p16INK4a as an adjunct test in cervical cytology.

BACKGROUND: This study investigated the correlation between cervical cytology, the expression of P16INK4a, and human papilloma virus (HPV) infection. MATERIALS AND METHODS: The study included 100 subjects with suspected pathological cervical lesions. Cervical smears were analyzed for malignancy and p16INK4a. Histological finding represented "the golden standard". RESULTS: Immunocytochemical analysis of protein p16INK4a expression on epithelial cells of cervical smear demonstrated increased p16lNK4a expression in 36.0% of subjects. There was statistically significant positive correlation (Spearman r = 0.70; p < 0.001) between the pathological findings and the intensity of p16INK4a protein expression inside the epithelial cells, as well as with the histological finding (Spearman r = 0.71; p < 0.001). The intensity of p16INK4a protein expression in cytology finding was significantly higher in HPV16 positive patients (Mann- Whitney test, p = 0.0065). CONCLUSION: Good correlation between the expression rate and the severity of lesions indicates that this test might improve the results of cytology and HPV screening, as well as the results of predicting the prognosis of the disorder of the cervix.

Catecholaminergic signalling through thymic nerve fibres, thymocytes and stromal cells is dependent on both circulating and locally synthesized glucocorticoids.

Glucocorticoids have been shown to modulate the expression of noradrenaline metabolizing enzymes and ß(2)- and α(1B)-adrenoceptors in a tissue- and cell- specific manner. In the thymus, apart from extensive sympathetic innervation, a regulatory network has been identified that encompasses catecholamine-containing non-lymphoid and lymphoid cells. We examined a putative role of adrenal- and thymus-derived glucocorticoids in modulation of rat thymic noradrenaline levels and adrenoceptor expression. Seven days postadrenalectomy, the thymic levels of mRNAs encoding tyrosine hydroxylase, dopamine ß-hydroxylase, monoamine oxidase-A and, consequently, noradrenaline were decreased. Catecholamine content was diminished in autofluorescent nerve fibres (judging by the intensity of fluorescence) and thymocytes (considering HPLC measurements of noradrenaline and the frequency of tyrosine hydroxylase-positive cells), while it remained unaltered in non-lymphoid autofluorescent cells. In addition, adrenalectomy diminished the thymocyte expression of ß(2)- and α(1B)-adrenoceptors at both mRNA and protein levels. Administration of ketoconazole (an inhibitor of glucocorticoid synthesis/action; 25 mg kg(-1) day(-1), s.c.) to glucocorticoid-deprived rats increased the thymic levels of tyrosine hydroxylase, dopamine ß-hydroxylase and, consequently, noradrenaline. The increased intensity of the autofluorescent cell fluorescence in ketoconazole-treated rats indicated an increase in their catecholamine content, and suggested differential glucocorticoid-mediated regulation of catecholamines in thymic lymphoid and non-lymphoid cells. In addition, ketoconazole increased the thymocyte expression of α(1B)-adrenoceptors. Thus, this study indicates that in the thymus, as in some other tissues, glucocorticoids not only act in concert with cateholamines, but they may modulate catecholamine action by tuning thymic catecholamine metabolism and adrenoceptor expression in a cell-specific manner. Additionally, the study indicates a role of thymus-derived glucocorticoids in this modulation.

Cervical conization--treatment for cervical intraepithelial neoplasia and carcinoma in situ.

PURPOSE: Cone biopsy is the best treatment for high-grade premalignant cervical changes. Cervical intraepithelial changes do not show any clinical picture until the process develops into carcinoma. METHOD: This retrospective study included 395 women who underwent conization at Gynecology and Obstetrics Clinic "Narodni front" during 2009. The chi-square test was used for comparing results. RESULTS: Pathohistological findings from biospy and conization were identical in 40.50% of patients, in 10.13%, the conization finding was more severe than the biopsy finding, while in 49.37% less severe than the biopsy finding. Resection margins status analysis showed that 12.66% of cones were positive. Comparison between cones with positive margins and operative techniques did not show any statistically significant difference; 64% of women with positive margins were over the age of 35. CONCLUSION: Operative conization techniques are equally represented. However in women over the age of 40 scalpel excision methods are recommended. In women over the age of 45 there is a statistically significant increase in the risk for positive resection margin with CIN3 and glandular lesions.

