Corelation of lymphocytic infiltrates with the prognosis of recurrent colo-rectal cancer.

BACKGROUND: Recent studies are focusing on complementary prognostic and predictive markers that could complete the predictive TNM staging and one of the most promising directions is the study of tumor immune infiltrates. MATERIALS AND METHODS: Our 2-year retrospective study includes resection specimens from the primary tumors of 23 patients presenting to our clinic for a local or a distant relapse after colon or rectal cancer. From every primary tumor specimen we obtained immunohistochemically stained slides in order to assess cd3, cd4, cd8, cd45ro and cd68 infiltrates. Digital analysis assessed the density and percentage of positively stained cells in the normal peritumoral tissue, invasive margin and center of the tumor. RESULTS: A small density of cd8 positive cells in the peritumoral region was strongly correlated with a longer disease-free interval (p=0.009) and the Kaplan-Meier survival analysis showed that the percentage of cd8+ T cells could be used to stratify patients in terms of relapse risk (p=0.006). We found no correlation between invasion front infiltrates and intra tumoral infiltrates and the disease-free interval. CONCLUSION: Our study concludes that cytotoxic T-cell infiltrates in the normal peritumoral tissue could be used to predict a more aggressive tumor in terms of the relapse risk.

Morphometric study of aortic wall parameters evolution in newborn and child.

The largest artery in the human body, intimately connected to the heart, aorta is usually regarded as the major source of oxygenated blood for the circulatory system. The three concentric layers, which surround the aortic lumen-the tunics intima, media and adventitia, transform the aorta in a large elastic duct, which is irregular calibrated according to its segments. The special aortic distensibility is facilitated by its elastic circumferential lamellar complex. Any disturbance of its structural components is able to interfere with its normal and vital activity. Our study intends to reveal that the development of elastic lamellae should be regarded not only as an indispensable step for the aortic wall configuration, but also like a process in a firm connection with the rest of aortic wall components. The transition from intrauterine life to a new stage of life, childhood, has to determine an adequate adaptation of almost all the components of aortic wall, in order to sustain a consistent pulsatile blood flow. Stereological quantitative analysis of thoracic aortic fragments prelevated from newborns and children was performed in order to estimate the dynamic of vascular wall increase. We first estimated the general configuration of the thoracic aortic wall, quantifying the principal constituents; the connective tissue profile, investigated through its main elements, collagen and elastic fibers, supports the idea that each type of fiber has a distinct evolution in different groups of ages and has to be correlated with their involvement in maintaining of the aortic wall mechanical properties. Elastic fibers percentage volume was increased in both examined groups, with a small difference reported in children aorta, while collagen fibers exhibit a slow increase in children aorta. Our morphometric quantitative assessment suggests that further studies have to draw of in a precisely manner the outline of the secretory well defined function of vascular smooth muscle cells; the elucidation of the manner in which the secretory pathway for each type of fiber becomes fully adapted to every stage of aortic development will allow a new perspective in aortic pathology.

The relevance of circadian rhythms disruption on pulmonary SOD expression in rat.

The light-dark cycle represents a significant component of the circadian system in most mammals. Any disturbance of this cycle is reflected in a large number of changes in the physiological and also behavioral status of the organism, together with considerable alterations of the redox balance. Increasing evidence suggests that reactive oxygen species (ROS) have their own function in the circadian system. Superoxide dismutases (SOD) family represents the first prompt antioxidant enzymatic system, identified in all aerobic organisms and able to counteract ROS toxicity; there are three distinct isoenzymes: CuZn-SOD (SOD1), Mn-SOD (SOD2), and extracellular EC-SOD (SOD3). In the case of circadian disruption, when ROS production is enhanced, the impact of the oxidative aggression on superoxide dismutases (SOD) rhythmicity and distribution is still unclear. To estimate the influence of circadian rhythms disruption on pulmonary SOD, we exposed male Wistar rats to continuous light stimuli for four weeks and then investigated the SOD immunohistochemical expression in lungs, which are among the most sensitive organs to oxygen. CuZn-SOD, Mn-SOD and EC-SOD presented a particular immunoreactivity in the investigated pulmonary tissues. These findings support our viewpoint that there is a direct correlation between the rhythmicity of circadian cycles and pulmonary SOD expression.

