[Decompressive craniectomy in the treatment of posttraumatic edema and the contribution of new diagnostic methods]. / Dekompresivní kraniektomie v lécbe posttraumatického edému mozku a prínos nových monitorovacích metod.

The authors present a case report of a young male who suffered a brain injury complicated with malignant posttraumatic edema managed with bilateral decompressive craniectomy after conservative treatment failure. They further discuss current surgical approach to posttraumatic brain edema and contribution of new diagnostic methods in secondary brain damage management.

MMP-19 deficiency causes aggravation of colitis due to defects in innate immune cell function.

Matrix metalloproteinases (MMPs) are potential biomarkers for disease activity in inflammatory bowel disease (IBD). However, clinical trials targeting MMPs have not succeeded, likely due to poor understanding of the biological functions of individual MMPs. Here, we explore the role of MMP-19 in IBD pathology. Using a DSS-induced model of colitis, we show evidence for increased susceptibility of Mmp-19-deficient (Mmp-19(-/-)) mice to colitis. Absence of MMP-19 leads to significant disease progression, with reduced survival rates, severe tissue destruction, and elevated levels of pro-inflammatory modulators in the colon and plasma, and failure to resolve inflammation. There was a striking delay in neutrophil infiltration into the colon of Mmp-19(-/-) mice during the acute colitis, leading to persistent inflammation and poor recovery; this was rescued by reconstitution of irradiated Mmp-19(-/-) mice with wild-type bone marrow. Additionally, Mmp-19-deficient macrophages exhibited decreased migration in vivo and in vitro and the mucosal barrier appeared compromised. Finally, chemokine fractalkine (CX3CL1) was identified as a novel substrate of MMP-19, suggesting a link between insufficient processing of CX3CL1 and cell recruitment in the Mmp-19(-/-) mice. MMP-19 proves to be a critical factor in balanced host response to colonic pathogens, and for orchestrating appropriate innate immune response in colitis.

Arteriovenous fistula as a complication of renal biopsy.

BACKGROUND: We evaluated the incidence and history of arteriovenous fistula (AVF) after kidney biopsy and assessed the use of superselective embolisation for treatment. METHODS: Case report of a 10-year-old boy with nephrotic syndrome. Renal biopsy (RB) in this patient was complicated with AVF. Immediately after RB was undertaken, microscopic haematuria was observed, within 48 hours after the biopsy life-threatening haematuria due to pseudoaneurysm started. Renal angiography was carried out, which demonstrated a hyperthrophic aberrant artery in the region of the bottom pole of the left kidney, from which blood was instantaneously flowing through a high-flow arteriovenous fistula (AVF). RESULTS: Embolization was carried out using small platinum coils (MWCE-18S-3/2, -18S-4/2, -18S-5/2TORNADO Embolization Microcoil) and the tissue adhesive Histoacryl. CONCLUSIONS: The technique of superselective embolisation using coaxial catheter is a safe method in the treatment of post biopsy AVFs and pseudoaneurysm (Fig. 3, Ref. 6).

[Diagnostics and treatment of hepatocellular carcinoma. Recommendations of the Portal Hypertension Working Group of the Czech Hepatology Society and the J.E. Purkinje Czech Medical Society ]. / Diagnostika a lécba hepatocelulárního karcinomu.

Hepatocellular carcionma (HCC) is almost exclusively associated with liver cirrhosis as a significant HCC risk marker in advanced countries. Applicable therapy depends on early diagnosis, and risk patients should be screened for the presence of HCC on a regular basis. Liver ultrasound and determination of alpha-fetoprotein serum levels (AFP) are the screening methods used. Spiral CT is the most often used method for HCC staging. Non-invasive methods may under certain circumstances replace aimed biopsy. There are 3 basic curative therapies for the early stage of HCC: liver transplantation, surgical resection and different methods of local destruction of tumour (i.e., ethanolisation, thermoablation, etc.). Patients at medium stage of HCC may profit from chemoembolisation. Current available systemic chemotherapy is ineffective. Patients with advanced HCC are treated symptomatically. Patient survival prognosis after the application of one of the above treatment methods may be similar with that for HCC free cirrhosis patients, however, prognosis for advanced HCC patients is bad, with survival period from one to nine months.