Ultrasonographic examination of the liver circulation in patients with liver metastasis from colorectal cancer.

PURPOSE: Conventional imaging modalities are presently recommended for the detection of liver metastases. However, the presence of liver micrometastases is a major diagnostic problem. It has been known that micrometastases could be associated with changes in the liver blood flow. METHODS: We examined several parameters by color Doppler ultrasound to estimate hepatic artery flow in 30 patients without and 17 patients with liver metastases from colon cancer. RESULTS: Mean values of hepatic artery diameter (4.25 + or - 0.81 mm in patients with liver metastases were not statistically different from those in patients without metastases (3.98 + or - 0.81). Patients with liver metastasis had significantly higher (p=0.007) mean values of systolic speed (61.33 + or - 30.01 cm/s) in comparison to patients without metastasis (41.38 + or - 16 cm/s). CONCLUSION: Based on these results we suggest that color Doppler examination can be an additional quick noninvasive method in the detection of circulatory changes in the estimation of liver metastases.

Synaptic transmission depressed by colchicine blockade of axoplasmic flow.

Colchicine, which inhibits axoplasmic transport and induces organelle alterations in nerve terminals, was injected intraocularly in pigeons. Electrical stimulation of the optic nerve yielded normal evoked potentials in retinotectal fibers, whereas postsynaptic responses recorded in the tectum were reduced. Postsynaptic depression suggests a deficit of synaptic transmission, presumably dependent on colchicine interference with migrating material.

Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level.

To test putative interdependence in the ontogenesis of the hypothalamic-pituitary-gonadal and thymic-lymphatic axes, thymocyte differentiation and maturation was examined in neonatally castrated (Cx) adult rats. In the hypercellular thymi of Cx rats, the proportion of the least mature CD4(-)CD8(-)TCRalphabeta(-) triple negative (TN) thymocytes was reduced, while the proportions of all downstream double positive (DP) subsets (TCRalphabeta(-), TCRalphabeta(low) and TCRalphabeta(high)) were increased when compared with neonatally sham-castrated (Sx) adult rats. This suggested an accelerated thymocyte transition from the TN to DP TCRalphabeta(low) developmental stage accompanied by an increased positive/ reduced negative thymocyte selection. The increased thymocyte surface density of Thy-1, which is implicated in thymocyte hyposensitivity to negative selection, in Cx rats further supports the previous assumption. The finding that the proportions of both single positive (SP) TCRalphabeta(high) thymocyte subsets were reduced, while their numbers were increased (CD4(+)CD8(-)) or unaltered (CD4(-)CD8(+)), coupled with results demonstrating an increased level of CD4(-)CD8(+) cells without changes in that of CD4(+)8(-) cells in the spleen indicate: (i) accelerated differentiation and maturation of the positively selected DP TCRalphabeta(high) thymocytes towards CD4(-)8(+) TCRalphabeta(high) cells followed by increased emigration of the mature cells and (ii) decelerated differentiation and maturation towards CD4(+)8(-)TCRalphabeta(high) cells in Cx rats. Furthermore, the unaltered proportion of intrathymically developing CD4(+)CD25(+)Foxp3(+) regulatory cells in Cx rats, in light of putative hyposensitivity of thymocytes to negative selection suggesting reduced elimination of autoreactive cells, may provide a firm basis for understanding the reasons behind increased susceptibility of Cx rats to autoimmune disease induction.

Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats.

Age-related increase in the density of thymic noradrenergic fibres and noradrenaline (NA) concentration is proposed to be associated with thymic involution and altered thymopoiesis. To test this hypothesis thymocyte differentiation/maturation and thymic structure were studied in 18-month-old male Wistar rats subjected to 14-day-long propranolol (P) blockade of beta-adrenoceptors (beta-ARs). The treatment primarily resulted in changes in the T-cell receptor (TCR)-dependent stages of thymopoiesis, which led to an increase in both the relative and absolute numbers of the most mature single positive (SP) CD4(+)CD8(-) (including cells with the CD4(+)CD25(+) regulatory phenotype) and CD4(-)CD8(+) TCRalphabeta(high) thymocytes. Accordingly, in the thymi of these rats an increase in both numerical density and absolute number of medullary thymocytes encompassing mainly the most mature SP cells was found. These findings, together with an increase in the thymocyte surface expression of the regulatory molecule Thy-1 (CD90) (implicated in negative regulation of TCRalphabeta-dependent thymocyte selection thresholds) in the same rats, may suggest increased positive/reduced negative thymocyte selection. Collectively, the results indicate that a decline in thymic efficiency in generating both conventional and regulatory T cells, and consequently in immune function, in aged rats may be, at least partly, attenuated by long-term blockade of beta-ARs with P.