Oxidants and antioxidants relevance in rats' pulmonary induced oxidative stress.

INTRODUCTION: Even if the reactive oxygen species were discovered, described and detailed a long time ago, there is still little data about the mechanisms of oxidative stress, their tissular effects and about an efficient antioxidant strategy, involving animal experimental models. It has been shown that the lung is one of the most exposed organs to the oxidative stress. The particular effects of different types of oxidative stress on lungs were investigated in this experimental study, in order to quantify the intensity and the extent of the pulmonary damage, featuring the antioxidant enzymatic protective role. METHODS: The study of lung injury was performed on four distinct groups of Wistar rats: a control group versus a group exposed to continuous light deprivation versus a group exposed to nitrofurantoin versus a group exposed to continuous light deprivation, to nitrofurantoin and vitamin C. Pulmonary samples were taken and treated for microscopic analysis. A qualitative immunohistochemical estimation of pulmonary superoxide dismutase 1 (SOD 1) was performed. Blood tests were used in order to reveal the presence and intensity of oxidative stress. RESULTS: Continuous light deprivation and the chronic administration of nitrofurantoin acted as oxidants with a certain involvement in lung damage--vascular and alveolar wall disturbances. Adding an antioxidant, such as vitamin C, considerably improved lung reactivity to oxidative stress. CONCLUSION: The chronic exposure to oxidants in the induced oxidative stress sustains the development of specific lung alterations. SOD 1 positive reaction underlines the complex enzymatic defense in oxidative stress.

[Immunohistochemical evaluation of topoisomerase IIalpha as proliferation factor in gastric lymphoma]. / Evaluarea imunohistochimica a topoizomerazei IIalpha ca factor de proliferare in limfoamele gastrice.

UNLABELLED: Topoisomerase IIalpha is a nuclear enzyme essential for DNA replication, with presumed prognostic value in various tumors. MATERIAL AND METHODS: Study group included 34 gastric lymphomas. Tissue samples, formalin-fixed, paraffin-embedded, were investigated by immunhistochemistry using monoclonal antibodies anti Ki67 and anti topoisomerase IIalpha. RESULTS: The 34 gastric lymphomas were previously diagnosed as follows: 14 MALT lymphoma and 20 aggressive lymphoma (17 diffuse large B-cell lymphoma, 2 diffuse large B-cell lymphoma with minor MALT component and 1 peripheral T-cell lymphoma). Both markers (Ki67 and topoisomerase IIalpha) were positive in 2-31% of tumor cells in MALT lymphoma, while in aggressive lymphoma up to 46-98% of tumor cells showed a positive expression. CONCLUSION: Similar expression of Ki67 and topoisomerase IIalpha recommends the utilization of topoisomerase IIalpha in determining the proliferation fraction in gastric lymphomas. In addition, we suggest that it might be possible to use topoisomerase II inhibitor agents in high grade gastric lymphomas.

Adipokines involvement in lung function.

The last two decades brings many data about white adipose tissue capacity to secrete hormones, named adipokines, which could mediate the relationship between obesity and lung diseases. In this paper we presented some data about adipokines involvement on pulmonary function, with special emphasis on leptin, adiponectin, tumor necrosis factor alpha, vascular endothelial growth factor, resistin, hepatocyte growth factor, interleukin-6, angiotensinogen and apelin.

HLA-A and -B phenotypes associated with tuberculosis in population from north-eastern Romania.

UNLABELLED: HLA antigens are involved in inducing either susceptibility or resistance to different diseases. Many studies reported various associations between HLA antigens and tuberculosis, depending on race, ethnic group and geographic area. AIM: Our purpose was to identify HLA class I antigens inducing susceptibility to tuberculosis in population from North-Eastern Romania. PATIENTS AND METHODS: The study group consisted of 50 tuberculosis patients and the control group included 90 healthy people. HLA-A and HLA-B antigens were determined using the CDC-NIH (complement-dependent-cytotoxicity-National Institute of Health) assay. A comparison was made between the frequency of HLA antigens expression in the two studied groups. RESULTS: HLA-B18 and HLA-A29(19) were expressed more frequently in tuberculosis patients. The difference was statistically significant only for HLA-B18 antigen. HLA-B7 and -B61(40) antigens were expressed with statistically significant higher frequency in controls compared to tuberculosis patients. The frequency of other HLA-A and HLA-B antigens was either comparable in the two groups or without statistical significance. CONCLUSIONS We found a positive association between HLA-B18 antigen and tuberculosis, while HLA-B7 and HLA-B61(40) antigens seem to protect against the disease.

