MODIFIED TREATMENT OF HEPATORENAL SYNDROME TYPE I DEPENDING ON THE STAGE OF ACUTE KIDNEY INJURY.

Hepatorenal syndrome is a severe complication of liver cirrhosis which is difficult to treat because of a very fast course and lack of adequate dosing recommendations due to the stage of the disease. In this study we aimed to refine the treatment of hepatorenal syndrome type I by modifying the dose of terlipressin, depending on the stage of acute kidney injury (AKI). Objective - to improve the treatment method of hepatorenal syndrome type I in patients with alcoholic liver cirrhosis by selecting the dose of terlipressin depending on the stage of acute kidney injury. For this study were enrolled 161 patients with diagnosis alcoholic liver cirrhosis, complicated with the hepatorenal syndrome. All patients were were randomly divided into control (group 1) (n=79) and study (group 2) (n=82) groups depending on the treatment received (terlipressin in the standard dosage or modified by the response-guided titration method). If the serum creatinine level decreased less than 25% from the baseline, the dose of terlipressin was gradually increased but did not accede 12 mg/24 hours. The stage of AKI was diagnosed using the criteria of Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury, 2012. The risk of short term mortality (within the first 29 days) was prognosed by Model for End-Stage Liver Disease (MELD) score. The kidney function improved better in persons with a modified dose of terlipressin: the complete response rate in them was 81.7%. The response rate in those who received the standard treatment, was 66.7% only (p˂0.05). It was found that the effective dosage of terlipressin is 3 mg/24 for AKI stage I; 6 mg/24 - for AKI stage II; 12 mg/24 - for AKI stage III. The relapse of the disease occurred only in 23.2% patients with modified treatment against 40.1% in the control group (p˂0.05). Short term survival was also significantly higher in the study group - 54.9%, while in the control group it was 37% only (p˂0.05). Thus, correction of terlipressin dosage could improve the results of the treatment and reduce mortality in patients with hepatorenal syndrome type I.

Primary cardiac tumours: how well can prenatal diagnosis "predict" postnatal outcome?

OBJECTIVE: Primary foetal cardiac tumours are rare congenital malformations. They can cause a flow obstruction, arrhythmias and can lead to cardiac failure, hydrops or death. Postnatal management is based on patient´s clinical and hemodynamic impairment. METHODS: We retrospectively reviewed data from 2009-2019 from our gynaecology clinic and also data regarding postnatal follow-up from our partner paediatric institution. RESULTS: In this period, we diagnosed six cases with foetal cardiac tumours. In four cases, multiple rhabdomyomas were present. Three patients did not have serious complications pre- or postnatally. In one case, tumours were obliterating both the inflow and the outflow of the left ventricle. The child died at three months of age. Tuberous sclerosis was confirmed in all the cases with rhabdomyomas. One child had a fibroma filling the left ventricle. Despite an uneventful prenatal period, the patient got postnatally symptomatic. Tumour was considered inoperable and the child died at the age of five months. In one case a single right ventricular unspecified tumour was diagnosed, without any complications. CONCLUSION: Prognosis closely depends on early diagnosis, clinical manifestations and the possibility of surgical tumour removal if necessary. In confirmed rhabdomyomas, tests for tuberous sclerosis are mandatory (Tab. 1, Fig. 2, Ref. 18). Text in PDF www.elis.sk Keywords: rhabdomyoma, fibroma, prenatal diagnosis, ultrasound, tuberous sclerosis.

Evaluation of protein expression and DNA methylation profiles detected by pyrosequencing in invasive breast cancer.