Comprehensive analysis of PM10 in Belgrade urban area on the basis of long-term measurements.

In this study, we investigated the impact of potential emission sources and transport pathways on annual and seasonal PM10 loadings in an urban area of Belgrade (Serbia). The analyzed dataset comprised PM10 mass concentrations for the period 2003-2015, as well as their chemical composition (organic/elemental carbon, benzo[a]pyrene, As, Cd, Cr, Mn, Ni, Pb, Cl(-), Na(+), Mg(2+), Ca(2+), K(+), NO3 (-), SO4 (2-), and NH4 (+)), meteorological parameters, and concentrations of inorganic gaseous pollutants and soot for the period 2011-2015. The combination of different methods, such as source apportionment (Unmix), ensemble learning method (random forest), and multifractal and inverse multifractal analysis, was utilized in order to obtain a detailed description of the PM10 origin and spatio-temporal distribution and to determine their relationship with other pollutants and meteorological parameters. The contribution of long-range and regional transport was estimated by means of trajectory sector analysis, whereas the hybrid receptor models were applied to identify potential areas of concern.

Differential effect of acetylsalicylic acid and dipyrone on prostaglandin production in human fibroblast cultures.

Human skin fibroblasts incubated with arachidonic acid in culture show basal release of prostaglandins. They produce the same prostaglandins after stimulation with bradykinin. Basal release of prostaglandins I2 (6-oxo-PGF1 alpha), F2 alpha and E2 is inhibited dose-dependently by both acetylsalicylic acid (ASA) and dipyrone (P less than 0.05). The examined dose-range was 10(-7) to 10(-4) M for both drugs. During the first 5 min after removal of the drugs from the incubation medium, bradykinin-stimulated release remains dose-dependently inhibited (P less than 0.001) in ASA-, but not in dipyrone-treated cultures. The difference between the effects of ASA and of dipyrone is highly significant (P less than 0.0001), whereas the dipyrone-treated cultures are not different from controls. The findings are consistent with cyclo-oxygenase inhibition by ASA as well as by dipyrone. However, the data demonstrate rapid reversibility of the effect of dipyrone. This suggests that in contrast to ASA, dipyrone does not inhibit cyclo-oxygenase by binding covalently to the enzyme.

Antihypertensive efficacy and tolerance of penbutolol: results of a co-operative study in 227 patients.

An open, co-operative study was carried out in 227 patients with mild to severe essential hypertension to assess the efficacy and tolerance of penbutolol, given as monotherapy, in controlling blood pressure. Patients received a single daily dose (40 mg in the majority) for 8 weeks and were assessed every 2 weeks. The results showed that there was a significant reduction (p less than 0.01) in systolic, diastolic and mean arterial blood pressure and in pulse rate after 2 weeks compared with pre-treatment values, and there was a further significant reduction (p less than 0.01) comparing 8-week values with those measured after 2 weeks. Response to treatment did not differ significantly between those patients who were newly diagnosed and those who had received previous antihypertensive medication. The largest percentage reduction in blood pressure from initial values was recorded in those patients with the more severe hypertension (diastolic 116 to 130 mmHg) and a considerable number of all the patients became normotensive during the trial period. Records of side-effects indicated a global incidence of 17.6%, the most frequently reported being dizziness and mild gastro-intestinal disorders; only 1 patient complained of bradycardia and another of cold extremities. Eighteen (7.9%) patients dropped out of the study due to side-effects.

The effect of the converting enzyme inhibitor HOE 498 on the renin angiotensin system of normal volunteers.