Effect of intermittent high altitude hypoxia on the synthesis of collagenous and non-collagenous proteins of the right and left ventricular myocardium.

The incorporation of 14C-proline into collagenous and non-collagenous proteins of the right and left ventricular myocardium was investigated in rats exposed to intermittent high altitude hypoxia. Experimental results have shown that even in control animals significant differences exist in the concentration and synthesis of individual protein fractions between the right and left ventricular myocardium. Long-term exposure to intermittent high altitude hypoxia induced a significantly increased concentration of collagenous and non-collagenous proteins in both ventricles. The incorporation of 14C-proline was not affected at this period (ie period of stabilised hypertrophy) in either of the fractions studied.

Functional changes in the right and left ventricle during development of cardiac hypertrophy and after its regression.

OBJECTIVE: The aim was to determine left and right ventricular functional reserves and collagen concentration during the development of cardiac hypertrophy and after its regression. METHODS: Two experimental models of cardiac hypertrophy (chronic thyroxine or isoprenaline treatment of adult rats) were compared 24 h and five weeks after the agent was last given. Pressure changes in the left (right) ventricle before and after acute aortic (pulmonary artery) ligation were recorded in open chest anaesthetised animals. The difference in dP/dtmax after and before ligation was regarded as the functional reserve. The total collagen concentration was determined in both ventricles separately by means of hydroxyproline. RESULTS: Left and right ventricular weight increased by 20% and 30% respectively in the two models employed. In the thyroxine treated group, the functional reserve of the left ventricle rose very noticeably, whereas in the isoprenaline treated group it decreased. The right ventricular functional reserve did not differ from that in the controls in either of the two groups. The collagen concentration rose in the left ventricle in the isoprenaline group only. Five weeks after the last administration of the agent, cardiac mass and ventricular function did not differ from the control values in either of the models studied; the only exception was the incomplete regression of left ventricular hypertrophy and persistent structural and functional impairment of the left ventricle in the isoprenaline treated group. CONCLUSIONS: Our results indicate that hearts undergoing a comparable degree of experimental hypertrophy may have different functional and structural properties; significant differences were found between the right and left ventricular response. Regression of hypertrophy together with a reversal of ventricular function usually occurs unless the myocardium has received severe structural damage.

Intermittent high altitude hypoxia.

The effect of intermittent high altitude (IHA) hypoxia on the myocardium and lesser circulation was investigated in adult male Wistar rats. IHA can induce intermittent pulmonary hypertension and right ventricular hypertrophy in a relatively short time. Even marked pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular changes can be normalized when rats are removed from the hypoxic atmosphere. At the beginning of the exposure to IHA acute myocardial necrotic changes were found; prolongation of IHA did not lead to further acute lesions. Experimentally induced CO polycythemia leads to mild pulmonary hypertension; IHA-induced pulmonary hypertension may, thus, be partly due to polycythemia. Beta blocking agents are able to decrease chronic hypoxic pulmonary hypertension, hypertensive changes in the pulmonary circulation, the degree of right ventricular hypertrophy, and necrotic myocardial changes.

The role of L-carnitine in pediatric cardiomyopathy.

Metabolic and genetic factors underlie some forms of cardiomyopathy in childhood. A variety of inborn errors of metabolism can impair mitochondrial energy production, or beta-oxidation, in the heart and lead to myocardial dysfunction. L-Carnitine, an essential element of beta-oxidation, transports fatty acids across the mitochondrial membrane for energy production. L-Carnitine deficiency syndromes are now well described as secondary to a variety of inborn errors of metabolism and often include cardiomyopathy in the clinical picture. Despite traditional therapies for cardiomyopathy, mortality for this disorder remains at well over 50%. Review of reports of L-Carnitine supplementation studies and results from our own trial underscore the importance of its role in cardiac function and demonstrates that there is likely a subpopulation of patients with cardiomyopathy responsive to L-carnitine treatment.

Cathepsin B, thiols and cysteine protease inhibitors in squamous-cell lung cancer.