Breast carcinoma is the most common cancer with high mortality caused by metastatic disease. New molecular biomarkers predicting the tumour's metastatic potential would therefore improve metastasis prevention and personalised care. The aim of the study was to investigate the relationship between DNA methylation levels in invasivity and metastasising associated genes with aberrant protein expression and also to evaluate whether a similar DNA methylation level is present in the tumour and circulating cell-free DNA for utilising plasma DNA methylation as prognostic biomarker. By using pyrosequencing, we analysed DNA methylation levels of 11 genes, namely APC, ADAM23, CXCL12, ESR1, PGR B, CDH1, RASSF1A, SYK, TIMP3, BRMS1 and SOCS1 in tumour, plasma and peripheral blood cells from 34 patients with primary breast cancer, as well as plasma and peripheral blood cells from 50 healthy controls. Simultaneously, the expression of related proteins in paraffin-embedded tumour samples was evaluated by immunohistochemistry. Statistical analysis was performed by SPSS statistics 15.0 software. Tumour DNA hypermethylation was found in most commonly methylated RASSF1A (71.9%), APC (55.9%), ADAM23 (38%) and CXCL12 (34.4%) genes with methylation levels up to 86, 86, 53 and 64 %, respectively. In tumours, significantly higher methylation levels were found in nine genes, compared with the patients´ peripheral blood cell DNA. Furthermore, in patients methylation levels in peripheral blood cell DNA were significantly higher than in controls in CXCL12, ESR1 and TIMP3 genes, but the values did not exceed 15%. On the other hand, no correlations were observed in patients between DNA methylation in tumours and cell-free plasma DNA. Moreover, in patients and controls nearly identical values of cumulative DNA methylation (43.6 % ± 20.1 vs. 43.7 % ± 15.0) were observed in plasma samples. A variable spectrum from high to none expressions presented in tumour tissues in all of the proteins evaluated, however in APC and CXCL12 genes a visible decreasing trend of mean DNA methylation level with increasing expression of the corresponding protein was observed. The DNA methylation profiles manifested in our group of breast carcinomas are cancer specific, but they are not the only cause that affects the silencing of evaluated genes and the decrease of relevant protein products. The clinical utility of DNA methylation testing in peripheral blood cell DNA for cancer diagnosis and therapy need to be further investigated.

Myocardial infarction paraneoplastically facilitated?

The prothrombotic effect of malignant diseases on organism is commonly known. We review the documentation of the Medical Department in Liptovsky Mikulas filed in years 1996-2002 (15,512 patients). 120 patients suffered from significantly coinciding acute myocardial infarction and malignant diseases (p = 0.05). In 17 of them the correlation was possible; in 38 it was probable. Most common were the tumours of digestive organs, uropoetic system and oncohematological diseases. The acute myocardial infarction usually preceded the diagnosis of malignant diseases. Under certain conditions, e.g. under that of paraneoplastic syndrome, some acute myocardial infarctions can serve as a hint that it is necessary to assume and solve also possible presence of occult malignancies (Fig. 1, Re of 46).

["Nested" PCR for human papillomavirus detection and typing in samples from cervical lesions of gynecological patients]. / "Nested" PCR a jej vyuzitie pri detekcii a typizácii papilomavírusovej infekcie vo vzorkách z cervikálnych lézií gynekologických pacientok.

OBJECTIVE: The authors tested PCR--so called nested (N-PCR) for the detection of HPV in cervical lesions of uterus. This method is based on repeated amplification of specific viral DNA fragments. The sensitivity of N-PCR was compared to the sensitivity of the hybridization method. In the second part of the experiment positive samples underwent HPV typing by PCR. BACKGROUND: The effectiveness of N-PCR for HPV detection was verified on 30 samples from cytologically/histologically suspected cervical lesions. In these cases, previous detection by hybridization method was unsuccessful. The second group consisted of 21 samples acquired by conisation, in which HPV presence was confirmed by hybridization method. Post surgery HPV detection using hybridization technique was negative in this group of patients. RESULTS: By means of N-PCR the presence of HPV DNA was confirmed in all 30 samples from the first group (100%) and in 8 (38%) cases from the group of samples obtained after conisation. Type-specific PCR detection indicated HPV type 16 in 20 cases, HPV type 18 in 6 cases (from the first series). In the remaining 4 cases typing for HPV 16, 18, 31 and 33 was negative. In the second series all 8 samples were HR-HPV type 16. CONCLUSION: At the present time, N-PCR is probably the most sensitive HPV detection method. The only real disadvantages of the given technique are relatively high costs of diagnostics equipment and the requirement of highly qualified personel.

[Exchange amnioinfusion in conceptus with laparoschisis (first experience)]. / Výmenná amnioinfúzia u plodov s laparoschízou (Prvé skúsenosti).