The converting enzyme inhibitor HOE 498 was evaluated in 12 normotensive male volunteers aged 21 to 26. The efficacy of single 5, 10 or 20 mg oral doses in blocking the pressor response to exogenous angiotensin I was tested in 3 of the subjects. All 3 doses of HOE 498 reduced the pressor response to exogenous angiotensin I to below 50% of control within 1,5 h following administration of the drug. Plasma renin and converting enzyme activity, blood angiotensin I, as well as plasma angiotensin II and aldosterone were measured serially before and up to 72 h following oral administration of a single dose of 2.5, 5, 10 or 20 mg of HOE 498 to groups of 5 volunteers each. As expected, blood angiotensin I levels and plasma renin activity rose while plasma converting enzyme activity, plasma angiotensin II and aldosterone concentration fell after administration of the drug. While the dose of 2.5 mg did not reduce plasma converting enzyme activity below 20% of control, the higher doses all resulted in plasma converting enzyme inhibition exceeding 90%. No side-effects were observed. It is concluded that in normal volunteers HOE 498 is an effective potent and long-acting converting enzyme inhibitor. Based on these preliminary findings it is expected that 5 mg HOE 948 will turn out to be adequate for therapeutic use.

Cellular and nerve fibre catecholaminergic thymic network: steroid hormone dependent activity.

The thymus plays a critical role in establishing and maintaining the peripheral T-cell pool. It does so by providing a microenvironment within which T-cell precursors differentiate and undergo selection processes to create a functional population of major histocompatibility complex-restricted, self-tolerant T cells. These cells are central to adaptive immunity. Thymic T-cell development is influenced by locally produced soluble factors and cell-to-cell interactions, as well as by sympathetic noradrenergic and endocrine system signalling. Thymic lymphoid and non-lymphoid cells have been shown not only to express beta- and alpha(1)- adrenoceptors (ARs), but also to synthesize catecholamines (CAs). Thus, it is suggested that CAs influence T-cell development via both neurocrine/endocrine and autocrine/paracrine action, and that they serve as immunotransmitters between thymocytes and nerves. CAs acting at multiple sites along the thymocyte developmental route affect T-cell generation not only numerically, but also qualitatively. Thymic CA level and synthesis, as well as AR expression exhibit sex steroid-mediated sexual dimorphism. Moreover, the influence of CAs on T-cell development exhibits glucocorticoid-dependent plasticity. This review summarizes recent findings in this field and our current understanding of complex and multifaceted neuroendocrine-immune communications at thymic level.

Glucocorticoids, master modulators of the thymic catecholaminergic system?

There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg.100 g body weight-1.day-1) for 4 days. The effects of beta-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCRalphabetahigh thymocytes as revealed by two-way ANOVA; for CD4+CD8- F (1,20) = 10.92, P < 0.01; for CD4-CD8+ F (1,20) = 7.47, P < 0.05], a skewed thymocyte maturation towards the CD4-CD8+ phenotype, and consequently a diminished CD4+CD8-/CD4-CD8+ mature TCRalphabetahigh thymocyte ratio (3.41 +/- 0.21 in non-adrenalectomized rats vs 2.90 +/- 0.31 in adrenalectomized rats, P < 0.05) were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only beta-adrenoceptor- but also alpha-adrenoceptor-mediated modulation of thymopoiesis.

Age-associated plasticity of α1-adrenoceptor-mediated tuning of T-cell development.

Alpha(1)-adrenoceptors (α(1)-ARs) are involved in neuro-thymic and thymic intercellular communications, and consequently modulation of T-cell development. Ageing is associated with a number of changes in noradrenergic neuro-effector transmission, and possibly intercellular noradrenaline (NA)-mediated communication resulting in altered responses of target cells to NA. Thus, in old animals an altered NA modulation of thymopoiesis via α(1)-ARs may be expected. To test this hypothesis, in old and young adult Wistar rats we examined: 1) thymic NA levels, density of noradrenergic innervation and NA synthesizing cells, as well as α(1)-AR expression, and 2) then the effects of 14-day-long treatment with the α(1)-AR blocker, urapidil, on thymocyte development. Overall, the first part of study suggested augmented NA signalling to thymic cells via α(1)-ARs due to increased NA availability and α(1)-AR thymocyte surface density in old rats. The second part of study supported this assumption. Namely, although in rats of both ages urapidil affected the same thymocyte developmental steps ultimately leading to changes in the relative number of the most mature single positive TCRαß(high) thymocytes, its effects were generally more prominent in old animals. Following urapidil treatment, the percentages of CD4+CD8- cells, including those showing a regulatory CD4+CD25+RT6.1- phenotype, were increased, while CD4-CD8+ cells decreased. In old rats, an augmented thymic escape of immature CD4+CD8+ cells was also registered. In rats of both ages the thymic changes were accompanied by alterations in the proportions of major cell populations in the T-lymphocyte compartment of both peripheral blood and spleen, leading to an increase in the CD4+/CD8+ T-cell ratio. These alterations were also more pronounced in old rats. Moreover, in old rats following urapidil treatment the proportion of TCRαß+cells in the periphery was slightly greater reflecting, most likely, partly enhanced thymic production of regulatory CD161+TCRαß+cells. Thus, the study indirectly suggests an age-associated increase in the basal α(1)-AR-mediated inhibitory influence of NA on thymopoiesis.