We investigated activities of the cysteine protease cathepsin B (CB; EC 3.4.22.1), the levels of reduced glutathione (GSH) and cysteine and the activity of gamma-glutamyltransferase (gamma-GT; EC 2.3.2.2) in squamous-cell lung carcinoma (SQCLC) and the lung parenchyma specimens from surgically treated patients. The basal CB activity, assayed in tissue extracts in the absence of exogenous activators, was significantly higher in SQCLC compared to the lung. The residual CB activity, remaining in tissue extracts after preincubation at 37 degrees C, was not any longer significantly different in SQCLC and the lungs. The inhibited CB activity, calculated as the difference between the basal and residual CB activities, was significantly higher in SQCLC compared to the lung. In the case of the cysteine protease cathepsin C (CC; EC 3.4.14.1), neither the basal nor the residual nor the inhibited CC activities in SQCLC and the lung were significantly different. Compared to CC, the powerfulness of endogenous cysteine protease inhibitors to inhibit CB was much higher in both SQCLC and the lung. The cysteine protease inhibitors from SQCLC and the lung which effectively inhibited CB could be related to the inhibitors with an apparent M(r) ranging from 10,000 to 30,000. Isoelectric focusing studies indicated significant differences in the progress of inhibition of the activity of CB isoforms in SQCLC and lung parenchyma extracts. The levels of both GSH and Cys were significantly higher in SQCLC compared to the lung and the level of GSH was significantly higher in Stage III tumors compared to Stage I tumors. The activity of gamma-GT was not significantly different in SQCLC and the lung but it was significantly higher in Stage I tumors compared to Stage III tumors and showed a significant negative correlation with GSH level in SQCLC. Dithiothreitol did not increase the basal activity of CB from SQCLC and the lung which indicates that reversibly oxidized forms of CB do not accumulate in the tumors and the lungs. The basal activity of CB from SQCLC and the lung was competitively inhibited by Cys. Moreover, increasing Cys concentrations had a modulatory effect on the basal activity of CB from SQCLC and the lung which was featured by Cys-induced inhibition of CB activity and by subsequent Cys-effected recovery of CB activity from its previous inhibition by Cys.

Cysteine proteases and cysteine protease inhibitors in non-small cell lung cancer.

In this study we investigated the levels of two lysosomal cysteine protease proteins cathepsin B (CB) and cathepsin L (CL) and the levels of three cysteine protease inhibitor proteins stefin A (SFA), stefin B (SFB) and cystatin C (CNC) in squamous-cell lung carcinoma (SQCLC) and matched lung parenchyma specimens and examined the inhibition of CB and cathepsin C (CC) activities by endogenous inhibitors in extracts from SQCLC, lung adenocarcinoma (LAC) and lung parenchyma specimens. We found that Stage I SQCLCs contained significantly increased levels of CB protein, CB activity and SFA protein as compared to matched lungs. Neither the levels of CL protein nor the levels of SFB protein nor the levels of CNC protein in Stage I SQCLCs and the lungs were significantly different, but the levels of CB and CL proteins as well as the levels of SFA and SFB proteins showed significant positive correlation in SQCLCs. In SQCLCs as well as in the lungs the level of SFB protein was significantly higher than the level of SFA protein or the level of CNC protein. In the lungs the levels of SFA protein and CNC protein revealed a weak negative correlation trend. In extracts from SQCLCs the level of SFA protein showed a weak negative correlation with the residual CB activity (i.e. the activity remaining after extract preincubation) whereas in extracts from the lungs the level of CNC protein displayed a weak negative correlation trend with the residual CB activity and with the residual CC activity. We observed that SQCLCs and LACs contained not only a significantly increased activity of CB but also a significantly higher inhibitory potential against the activity of endogenous CB as compared to matched lungs. Leupeptin, a small inhibitor of CB, was capable to protect CB in lung carcinoma and lung parenchyma extracts from preincubation-induced inhibition, revealing an active-site directed and competitive nature of CB inhibition by endogenous cystatins. Ultrafiltration passaged protein preparations of nominal Mr < or = 30,000 obtained from extracts of SQCLCs inhibited significantly higher quantities of activity of purified bovine spleen CC than did such protein preparations from matched lungs. Reaction courses of purified bovine spleen CC that had been preincubated with such protein preparations resembled those of endogenous CC from SQCLC and lung extracts showing a slow steady-state approach. These observations and the relaxation kinetics of CC from SQCLC and lung extracts suggest that CC in the extracts may be complexed with some cystatins. In conclusion, our results indicate that quantitatively different combinations of cystatins are the major constituents of the inhibitory potential against CB and CC in SQCLCs and the lungs.