[Maternal immunophenotypic profile in normal pregnancy and preterm birth]. / Profilul imunofenotipic matern în sarcina normala si nasterea prematura.

UNLABELLED: During normal pregnancy, the maternal immune response achieves a split tolerance state towards the fetal allograft, expressed by immunophenotypic profile. This may be impaired in the preterm birth. Our study aimed to analyze the immunophenotypic profiles of the peripheral and retroplacental blood in women with normal pregnancy and preterm birth. Blood leukocyte populations were assessed by flowcytometry in nine normal at term pregnancies, five preterm births and eight nonpregnant controls. Our results showed in normal pregnant women as compared to controls, a significant decreased number of lymphocytes, monocytes and B cells, while granulocytes, T-lymphocytes and the T CD8+ subsets were elevated. The CD4/CD8 ratio was significantly decreased, especially in the retroplacental blood. The preterm birth group demonstrated a significantly elevated number of lymphocytes and B cells, lower T CD8+ cells and an increased CD4/CD8 ratio, in comparison with normal pregnancies group. CONCLUSION: Normal pregnancy determines a suppressive immunophenotypic profile that is impaired in the preterm birth suggesting its immunological involvement.

HLA-B57 is significantly associated with psoriasis in Northeast Romania [corrected].

UNLABELLED: The aim of the study was to identify HLA class I types associated with susceptibility to psoriasis among population of Northeast region of Romania. PATIENTS AND METHODS: 27 psoriatic patients and 89 controls were typed serologically for HLA-A and HLA-B lymphocyte expression using CDC-NIH (complement dependent-cytotoxicity--National Institute of Health) method. The Terasaki plates used for HLA class I typing were prepared in our laboratory using antisera of known specificities. RESULTS AND CONCLUSIONS: psoriatic patients in the group of study frequently express HLA-B57 phenotype. The relative risk induced by this phenotype was highly statistically significant (p = 0.0016) while HLA-B13 was not associated with a significant risk for developing psoriasis in patients under study compared with controls (p = 0.48). Also, HLA-B27 (p = 0.96) and HLA-B44 (p = 0.99), reported by others to be associated with late psoriasis, do not meet (a particular) disease susceptibility between psoriatic patients under investigation.

[Synchronous colonic cancers]. / Cancerele sincrone ale colonului.

UNLABELLED: The aim of this study is to present the difficulty of an accurate preoperative diagnostic for synchronous colonic cancers and to sustain the necessity of total colectomy. A retrospective study was carried out on 16 patients hospitalized in the IIIrd Surgical Unit, St. Spiridon Hospital, U.M.Ph. "Gr.T.Popa" Iasi between 1990-1999. The surgical procedures were: extensive colectomy with ileo-sigmoid anastomosis, segmentary colectomy, total colectomy with ileo-rectal anastomosis. RESULTS: Perioperative mortality: zero; uneventfully recovery for all patients. A metachronous lesion 3 years after the first operation was detected in one patient; postoperatively, one patient developed occlussion 3 months after, requiring re-operation. CONCLUSIONS: 1. synchronous colonic cancers are closely related with a genetic instability of the colonic mucosa; 2. total colectomy is a safe manner to prevent metachronous lesions.

[The evolution of the natural-killer-dependent cytotoxic activity during normal pregnancy]. / Dinamica citotoxicitatii natural--killer (NK) dependente în evolutia sarcinii fiziologice.

The fetus was compared to an allograft because paternal antigens are also expressed. Even the analogy is not a real one, the main steps of the rejection phenomenon are relevant for the understanding of the complex materno-fetal interactions as the large granular lymphocytes are the first immune cells which invade the graft. Due to the important role of NK cells in the cell mediated immune response, the purpose of this paper was to assess the NK cell dependent cytotoxicity during normal pregnancy. The study was performed on a test group of 52 normal gravidas, in the Ist, IInd and IIIrd trimester and a control group of 20 healthy nonpregnant women with similar age and parity averages. The cytotoxic activity of the NK cells was measured in a 51Cr release assay against K 562 cell line. The results were expressed as the cytotoxicity index (%) and showed a statistically significant decrease for all gravidas compared to controls, mostly for the IInd trimester. The trend of the NK cytotoxic activity during normal pregnancy suggests the deep involvement of the NK cells in the mechanisms acting at the fetomaternal interface.