Expression of alpha1-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis.

The study was undertaken to explore: i) the presence of alpha(1)-adrenoceptors (AR) on thymic lymphoid and non-lymphoid cells and ii) their putative role in T-cell development. The expression of alpha(1)-AR on thymic cells was assessed using both immunohistochemistry and flow cytometric analyses, while their putative role in thymopoiesis was estimated by analyses of thymocyte proliferation and apoptosis, and major thymocyte subset distribution in adult rats subjected to 14-day-long treatment with the alpha(1)-AR blocker urapidil. The presence of alpha(1)-AR was demonstrated on both thymocytes (mainly less mature CD3(-) and CD3(low) cells) and thymic non-lymphoid cells (thymic epithelial cells and CD68-positive cells). Chronic treatment with urapidil increased the thymic weight and thymocyte number. The increase in thymocyte number might, at least partly, be related to an enhanced thymocyte proliferation. In addition, an altered thymocyte subset distribution was observed in these rats. The increase in the percentage of CD4+CD8+ double positive (DP) TCRalphabeta(-) thymocytes was accompanied by the reduction in that of CD4+CD8+ (DP) TCRalphabeta(low) cells, and divergent changes in the percentage of the most mature single positive (SP) TCRalphabeta(high) thymocytes. In urapidil-administered rats the percentage of CD4+CD8- SP TCRalphabeta(high) thymocytes was increased, while that of the CD4-CD8+ TCRalphabeta(high) was reduced, compared with controls. In addition, proportions of CD4+CD25+RT6.1- and CD161+TCRalphabeta+ regulatory cells were increased. Collectively, the results indicate that alpha(1)-AR are involved in complex network of neuro-thymic and intrathymic communications that provide fine tuning of both conventional effector and regulatory T-cell development.

[Comparison of clinical data, ultrasonography, mamography and histological findings obtained by ex tempore biopsy for breast cancer diagnosis].

Breast cancer is really one from tumor with highest mortality in this country as well as in the word. For early detection of the loco-regional breast cancer and disease confirmation, many diagnostic procedures were recommended with aims to help in decision for surgery treatment. This comparative study reported data by clinical analyses, ultra-sonography, mammography and histological findings obtained after ex tempore biopsy, in 59 women with breast cancer aged from 16 to 69. The highest incidence of cancer was obtained in women over 61 years of age, although high rate of breast cancer was found in aging between 21 to 50 years. The fibroadenoma were founded in 40.68%, while malignant carcinoma ductale in 13.55% of all cases. Correlation between applied analyses for fibroadenoma was found in 86.05% cases, while in malignant lesions this percentage was highest (93.33%). Apart of these methods applied for early diagnosis in general hospital and obtained statistical significance in diagnosis, new techniques based on molecular level (hormone receptor status) must be used.

Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats.

The role of gonadal hormones in induction and, particularly, maintenance/progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized (Cx) rats were greater than in age-matched control rats, sham Cx (Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate (the proportion of proliferating cells was 18.6 +/- 0.7% in 2-month-old Cx (N = 5) vs 13.4 +/- 0.3% (N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals (apoptotic thymocytes were 9.8 +/- 0.9% in 2-month-old Cx (N = 5) vs 15.5 +/- 0.3% (N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture (72.6 +/- 1.2% in 10-month-old vs 9.8 +/- 0.9% in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli (14.1 +/- 0.2% in 10-month-old vs 18.6 +/- 0.7% in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.

[Myeloproliferative diseases as causative agents of portal and hepatic veins thrombosis].