Aminopeptidases and angiotensin I-converting enzyme activities in primary human lung tumors and lung parenchyma.

The activities of alanyl aminopeptidase (AAP), arginyl aminopeptidase (RAP), alpha-glutamyl aminopeptidase (EAP) and angiotensin I-converting enzyme (ACE) were investigated in primary human lung tumors of different histological types and in matched lung parenchyma. In contrast to the studied aminopeptidases whose activity differences between tumor and lung tissues were infrequently significant, the activity of ACE was decreased highly significantly in the majority of lung tumors.

The contribution of discrimination analysis to the diagnostic decision in patients with lung carcinoma.

A set of 620 patients was examined. Out of them, 245 suffered from lung carcinoma of different type and stage, 28 suffered from other malignant tumors, 37 were affected with benign tumors, and 166 were suffering from a nonmalignant respiratory disease (tuberculosis, nonspecific pneumonia, chronic bronchitis, abscesses, cysts, asthma, lung fibrosis, bronchiectasis and sarcoidosis). In addition to these patients, 144 blood donors were examined who represented the control group of healthy individuals. In a blind test another set of 266 persons was examined. By completing the values of selected markers (orosomucoid, prealbumin, glycoprotein electrophoresis, erythrocyte sedimentation, age of the individual, and the number of smoked cigarettes) into the discrimination rule and by calculating the discrimination function, a sensitivity of 80.6% and a specificity of 75.6% were obtained. A comparative cytological examination of the same set revealed lower sensitivity (61.0%) but higher specificity (98.0%). These values were verified in a blind test, as the patients were admitted to the hospital. Sensitivity in lung cancer was found to be 83.9%; in nonmalignant diseases the respective value was 77.1%. This approach can be applied to individuals suspect of cancer, in secondary prevention and in individuals with a high risk of lung cancer.

Lysosomal dipeptidyl-peptidases I and II in human squamous cell lung carcinoma and lung parenchyma.

In the present work we studied the levels of activities of dipeptidyl-peptidase I (or cathepsin C, DPP-I) and dipeptidyl-peptidase II (DPP-II) and examined their isoelectric focusing profiles in matched pairs of human squamous cell lung carcinoma (SQCLC) and the lung from surgically treated patients (n = 33). The mean specific activities of DPP-I and DPP-II were higher in SQCLC (Stages I and II) than in the lung, but only the activity of DPP-II in Stage I SQCLC was significantly higher compared to the lung. The activities of both enzymes were higher in the tumor than in the lung in 10 of 20 Stage I SQCLC patients, but only in 3 of 13 Stage II SQCLC patients. The specific activities of DPP-I and DPP-II in the lungs showed a good correlation while the correlation of both enzyme activities in SQCLCs was poor. We observed only a small and mutually comparable activation of DPP-I in extracts from SQCLCs and from the lungs by dithiothreitol. The isoelectric focusing profile of several DPP-II forms in SQCLCs and the lungs was similar and the single major DPP-II isoform revealed in the tumors and lungs showed a pIapp of 5.3-5.2. The isoelectric focusing profile of DPP-I showed multiple enzyme forms in SQCLCs (pIapp 6.3-4.5) as well as in the lungs (pIapp 6.4-4.8). In SQCLCs, as well as in the lungs, the activities of the DPP-I forms with pIapp values < or = 5.6 were shifted by neuraminidase treatment to the site of the major DPP-I isoform with pIapp of about 6.0 and the zymograms then showed an another DPP-I with pIapp of 5.7, which was less discernible in the lung. In some patients, the DPP-I forms with pIapp values < or = 5.6 from SQCLC retained a greater percentage of activity distribution than did the DPP-I pIapp-counterparts from the lung.

