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The role of p53 isoforms’ expression and p53 mutation status in renal cell cancer prognosis
Get PDFObjectives: To analyze p53 mutations and gene expression of p53, ∆40p53, and ∆133p53 isoforms in renal cell cancer (RCC) tissues and normal adjacent tissue (NAT) and to associate them to clinical features and outcome. -----
Patients and methods: Forty-one randomly selected patients, with primary, previously untreated RCC, with complete clinicopathohistological data were analyzed. NAT samples were available for 37 cases. Expression of p53, ∆40p53 and ∆133p53 was determined using RT-qPCR. A functional yeast-based assay was performed to analyze p53 mutations. -----
Results: More than half (56.1%) of patients harbored functional p53 mutations, and they were significantly younger than those with wild type (WT) p53 (P = 0.032). Expression of p53, ∆40p53, and ∆133p53 was upregulated in mutant (MT) p53 RCC compared to WT p53 RCC tissues. However, there was no difference in expression of these isoforms between MT p53 RCC tissues and NAT. Expression of ∆133p53 was significantly downregulated in WT p53 tissues compared to NAT (P = 0.006). Patients that harbored functional p53 mutation had better overall survival (hazard ratio 4.32, 95% confidence interval 1.46-18.82, P = 0.006). Multivariate analysis demonstrated that tumor stage and p53 mutation might be used as independent prognostic marker for overall survival in RCC patients. -----
Conclusions: Our findings support the specific events in the carcinogenesis of RCC. p53 isoforms can be differentially expressed depending on p53 mutational status
Kidney and uro-trauma: WSES-AAST guidelines
Get PDFRenal and urogenital injuries occur in approximately 10-20% of abdominal trauma in adults and children. Optimal management should take into consideration the anatomic injury, the hemodynamic status, and the associated injuries. The management of urogenital trauma aims to restore homeostasis and normal physiology especially in pediatric patients where non-operative management is considered the gold standard. As with all traumatic conditions, the management of urogenital trauma should be multidisciplinary including urologists, interventional radiologists, and trauma surgeons, as well as emergency and ICU physicians. The aim of this paper is to present the World Society of Emergency Surgery (WSES) and the American Association for the Surgery of Trauma (AAST) kidney and urogenital trauma management guidelines
Promjene razine izotipova specifičih imunoglobulina u atopičara i zdravih ispitanika prije i tijekom prirodne izloženosti peludu biljke Ambrosia elatior L.
Get PDFThe physiologic way of responding to allergens in healthy subjects is not fully
understood, nor the immunopathological mechanism in patients with allergies.
Despite the accepted theory of Th1-type immune response in healthy subjects that
should result in the formation of "blocking antibodies" and thus the absence of a
clinical symptoms of allergic disease, no such increase was observed during the
natural exposure of the Ambrosia elatior plant pollen. For one immunoglobulin class
(sIgG2) slight fall in serum levels was shown, which could, theoretically, play a role in
neutralizing the circulating allergen.
The characteristics of humoral immunity in people with allergic diseases during the
natural exposure of the pollen of the Ambrosia elatior plant is not only an increase in
sIgE levels but also increase in some other classes and subclasses, traditionaly
classified as Th1 immunoglobulin (A1, G3, G4).
The results of this study show that the natural exposure of allergic persons to the
environmental allergen has the similar effect on increase of sIgG4 in allergic persons
comparable to those in hyposensitisation. Therefore, the rise of IgG4 is probably not
by itself a mechanism that leads to clinical improvement in hyposenzitized patients.
That argument, together with the high level of allergen-specific serum sIgM levels
and also other imunoglobuline classes, dispute against the "theory of blocking
antibodies".
The results obtained could be used for further research in patients with allergy,
primarily the investigation of total barrier function, dynamics of immunoglobulin
classes and subclasses in other body specimens (nose and mucous membrane
biopsies), determination of blood allergen levels and determination of sIgE using this
quantitative method, possible differences in sIgM and other sIg levels in patients with
anaphyllaxis, potential therapeutic application of sIgG2 antibodies as well as
research in immune cells and their mediators. That way, a more complete insight
about immune events in healthy people and patients with allergies could be obtained
Ovisnost adolescenata o internetu [Internet addiction in adolescents]
Get PDFIntroduction: Internet addiction is a growing globally generational, biopsychosocial, health and a bioethical problem which is still hard to determine and to describe because it's new and uncharted territory so accordingly it falls into obsessive compulsive disorder.
Aim: the aim of the research is to question the frequency of internet addiction, to deepen the comprehension of the pathological Internet, questioning the quality of life and personality dimensions according to the „Great Five“ theory, and to conduct analysis to determine are there differences to the level and the type in addictions of Croatian adolescents, as well as Polish and Finnish ones;
Method: the pattern in this research was made up by adolescents from Croatia, Finland and Poland. The examinees were giving their answers in writing via anonymous questionnaire on their IT classes.