OBJECTIVE: During amnioinfusion exchange (AE) a certain amount of amniotic fluid is repeatedly extracted and the same amount of physiological solution is consequently instilled into the amniotic fetal cavity. The aim of this procedure is to dilute the amniotic fluid that surrounds the eviscerated organs of fetuses with laparoschisis so as to avoid the genesis of fibrous coating on these organs. DESIGN: Prospective study. SETTING: Gynekologicko-pôrodnícka klinika SZU, FNsP akad. L. Dérera, Bratislava, Slovakia. METHODS: We have executed AE in five fetuses with laparoschisis since June 2002. Two patients underwent the treatment 2 times during the 32nd and 36th weeks of gestation. Two other patients were treated once during the 32nd week and one patient once during the 36th week. Under ultrasound control we used a spinal needle to extract 120-180 ml of dense, cloudy amniotic fluid. Consequently, we instilled the same amount of physiological solution warmed up to the temperature of 37 degrees C into the amniotic cavity through antibacterial filter. The fetuses were monitored cardiotocographically and with the help of ultrasound flowmetry in umbilical vessels, before and after the treatment. RESULTS: The AE were successful and without complications in all five cases. All patients delivered via elective caesarean section during the 36th - 37th gestation week. One patient delivered 24 hours after second AE due to the danger of intrauterine fetal hypoxia that was verified cardiotocographically. The other patients delivered 1-4 weeks after AE. CONCLUSION: The significance of AE lies primarily in the reduction of the occurrence of fibrous coating on eviscerated organs. It enables postnatal primary surgical closure of the defect in the front abdominal wall, an earlier onset of intestine peristalsis, transition from parenteral to peroral nutrition and shorter hospitalization.

[The little known Fay syndrome (benign carotidynia)]. / Málo známy Fayov syndróm (benígna karotidynia).

The authors describe the little known Fay syndrome (benign carotidynia, extracranial vascular cephalea). They emphasize the importance of a careful case-history (in particular sore throat--usually unilateral), with careful physical examination (palpation sensitivity of the carotid artery beneath the bifurcation). The authors assume that the syndrome is not as rare but that it is rarely correctly diagnosed. The drug of choice are non-steroid antirheumatic drugs. The authors describe in an epicritical manner eight of their own observations made during the last three years.

[A rheumatologic syndrome (paraneoplastic?) in benign tumors]. / Reumatoidný syndróm ("paraneoplastický"?) pri benígnych nádoroch.

The authors discuss the possible development of rheumatoid paraneoplastic syndrome in patients with benign tumours. They present three observations they made (cardiac myxoma, subpleural lipoma and pulmonary fibrosclerotic pseudotumour). Paraneoplasias in these cases are interesting from the pathogenetic aspect as regards their development, possibly malignant transformation of benign intrathoracic tumours.

[The validity of laboratory tests in the diagnosis of alcoholism and alcoholic liver injury]. / Validita laboratórnych vysetrení pre diagnostiku alkoholizmu a alkoholických poskodení pecene.

The authors assessed the value of commonly available laboratory examinations for the diagnosis of suspected excessive alcohol intake and suspected liver damage by alcohol. They tested the validity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gammaglutamyl transferase (GMT), the blood sugar level, serum cholesterol, bilirubinaemia, ferrinaemia and mean corpuscular volume (MCV). The highest validity as regards sensitivity of the examination was recorded in the MCV with a sensitivity of 0.78 and examination of GMT with a sensitivity of 0.72. By combination of MCV and GMT in an alternative manner, the sensitivity rose to 0.87. Evaluation of the groups by the method of discrimination analysis, using all ten parameters, revealed the possibility of 100% correct classification of non-alcoholic subjects and a 86.2% correct qualification of alcoholic subjects.

Success rates of unilateral vs. bilateral cataract extraction in dogs.