Thrombosis of portal and hepatic veins is one of the most severe complications and most important causes of death of patients with chronic myeloproliferative diseases. Based on results of the past studies, myeloproliferative diseases were the causes of hepatic veins thrombosis in 30% and portal vein thrombosis in 20% of patients. The study presented 4 patients with myeloproliferative diseases complicated by thrombosis of splanchnic veins, aiming at the illustration of issue complexity in diagnostics and therapy. Two patients with portal vein thrombosis and recurring hemorrhage from esophageal varicosity were described. The first case was planned for shunting, while another case sustained bleeding on what account his anticoagulant therapy was discontinued, but it caused mesenterial thrombosis resulting in lethal outcome. Another two patients had hepatic veins thrombosis. Due to frequent, life-threatening bleeding from the esophageal and gastric varices, a patient with chronic Budd-Chiari syndrome and lineal vein thrombosis underwent mesocaval shunting. An immediate postoperative period was manifested by multiple thrombosis and hemorrhages that ended in his death. A patient with the acute Budd-Chiari syndrome was administered myelosuppressants and anticoagulants on time so reperfusion was restored. In myeloproliferative diseases, thrombosis of portal and hepatic veins gives rise to excessive portal hypertension with profuse hemorrhage from the esophageal and gastric varicosity which is difficult to manage because of complex coagulation disorders.

[Hepatopulmonary syndrome in liver cirrhosis]. / Hepatopulmonalni sindrom u cirozi jetre.

UNLABELLED: Hepatopulmonary syndrome (HPS) is defined by liver disease, hypoxaemia, increase of alveolar-arterial gradient, when inhaling room air, and intrapulmonary vascular dilatation. Pathoanatomical substrate of intrapulmonary vascular dilatation consists of dilated precapillary network, direct arterio-venous communication and dilated pleural blood vessels, "pleural spiders" [2]. Recently, hepatopulmonary syndrome gained clinical significance. Deterioration of arterial oxygenation in patients with liver disease indicates a very poor prognosis, because of which there are suggestions to classify hepatopulmonary syndrome as a new indication of liver transplantation [4]. AIM OF THE STUDY: The aim of the study was to examine the clinical and pathogenetic significance of intrapulmonary shunts in the development of respiratory disorders, and determination of correlation between intrapulmonary shunts and clinical, biochemical parameters in patients with liver cirrhosis. METHOD: In a prospective study over the period 1996-1999, we observed 50 patients with liver cirrhosis who were examined and treated at the Department of Gastroenterology and Hepatology of the Clinical Centre of Serbia in Belgrade. Hepatic examinations were based on medical history, physical examination, laboratory tests, ultrasound, duplex Doppler ultrasound, and histopathological findings. Hepatic failure was classified into 3 stages according to Child's classification. In this study we used 2 groups of pulmonary functional tests: analysis of arterial blood gas exchange and ventilation tests (spirometry, flow-volume curve and body pletismography). Arterial blood gas analysis was performed in supine and sitting positions while inhaling room air and after 15 min of inhaling hyperoxic mixture. RESULTS: Patients were classified according to the generally accepted Child's classification into 3 stages: Sixteen patients (32%) were in Child's A stage, 20 patients (40%) in Child's B stage, and 14 (28%) in stage Child's C. HPS was diagnosed in 9 (18%) patients with liver cirrhosis. The majority of patients with HPS (6) were in Child's C stage, while the other 3 patients were in Child's B stage. Biochemical parameters were considerably worse in patients with shunts in comparison to those without shunts. However, t-test shoved no significant difference. Hypoxaemia caused by intrapulmonary arterio-venous shunt in supine position was found in 7 (14%) patients. Mean value of PaO2 was 8.72 kPa (SD = 1.02). Hypoxaemia caused by arterio-venous shunt in sitting position was found in 9 (18%) patients. The mean PaO2 value was 7.41 kPa, SD = 1.81. Orthodeoxia was confirmed in all patients with intrapulmonary shunt. Hypoxaemia without shunt in supine position was found in 18 (36%) patients, while 12 (24%) patients had hypoxaemia without shunt in sitting position. Comparing groups of patients with shunt and without shunt in supine position, we found a borderline statistically significant difference in PaO2 values (p = 0.057, t-test). In sitting position the difference in PaO2 values between these groups was statistically very significant (p = 0.001, t-test). DISCUSSION: It is supposed that approximately 50% of patients with indication for liver transplantation have some form of arterial oxygenation disorder and 13-47% of these patients may have HPS [6, 7]. In our study, HPS was diagnosed in 18% of patients. We explain this high incidence by the fact that our study included the patients with advanced liver cirrhosis (stages Child's B and C). In studies performed up to date, there was neither correlation between biochemical liver function parameters and intrapulmonary shunts, nor any strong relation between severity of hepatic failure and degree of hypoxaemia [12, 13]. We noticed no correlation between hepatic functions (synthetic, excretory, transaminases) and PaO2 and/or intrapulmonary shunts. Some authors suggested that ventilation-perfusion disorder (Va/Q) is an important cause of hypoxaemia in