Conclusion: this research determined that a great number of interviewed adolescents, 86,4% of them, does not show signs of internet addiction and 12,8% of them show signs of moderate addiction. 0,8% of interviewed adolescents show signs of alarmingly serious internet addiction. Croatian adolescents statistically show a significantly bigger internet addiction (20,7%) compared to Polish adolescent (11.1%) and especially opposed to Finnish ones (5,4%)
High-risk HPV infection in Kosovar female population
Get PDFObjectives: Kosovo’s current health care system does not support organized
nationwide cervical cancer screening and human papillomavirus (HPV)
vaccination programs. To date, no reliable data are available on cervical
cancer incidence and mortality in Kosovo, or on high-risk HPV (hr-HPV)
prevalence and HPV type distribution. Our aim is to determinate the prevaccination
prevalence and distribution of hr-HPVs and to assesses the
associations between sociodemographic characteristics and increased risk of
HPV infection in women from Kosovo. -----
Methods: Detection of hr-HPV DNA was performed in cervical swabs of
women that underwent routine gynecological and cytological evaluation by
using a clinically validated Abbott RealTime High Risk HPV test, Roche Linear
Array HPV Genotyping Test, HPV52 type-specific real-time PCR and an inhouse
GP5+/GP6+/68 PCR. -----
Results: The crude overall prevalence of any of the hr-HPVs was estimated at
13.1% (26/199; 95% confidence interval (CI): 9.1–18.5%), with HPV16 being
the most common type (7/26; 26.9%), followed by HPV31 and HPV51, each
detected in 4/26 (15.4%) cervical specimens, HPV18, detected in 3/26 (11.5%) specimens, HPV52 and HPV66, each detected in 2/26 (7.7%) specimens, and
HPV33, HPV45, HPV56, and HPV58, each detected in a single (3.9%)
specimen. Women over 40 (OR = 0.36), older than 18 at sexual debut (odds
ratio (OR) = 0.28), those that had delivered at least one child (OR = 0.32), and
those that had a history of pregnancy termination (OR = 0.39) were at lower
risk for HPV infection. -----
Conclusion: Because more than 70% of cervical precancerous lesions could
have been prevented in Kosovo using nationwide HPV-based cervical cancer
screening and HPV vaccination, it is of outmost importance to implement both
programs in the national health care system as soon as possible
Učinci pentadekapeptida BPC 157 na posttraumatski osteoartritis koljena u štakora [Effects of pentadecapeptide BPC 157 on post-traumatic knee osteoarthritis in the rat]
Get PDFIntroduction. Osteoarthritis (OA) is the most common joint disease and among the most important causes of pain, disability and economic loss in all populations. A substantial fraction (12 %) of the overall burden of disease of OA arises secondary to joint trauma. With the best current care of significant joint injuries, the risk of post-traumatic OA (PTOA) ranges from about 20 % to more than 50 %. Considering that disease-modifying OA therapies are presently not available, and numerous positive effects of pentadecapeptide BPC 157 on healing of different injuries and tissues, the need for this investigation is imposed.
Materials and methods. Research was conducted on surgical model of knee PTOA in the rat (female Wistar albino rats weighing an average of 200 g and aged 8-10 weeks, kept in standard conditions) after MCL transection, medial meniscectomy and ACL transection of the right knee. Pentadecapeptide BPC 157 was administred in doses of 10 μg/kg or 10 ng/kg, dissolved in drinking water, perorally (0,16 μg/ml or 0,16 ng/ml, 12 ml/rat/day, dailly till sacrifice), and dissolved in saline solution, intraarticularly (20 μg/ml or 20 ng/ml, 0,1 ml/aplication, two weeks interval, first aplication immediately after surgery, last aplication two weeks before sacrifice). Control groups received pure drinking water or 0,1 ml of saline solution intraarticularly. Considering route of administration and administred dose, after surgery animals were distributed in 12 treated and 6 control groups (each group with 5 animals), randomly (cotreatment 4 weeks, cotreatment 8 weeks, post-treatment 8 weeks - treatment started after 4 weeks). Throughout whole duration of experiment, functional measurements (gait analysis, extensor postural thrust, assessment test for knee contracture) were conducted on day 1, 7, 14, 28, 42 and 56 after surgery. Sacrifice was conducted on day 28 for cotreatment 4 weeks, and on day 56 for cotreatment 8 weeks and post-treatment. Immediately after sacrifice radiological interpretation and macroscopical assessment were conducted, as well as preparing of samples for histological interpretation.
Results. Functional indicators in all control groups clearly indicated significant loss of function of operated leg immediately after surgery. As opposed to control groups, all cotreated groups showed substantially faster and more complete functional recovery. In post-treated groups contrary to control groups improvement of function was visible throughout time, however definitive values differed significantly from normal values. Macroscopical and histological, as well as radiological indicators in control groups showed clearly expressed signs of moderate PTOA after 4 weeks, and clearly expressed signs of heavily, advanced PTOA after 8 weeks. As opposed to control groups, all cotreated groups showed substantially better results. In post-treated groups in comparison with control groups differences were significantly lower. Effectiveness of pentadecapeptide BPC 157 is clearly visible at peroral and intraarticular administration, and at doses of 10 μg/kg and 10 ng/kg. Statistical analysis showed results statistically significant (P<0,05).
