 patients underwent the procedure. We determined the overall response rate (ORR), complete remission (CR), partial remission (PR), 5-year overall survival (OS), and progression free survival (PFS) in all DLBCL patients and specifically those planned to receive ASCT. -----
RESULTS:
All 75 patients included in the analysis started one or more cycles of therapy. The ORR, CR, and PR rates were 80%, 55%, and 25%, respectively. The response was non-evaluable in 10 of 75 patients due to treatment discontinuation. The OS and PFS rates for all 75 patients were 70% and 61%, respectively, and 80% and 79%, respectively, for 24 planned-to-receive-ASCT patients. Age (≤65 vs >65 years) had no prognostic impact on OS and PFS (P=0.994 and P=0.827, respectively). -----
CONCLUSION:
Our retrospective analysis of one of the largest DLBCL patient cohorts outside the US National Cancer Institute showed that R-DA-EPOCH is a very effective therapeutic option as a first-line treatment of DLBCL patients with unfavorable prognostic features irrespective of their age. ASCT provided additional benefit for DLBCL patients with additional aggressive features
Mjerenje stabilnosti acetabularne komponente totalne endoproteze kuka ovisno o veličini učinjenoga defekta dna acetabuluma na modelu svinjske zdjelice [Measurement of acetabular component stability in total hip arthroplasty in correlation to the size of acetabular medial wall defect in pig pelvis model]
Get PDFINTRODUCTION: Cotyloplasty is a technique that involves making a perforation of the
medial wall of a shallow acetabulum and then inserting an acetabular cup with the medial
aspect of it’s dome beyond the Kohler’s line. Although this method is in use since 1976., so
far no one has not defined how much cotyloplasty can be performed to remain acetabular
component stablity.
OBJECTIVES: Measurement acetabular component stability depending on the diameter of
cotyloplasty.
MATERIALS AND METHODS: On the 24 pigs pelvis models iatrogenic medial wall defect
in different diameters (10,20,25,30mm) is made following with acetabular component
placement (size 44). Acetabulum was loaded for determining to which diameter of
cotyloplasty acetabular component remains stable, or at which point the remaining medial
wall of the acetabulum can´t withstand the load and acetabular cup moves through the pelvis
for more than 2 mm or breaks through acetabulum.
RESULTS: In our study we found that in the average person (weighing 70 kg), we can make
acetabular defect that is between 25 and 30 mm if we use the acetabular component size 44.
If it is a person with higher body weight, up to 100 kg, this defect should not exceed the
diameter of 25 mm.
CONCLUSION: For the first time maximal diameter of cotyloplasty which ensures the
primary stability of acetabular component is determed. We confirmed our hypothesis that
THA will have sufficient stability to ensure secondary bone ingrowth around it, if amount of
cotyloplasty does not exceed half of the acetabular component diameter. This information will
help orthopedic surgeons in preoperative planning of total hip arthroplasty and postoperative
rehabilitation in patients with hip dysplasia
Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: new insights
Get PDFAIM:
To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157. -----
METHODS:
Medication [BPC 157, L-NAME, L-arginine (alone/combined), saline] was bath at the blood deprived colon segment. During reperfusion, medication was BPC 157 or saline. We recorded (USB microscope camera) vessel presentation through next 15 min of ischemic colitis (IC-rats) or reperfusion (removed ligations) (IC + RL-rats); oxidative stress as MDA (increased (IC- and IC + RL-rats)) and NO levels (decreased (IC-rats); increased (IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction (OB)] for 3 d (IC + OB-rats), then received BPC 157 bath. -----
RESULTS:
Commonly, in colon segment (25 mm, 2 ligations on left colic artery and vein, 3 arcade vessels within ligated segment), in IC-, IC + RL-, IC + OB-rats, BPC 157 (10 μg/kg) bath (1 mL/rat) increased vessel presentation, inside/outside arcade interconnections quickly reappeared, mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME (5 mg) and L-arginine (100 mg). MDA- and NO-levels were normal in BPC 157 treated IC-rats and IC + RL-rats. In addition, on day 10, BPC 157-treated IC + OB-rats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects; the treated colon segment was of normal diameter, and only small adhesions were present. -----
CONCLUSION:
BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system
Kisspeptin as a promising oocyte maturation trigger for in vitro fertilisation in humans
Get PDFThe aim of this review is to analyse the effectiveness of exogenous kisspeptin administration as a novel alternative of triggering oocyte maturation, instead of currently used triggers such as human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) agonist, in women undergoing in vitro fertilisation (IVF) treatment. Kisspeptin has been considered a master regulator of two modes of GnRH and hence gonadotropin secretion, pulses and surges. Administration of kisspeptin-10 and kisspeptin-54 induces the luteinising hormone (LH) surge required for egg maturation and ovulation in animal investigations and LH release during the preovulatory phase of the menstrual cycle and hypothalamic amenorrhoea in humans. Exogenous kisspeptin-54 has been successfully administered as a promising method of triggering oocyte maturation, following ovarian stimulation with gonadotropins and GnRH antagonists in women undergoing IVF, due to its efficacy considering achieved pregnancy rates compared to hCG and GnRH agonists. Also, its safety in patients at high risk of developing ovarian hyperstimulation syndrome is noteworthy. Nevertheless, further studies would be desirable to establish the optimal trigger of egg maturation and to improve the reproductive outcome for women undergoing IVF treatment
Brainstem nuclei changes in migraine detected by transcranial sonography
Get PDFThe aim of this study was to estimate the role of transcranial sonography in detecting basal ganglia changes as structural biomarkers in migraine. Transcranial sonography was performed on Aloka prosound α-10. Semiquantitative and planimetric methods were applied when basal ganglia changes were detected. Comparison between groups was performed by unpaired Student's t test and Spearman's correlation test. We analyzed 30 migraine patients and 30 age-/sex-matched controls. Substantia nigra hyperechogenicity was detected in 36.7% migraineurs and in 13.3% controls (t test, p = 0.036888). Hyperechogenic substantia nigra was found in 70% aura patients and in 20% patients without aura (p = 0.007384). Mean substantia nigra echogenic size of all migraine patients was 0.16 ± 0.07 and 0.12 ± 0.043 cm2 in controls (t test, p = 0.0011). Lentiform nucleus hyperechogenicity was seen in 50% migraine patients and 13.3% controls (t test, p = 0.002267). Mean lentiform nucleus echogenic size of all migrenous patients was 0.34 ± 0.08 cm2 and in controls 0.20 ± 0.008 cm2 (t test, p = 0.0021). Caudate nucleus hyperechogenicity was found in 26.7% migraine patients and in 6.6% controls (t test, p = 0.037667). Mean frontal horn width in migraine patients was 8.73 ± 1.76 mm and in controls 7.10 ± 1.71 (t test, p = 0.0006). Substantia nigra hyperechogenicity correlated with disease duration (rho = -0.35521, p = 0.05467) and third ventricle width (rho = -0.68221, p = 0.02976). No other differences between migraineurs and controls were found. Our study has revealed differences in transcranial findings between migraineurs and controls, but overall significance of those findings are still to be evaluated