Arteriovenous malformations of the orofacial area.

Vascular lesions are pathological residues of the embryonic vascular system and can be divided into two main groups. The first group comprises haemangiomas, which are typical of childhood and involute spontaneously. The second group is formed by lesions without active proliferation, which include, among others, arteriovenous malformations that are congenital and grow proportionately with the subject. The authors present two cases of arteriovenous malformations of the orofacial area and discuss possibilities for modern diagnosis and treatment. Precise diagnosis and effective treatment of vascular lesions should be ensured by a diagnostic and therapeutic team of specialists from several disciplines (maxillofacial, ENT, plastic and general surgeon, paediatrician, haematologist, anaesthesiologist and possibly a neurosurgeon), headed by an intervention radiologist.

[Clinical and ultrasonic diagnosis of congenital hip dislocation (dynamics of changes in early therapy)]. / Klinická a ultrasonografická diagnostika vrozeného vykloubení kycelních kloubu (dynamika zmen pri vcasné terapii).

The authors present part of their prospective epidemiological study of congenital dysplasia of hip joints within which newborns were examined by ultrasonogram prior to the beginning of the therapy. Apart from the standard examination in the frontal plane after Graf they examined on principle also the ultrasonographic stability by the dynamic test after Schuler as well as by the application of the probe anteriorly with the simultaneous provocation according to Palmén. The authors have processed pathological ultrasonographic findings in 53 newborns (64 hip joints). The technique of the examination by ultrasound from the anterior approach is explained in detail. The comparison of both dynamic tests has shown that the examination from the anterior approach is considerably more sensitive than Schuler's dynamic test and also fully correlates with the clinical finding. It is a fact that the shift of the head in the flexion dorsally represents the most important component of the movement in unstable hip joint during provocation, it is far more noticeable than the lateralization of the head or the shift in the cranial direction. After achieving ultrasonographic stability the classical Graf method is sufficient for the registration of residual changes on the acetabular rim. The follow-up of patients until their complete healing has shown a surprisingly rapid remodellation of hip joints. The whole complex of clinically unstable hip joints has been divided into subgroups according to Graf classification. In type IIc or IId on the basis of ultrasonographic examination from the anterior approach the stable joints from the ultrasonographic viewpoint have been distinguished from unstable ones. The follow-up carried out in short intervals has shown that of longest duration is the remodellation of total dislocation and, on the contrary, of shortest duration is the healing of joints in the IIc or IId type. An absolute majority of affected hip joints have become normal until 3rd month of the age. The complex does not include two patients with teratological dislocation, the incidence of which has been determined in our study by the ratio of 2 cases in 35,550 of timely examined newborns. The role of the factor of spontaneous stabilization cannot be in this part of the study completely discounted. However, herewith we present part of an accomplished epidemiological study where the number of timely diagnosed patients including late diagnoses corresponds to the number of dislocations and subluxations determined within the conventional late diagnosis.

[Defects of the atrioventricular cardiac septum (persistent common atrioventricular canal)]. / Defekty atrioventrikulárního srdecního septa (canalis atrioventricularis communis persistens).

A new morphological-clinical classification was suggested for this type of heart malformations based on confrontation of authors' results with literature. The classification took into consideration appearance of the top of ventricular septum, form of atrioventricular valves, topography of the defect and its relation to the location of conducting system.

[Lipostat in the treatment of hyperlipoproteinemia]. / Lipostat v lécbe hyperlipoproteinémií.

Within the framework of clinical tests of LIPOSTAT (pravastatin tablets 20 mg Bristol Meyers-Squibb Co.) this hypolipidaemic preparation was administered to 28 patients with different types of hyperlipoproteinaemias, mainly of type IIa. Administration for a period of four weeks--20 mg in the evening--had a significant effect on several basic indicators of the lipid metabolism. The total plasma cholesterol level declined by 20%, the apolipoprotein B level by 11%, the HDL cholesterol level rose by 38% and the triacylglycerol level declined by 18%. During administration the serum levels of aminotransferases, creatine kinase and alkaline phosphatase did not increase. No adverse side-effects were observed which called for discontinuation of treatment. Pravastatin is according to the authors' experience and the results of others an effective hypolipidaemic agent, suitable for the majority of patients with hyperlipoproteinaemias, in particular those with elevated plasma cholesterol levels.