Conclusion. Pentadecapeptide BPC 157 administration have substantial effect on prevention of developement and progression of PTOA, and on regression of already developed PTOA on surgical model of knee PTOA in the rat, independently of admistration route and administred dose
Inhibitor aktivatora plazminogena 1 u procjeni dugoročnoga ishoda bolesnika s akutnim infarktom srca s elevacijom ST spojnice liječenih primarnom perkutanom koronarnom intervencijom [Prognostic value of plasminogen activator inhibitor 1 on long term outcome in patients with acute myocardial infarcton with ST elevation treated with primary percutaneous coronary intervention]
Get PDFPrognostic value of plasminogen activator inhibitor-1 (PAI-1) in patients with acute ST
elevation myocardial infarction (STEMI) treated with primary percutaneous coronary
intervention (PCI) was not studied extensively.
Patients treated for STEMI with primary PCI within Sestre milosrdnice University Hospital
Centre were included in the study. Beside routine treatment, two additional blood samples were
taken for PAI-1 activity analyses: first one on admission, second one 24 hours after admission.
PAI-1 activity was analysed using commercial test Berichrom PAI (Siemens, Marburg,
Germany).
A total of 87 patients aged 61,1±12,2 were included in the study, with 71,3% males. First
sample PAI-1 activity correlated with anthropometric parameters, while percental increment in
second sample negatively correlated with weight, body mass index and waist and hip
circumference. Difference between two measurements higher than 3,7 U/mL was significantly
more prevalent in females, patients with anterior myocardial infarction and affected left anterior
descending artery, acute heart failure, worse final TIMI flow, slow flow, use of
thrombaspiration, higher peak creatin-kinase level, and lower body weight.
Long-term outcome data was available for 84 patients. Rise in PAI-1 activity related to worse
short- and long-term survival, and higher occurrence of intermediate- and long-term composite
endpoint
Effect of antiepileptic drug comedication on lamotrigine concentrations
Get PDFAIM:
To estimate the effect size of concomitant antiepileptic therapy on the concentrations of lamotrigine, a drug often prescribed in combination with other antiepileptic drugs (AED), which can act as enzyme inducers or inhibitors. -----
METHODS:
A total of 304 patients with epilepsy, aged 18-70 years, were divided into a lamotrigine monotherapy group and groups receiving lamotrigine with AEDs that act as enzyme inducers, enzyme inhibitors, or both. We compared lamotrigine monotherapy serum concentrations with those where lamotrigine was administered with a metabolic inhibitor valproate, metabolic inducers carbamazepine, oxcarbazepine, phenobarbital, phenytoin, or topiramate, and both an inducer and an inhibitor. -----
RESULTS:
Comparison of trough lamotrigine monotherapy concentrations and lamotrigine polytherapy concentrations showed an almost similar median concentration in case of drug-inducers, and higher lamotrigine concentration in case of comedication with valproate as an inhibitor. A significant difference was confirmed after dose correction (P<0.001). Significant positive correlations of lamotrigine trough serum concentrations with valproate were observed before and after the dose correction (r=0.480, P<0.001 and r=0.561, P<0.001, respectively). Positive correlations between the dose-corrected lamotrigine trough concentration and carbamazepine (r=0.439; PP<0.001) or monohydroxy metabolite of oxcarbazepine (MHD) (r=0.675; PP<0.001) were also significant. -----
CONCLUSION:
Higher valproate levels resulted in higher inhibition potency and higher lamotrigine levels. Increased dose-corrected concentrations of inducers carbamazepine and MHD, after the process of induction was finished, did not lower lamotrigine concentrations. These findings can be of clinical significance for optimal AED dosing
Neinvazivna metoda za određivanje parametara matematičkoga modela plućne cirkulacije [Noninvasive method for parameter identification of the mathematical model of pulmonary circulation]
Get PDFWe propose a reliable noninvasive method for the parameter identification of the five-element
Windkessel model of pulmonary circulation. The model parameter identification procedure is
based on minimization of the root mean square error between the pulmonary artery root
pressure calculated from the Doppler velocity profiles and the pressure from the Windkessel
model during the same period. The output from the model contains the calculated pulmonary
artery input impedance and the model parameters: pulmonary vascular resistance, two
compliances, inertance, and characteristic impedance. The results show that the five-element
Windkessel model reconstructs the main features of the pulmonary artery input impedance
very well. The pulmonary vascular resistance, the systolic, diastolic and mean pulmonary
artery pressures are in good agreement with the values obtained invasively from the
catheterization. Mean pressures obtained by our method are in a better agreement with the
mean pressures from the catheterization than mean pressures calculated from Chemla
equation. Sensitivity analysis shows that the mean pulmonary pressure is insensitive to slight
overestimation/ underestimation of all input parameters, except for the right atrium pressure.
The proposed method can serve in clinical practice as a good substitute for catheterization