Production of interleukin-10 and transforming growth factor beta by peripheral blood mononuclear cells in Q fever endocarditis.

The pathophysiology of Q fever endocarditis is characterized by the suppression of antigen-specific cell-mediated immune responses. We investigated the production of interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta), known to interfere with the development of protective cell immunity. IL-10 was markedly released by unstimulated peripheral blood mononuclear cells (PBMC) from patients with Q fever endocarditis. This release resulted from the upregulation of IL-10 gene transcription. Similarly, the release of TGF-beta1 and TGF-beta2 was significantly higher in patient PBMC than in control cells, but the expression of their respective mRNA was not enhanced in patient cells. In contrast, lipopolysaccharide-stimulated transcription and release of IL-10 and TGF-beta were similar in patients and controls. The release of IL-10 by PBMC but not that of TGF-beta was correlated with the clinical status of the patients. First, IL-10 production was correlated with specific antibody levels. Second, IL-10 release remained elevated in patients prone to relapse. Taken together, our results suggest that the release of IL-10 and TGF-beta is upregulated in Q fever endocarditis. IL-10 might be considered as a marker of disease relapses and might be instrumental in monitoring the efficiency of the treatment.

Upregulation of tumor necrosis factor alpha and interleukin-1 beta in Q fever endocarditis.

The occurrence of Q fever endocarditis likely involves some alterations in the responses of monocytes, the in vivo targets of Coxiella burnetii. To test this hypothesis, the production of the inflammatory cytokines tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 was assessed in monocytes from patients with Q fever endocarditis. Spontaneous transcription and secretion of tumor necrosis factor and interleukin-1 were significantly higher in patient monocytes than in healthy controls. The interleukin-6 transcripts were also upregulated in patient cells. Moreover, in patients with recent endocarditis exhibiting high titers of immunoglobulin G directed to C. burnetii in phase I, monocytes released significantly higher levels of tumor necrosis factor and interleukin-1 than in patients with stabilized endocarditis. Immunoglobulin G titers and the overproduction of tumor necrosis factor and interleukin-1 were significantly correlated. Hence, the overproduction of inflammatory cytokines might be a marker of disease activity.

[The value of laparoscopic cholecystectomy in the treatment of gallbladder pathologies]. / Valoarea colecistectomiei laparoscopice în tratamentul colecistopatiilor.

We have prospectively studied all cholecystectomies performed in one year in our clinic in two groups: 190 cases performed laparoscopically and 98 open. We used standardized records and the EPI 5 program on an IBM compatible computer. There were no significant differences between groups regarding weight, sex and proportion of cases with acute cholecystitis. There were however major differences regarding age, type of habitat, ASA score and association with acute pancreatitis, obstructive jaundice and angiocholitis. Conversion of laparoscopic cholecystectomy to open procedure was imposed in 17 cases (not included in statistical analysis) due to technical difficulties (12 cases), haemorrhagic accidents (6 cases), injury of the common bile duct (1 case), stones lost in the abdominal cavity (3 cases), local peritonitis (5 cases). Laparoscopic cholecystectomy lasted a mean of 74 minutes. We encountered 3 specific complications: one CBD injury recognized intraoperatively and managed by Kehr's procedure (one CBD injury in the open cholecystectomy group), one small bowel perforation and one of biloma. Mortality averaged 0.5% in the LC group (one case of late postoperative stroke considered not related to the procedure) and 1% in the open cholecystectomy group. The hospital admission period was significantly reduced in the LC group (5 days vs. 12 days). LC appears as a safe procedure with a low complication rate. Conversion to open procedure is not a complication. Our study recommend LC as the method of choice in the treatment of gallbladder lithiasis.

[The parameters of the immune function in the evolution of HIV-1 infection in institutionalized children in Romania]. / Parametri ai functiei imune în evolutia infectiei HIV1 la copii institutionalizati din România.