Postoperative results of 113 unilateral and 77 bilateral extracapsular cataract extractions (EC-CEs) in dogs were evaluated retrospectively. Restoration or improvement of functional vision was achieved in 79.6% of the eyes in dogs with unilateral extraction and 85.7% of the eyes in dogs with bilateral extractions at weeks 4 to 6. Complications occurring 6 weeks to 9 months after lens extraction lessened the surgical success rate in both groups. Twenty-six percent of the dogs in which bilateral lens removal was performed suffered complications resulting in surgical failure in one eye. When using the criterion that one or both treated eyes had functional vision, a short-term success rate of 98.7% was found for bilateral extractions.

[Paraneoplastic syndromes in internal medicine]. / Paraneoplastické syndrómy vo vnútornom lekárstve.

Paraneoplastic syndromes supplement the complex clinical picture of malignomas. Their knowledge improves early diagnosis. The development, course and regression of paraneoplastic syndromes indicates that they have a multifactorial origin and their manifestation depends on the biochemical, metabolic and immunological situation of the organism. The pathogenesis involves many obscure points and the clinical picture is often a surprise, an unexpected variant with regard to theoretical expectations. Sometimes paraneoplastic syndromes prove fatal in patients with a tretable tumour. There does not exist any paraneoplastic syndrome specific for a certain malignoma. In the authors' group of 1538 patients with malignant tumours belonging into the competence of internal medicine a paraneoplastic syndrome was found in 282 (18.3% patients). In 144 (9.4%) it was the first symptom of disease, incl. 74 (4.8%) where it was also an early sign of the disease. In the group thrombohaemorrhagic and rheumatological paraneoplastic syndrome was most frequently encountered. The relatively highest incidence of early paraneoplasias was observed in those malignomas which affect the immunocompetent apparatus (immunocytomas, haemoblastoses, and lymphomas). The authors recommend that suspect paraneoplastic syndromes should be dispensarized as precanceroses.

[Effect of decane-1,10-bis[acetoxy-(N, N)-dimethyl-(N)-(diphenylmethoxy-2-ethyl) ammonium] dichloride on metabolism in white rats]. / Vliianie dekan-1,10-bis[atsetoksi-(N, N)-dimetil-(N)-(difenilmetoksi-2-étil) ammonii] dikhlorida na obmen veshchestv u belykh krys.

Intramuscular injections of the title drug in a dose of 5 mg/kg (5% of the LD50) during 10 days produced in the liver and blood serum of white rats a decrease in the activity of glucokinase, succinate dehydrogenase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione reductase, ATPase and ceruloplasmin. The urea content in total phospholipids rose, whereas the content of triglycerides and hexosamine diminished. Ten and 20 days after the drug was discontinued the majority of these characteristics returned to normal. The activity of glucosophosphate isomerase, transketolase, glucose-6-phosphatase, fructose-1,6-diphosphatase and lactate dehydrogenase as well as the content of total cholesterol, free fatty acids, tyrosine, hydroxyproline, total protein, RNA and DNA remained unchanged.

Early paraneoplastic syndrome in medical oncology: clinicopathological analysis of 1694 patients treated over 20 years.

During the period of 1963-1982 we treated at our hospital 1694 patients with diagnosed internal malignancies. Of them, paraneoplastic syndrome as the first manifestation of the disease was found in 127 (7.4%). In 79 patients (4.6%) this first symptoms has also been an early manifestation of the malignoma (good general condition, without typical clinical symptoms of cancer). The paraneoplastic syndrome as the first symptom of the disease was manifested mainly as rheumatologic (58 patients; 3.4%) and thrombophlebitis (33 patients; 1.9%) symptoms. While thrombophlebitis as the first symptom of the disease was at the same time only in 48% also an early symptom, rheumatologic syndromes were also early symptoms in as many as 74% of cases. Hemoblastoses, lymphomas, and plasmacytomas are diseases which were accompanied by a paraneoplastic syndrome not only as the first but also as an early manifestation of the disease.

[Quantitative determination of ceruloplasmin activity in rat tissues]. / Kolichestvennoe opredelenie aktivnosti tseruloplazmina v tkaniakh krys.

The suggested method consists in incubation of the homogenate of the tissue under study with a solution of 0.5% p-phenylene diamine hydrochloride. The forming stained products of the reaction are extracted with butanol. The extracts obtained is photometered at a wave of 582 nm. The activity of ceruloplasmin is expressed by arbitrary units per 1 mg of protein.