[Doppler-duplex ultrasonography in the diagnosis of cavernous portal vein]. / Ultrasonografija dupleks-dopler u dijagnostici kavernozne vene porte.

UNLABELLED: Prehepatic portal hypertension caused by cavernous transformation of the portal vein has been more and more considered as a multiorgan disease with circulatory changes in numerous organs related to systemic and splanchnic vascular network [1]. Honeycomb-like, spongy, cavernous portal vein is a rare clinical and pathoanatomical entity which usually results from portal vein thrombosis. Recanalization and neovascularization processes lead to cavernomatous transformation of the portal vein lumen and formation of periportal collateral hepatopetal venous varices (Petren's veins) [5, 6]. Recently, with Doppler ultrasonography and angiography cavernous portal vein has been identified as the cause of prehepatic portal hypertension. Usage of color Doppler and duplex Doppler ultrasonography has greatly contributed to diagnostic efficiency, while therapeutically, the disease remains a serious and controversial problem. METHODS: At the Institute of Digestive Diseases, Clinical Centre of Serbia, 8 patients with cavernous portal vein were studied in the period 1995-1997. Real-time duplex and color Doppler ultrasonography (Toshiba-SSA 100A with sector duplex probe 3.75 MHz, and 9 ATL with color Doppler convex duplex probe 3.5 MHz) were used. Indirect (arterial) portography was used for imaging of lienoportal system in the venous phase of angiography as follows: catheterization (Seldinger's technique) of the coeliac trunk or lienal artery, and catheterization of the superior mesenteric artery. Indirect portography was performed by injection of 60-80 ml of the contrast medium by an automatic pump, at 10-14 ml/sec, i.e. 8-10 ml/sec by the digital technique [7]. Peroral fiberendoscopy was performed in all patients by Olympus GIF-XQ 10 endoscope. RESULTS: In our study the conventional ultrasonographic examination failed to provide an appropriate image of the normal portal vein. In hepatoduodenal ligament multiple tubular and round structures were seen, revealing an atypical honeycomb or spongycavernous shape of the venous lumen (Figs. 1 and 2). Doppler ultrasonography of the lumen of these venous collateral structures revealed a continuous, hypokinetic flow, mid-rate 7.4 cm/sec, which was always hepatopetally directed (to the liver). Color Doppler ultrasonography detected extensive portosystemic collateralls in all patients, and varices in the gallbladder wall in 1 patient. The results of indirect portography correlated well with Doppler ultrasonographic findings. In all patients hepatopetal flow was found (Figs. 3 and 4). The aetiology was diverse: idiopathic, liver cirrhosis, haematological diseases, Crohn's disease and Marfan's syndrome. Two patients had IV degree varices in the distal third of the oesophagus, and 4 patients had II/III degree varices. Patients with posthepatic liver cirrhosis and Crohn's disease had no varices in the distal third of the oesophagus and gastric fornix. DISCUSSION: Since Pick (1909) described this malformation as the hepatopetal collateral, the haemodynamic concept of this entity has not been changed. Doppler ultrasonography and angiography confirm that the blood flow in cavernomas is hepatopetal, i.e. compensated and functional. Cavernous transformation of the portal vein is clinically manifested by bleeding from oesophagogastric varices. Haemathemesis is the most alarming complication and may be the first clinical sign. The haemorrhage is usually recurrent and profuse, but in most cases it is tolerated well owing to preserved hepatic function in patients without liver cirrhosis [19]. Portosystemic collateral circulation may take place via retroperitoneal and other spontaneous venous shunts, not involving the left gastric vein or vv. gastricae breves, when oesophagogastric varices are absent (our patient with Crohn's disease and posthepatitic B cirrhosis). Splenomegaly with hypersplenism is always present with cavernous transformation of the portal vein, and usually precedes the occurrence of gastrointestinal hae