OBJECTIVE: To describe the evolution of HIV-1 + horizontal infected children nursed in closed community. METHOD: The biological status of 26 HIV-1 + children nursed in Iasi Orphanage was assessed in dynamic during April. 1993-Feb. 1994. The income age ranged among 1 month-3 years. RESULTS: The following progressive stages could be drawn accordingly to the biological status parameters dynamic: stage 1 ("oligosymptomatic"), stage 2 ("multiform, medium or severe symptomatology"), and stage 3 ("severe immunodepression, with predominant infectious symptomatology, waves evolution"). These stages could not be assimilated to the currently CDC or WHO classifications. The following thresholds of the immunologically parameters separate the stages 1 and 2, and respective stages 2 and 3: CD4% lymphocytes (27% respective 20%); absolute CD4+ lymphocytes (1150/microliter respective 700 + 750/microliter), CD4/CD8 ratio (0.75 respective 0.45), beta 2-microglobulin (1.5 mg/1000 respective 2.5 mg/ 1000). Lymphocytes lacking the markers CD4, CD8, CD19, CD3, ranging between 15 + 20% were also detected by flow-cytometry; these cells could be attributed to the immature subpopulations (typically for dystrophy) or to down-regulation of membrane expression of some markers. Also, a dichotomy in the distribution of the CD2/CD3 surface markers was recorded in the case of lymphocytes. CONCLUSIONS: Immunological features demarcate this epidemiological group versus the current described models for the HIV-1 + child.

[The Shouldice procedure in the surgical treatment of inguinal hernias]. / Procedeul Shouldice în tratamentul chirurgical al herniilor inghinale.

The Shouldice repair gained a major importance in the treatment of inghinal hernias provided by the excellent results that had been obtained in the Shouldice Hospital on more than 200,000 cases. This study analyze prospectively 101 cases of inguinal hernias that had been treated using the Shouldice procedure with in a 3 year period, comparative with a control cohort of 102 cases of inguinal hernias treated using classic procedures (Bassini, Kimbarowski). The data analyze was performed using Kruskal-Wallis H test and t Student test. The immediately postoperative results have been favorable in 95% cases and the long term postoperative results have been very good in 99% cases (a unique recurrence in a multiple recidivated patient). The result of this study proves that Shouldice repair has advantages comparative with classic treatment: short postoperative hospitalization, low incidence of complication and recurrence.

[Malignant tumors of the digestive tract below the diaphragm in young people]. / Tumori maligne ale tubului digestiv subdiafragmatic la tineri.

We have retrospectively studied 1243 malignancies of the infradiaphragmatic tract treated in the First Surgical Clinic between 1978-1994 (678 gastric, 300 rectal and 256 colonic malignancies). Out of these 39 cases have been encountered in young patients (14 gastric, 13 colon and 12 rectal malignancies). The following particularities have been noted in this group: hereditary predisposition, more advanced stage at diagnosis, predominance of non-Hodgkin lymphomas and poorly differentiated forms. Young age does not significantly influence prognostic, with the control group. In young people the most important prognostic factors are tumor stage, cellular grading and tumor DNA index as determined by flow cytometry.

[The determination of the prevalence of antibodies to the hepatitis C virus (anti-HCV) and of the serum levels of C-reactive protein in chronic dialysis patients]. / Determinarea prevalentei anticorpilor fata de virusul hepatitei C (anti-VHC) si a nivelelor serice ale proteinei C reactive la pacienti dializati cronic.

UNLABELLED: The chronic dialysis patients are subject at risk for the hepatitis C virus (HCV) infection. Among these subjects, the hemodialysis-induced and increased synthesis of IL6 which suggest an acute phase response. 58 chronic dialysis patients were tested for presence of anti-HCV antibodies; 45 (77.58%) presented this serological marker. None of the 15 nursing subjects tested presented anti-HCV. C reactive protein (CRP) levels were measured in 41 patients. Elevated levels were detected in 5 (12.19%) patients. Such a high prevalence of anti-HCV reveals the hemodialysis to be a risk factor for the HCV infection. CRP levels measured by Mancini method lack the sensitivity for a more accurate interpretation. CONCLUSION: 1. the high anti-HCV prevalence among hemodialysis patients emphasize the opportunity of blood testing also for serological markers in ante-transfusional screening. 2. the immunoturbidimetry method for CRP testing may be a better assay in order to establish significant correlations.