[Ambulatory monitoring of blood pressure in regular dialysis therapy]. / Ambulantní monitorování krevního tlaku v pravidelném dialyzacním lécení.

Ambulatory monitoring of the blood pressure (AMBP) makes it possible to diagnose in hypertensive patients the so-called dipper phenomenon, i.e. a drop of the BP during the night provided that the patient is asleep. The absence of this phenomenon implies as a rule serious damage of the cardiovascular apparatus, brain or kidneys. By means of an apparatus ABP monitoring type 90207 of Space Labs. Inc. a group of 16 patients in regular dialysis treatment (RDT) was examined and the blood pressures were evaluated before and after dialysis. Patients with the dipper profile reacted more adequately during dialysis i.e. by a drop of the blood pressure due to the loss of excessive fluid which they retained during the interdialysis period, as compared with the group with a non-dipper profile which may be exposed to a greater risk of cardiovascular complications. The authors conclude that detection of the absence of the non-dipper phenomenon can reveal risk patients. AMBP can explain so-called paradoxical hypertension at the end of haemodialysis despite major removal of fluids by ultrafiltration, and that moxonidine participates in a significant way in the elimination of the non-dipper phenomenon.

[C-reactive protein in diagnosis of complications in renal insufficiency and failure]. / C-reaktivní protein v diagnostice komplikací pri ledvinové nedostatecnosti a selhání.

C-reactive protein (CRP) is one of the positive proteins in an acute phase. It is produced in hepatocytes in response to cytokines activity, especially to IL-6. Its increase is the second biggest after significant bacterial and cardiovascular insults. It reaches its peak between 24 and 48 hours. CRP monitoring makes possible monitoring of the intensity of the pathologic process and to control efficiency of treatment measures according to fluctuation of its level. According to its serum values it can reflect a place of inflammation, e.g. in upper or lower airways, urinary tract etc. It helps to distinguish between bacterial and viral inflammations and to identify size of vascular lesions such as acute myocardial infarction, cerebral infarction, decompensation of atherosclerosis. Because of its easy detection and quick elevation CRP has not only a diagnostic importance but also a prognostic one and is a predictor of a risk of atherosclerosis. Although long lasting renal insufficiency (LLRI), renal failure (RF) and regular dialysis treatment (RDT) are indicated to elevate CRP level, authors present proves that adequately treated patient compensated with an adequate dialysis treatment has normal CRP values for a long time in spite of long lasting comorbidities including atherosclerosis. There has been done a long term monitoring of 10 patients with LLRI and 22 patients with RDT. Their CRP was monitored via a turbidimetric method using sets K-Assay made by company Kamya Bio Comp. Elevated CRP in the samples reflects an acute insult such as infection, cardiovascular disease, diabetes decompensation and last but not least quality of a dialysis treatment.

[Postoperative atrioventricular and intraventricular block in tetralogy of Fallot. Electrophysiology study]. / Pooperacní sínokomorové a nitrokomorové blokády u Fallotovy tetralogie, elektrofyziologická studie.

One of the causes of the late deaths after operations of the tetralogy of Fallot are dysrhythmias caused by impaired conduction and automatism. To assess the severity and site of the atrioventricular and intraventricular block the authors used in 19 patients after operation of the tetralogy of Fallot an invasive electrophysiological examination. The authors recommend, based on their own experience, to follow-up on a long-term basis all patients with temporary postoperative complete a-v block. The presence of bifascicular or temporary postoperative a-v block alone does not yet imply the need of a permanent pacemaker. If a serious a-v block persists after the third week or if a syncope or cardiac weakness develops, the authors indicate a permanent pacemaker. Also the development of trifascicular block, even in patients with a normal P-Q interval, detected during fever, physical work or during electrostimulation of the atria is an indication for the introduction of a permanent pacemaker.