Analysis of paraoxonase activity and lipid profile in lupus patients

INTRODUCTION: Immune-inflammatory processes play important role in the pathogenesis of atherosclerosis. Therefore, increasing attention is focused on rheumatic diseases with chronic inflammation, such as systemic lupus erythematosus. Besides direct influences, inflammation may modify the development of atherosclerosis by other mechanisms. AIMS: To examine paraaoxonase activity and lipid profile in lupus patients. METHODS: Authors entered 37 definitive lupus patients and 30 age- and sex-matched normal controls into the present study. Patients' age was 40.8 +/- 13.9 year, follow-up time 6.7 +/- 6.2 year, disease activity index 2.8 +/- 3.4. Lipid parameters (total cholesterol, LDL-C, HDL-C, Apo-AI and ApoB) were determined by an autoanalyser, paraoxonase and arylesterase activities were measured spectrophotometrically. Phenotypic distribution of the enzyme was determined by dual substrate method. Anti-oxLDL was measured by ELISA method, CRP by automatised immunoassay. Statistical analysis was performed by SPSS program. RESULTS: Despite of long disease duration and low inflammatory activity authors found significantly (p < 0.001) decreased paraoxonase activity (121.9 +/- 65.9 U/mL) (p < 0.001) in lupus as compared to control (188.1 +/- 78.9 U/mL), which correlated with the presence of atherothrombotic complications (p = 0.009). High activity BB phenotype did not occur in lupus. Lipid parameters and arylesterase activity were within normal range in both groups. No significant correlation was found between paraoxonase activity and disease activity index, dose of corticosteroid therapy, CRP and anti-oxLDL level. Arylesterase activity did not differ in lupus and control groups. CONCLUSIONS: Present results suggest that other mechanisms, e.g. antibodies, genetic factors, alteration in the distribution of HDL-subfractions or ensyme abnormalities in HDL remodelling may stand at the background of reduced paraoxonase activity in lupus.     

Hypercalcemia in neoplastic and granulomatous diseases: pathogenesis and treatment options

Hypercalcemia is a frequently observed laboratory phenomenon in clinical practice. It can occur in several diseases, among which it is associated most frequently with neoplasms, hyperparathyroidism and disorders of vitamin D metabolism. The appearance of hypercalcemia in neoplastic diseases is related to a poor prognosis in general. In most cases, malignant hypercalcemia is related to the secretion of parathormone-related protein, but other causes have also been described. Granulomatous diseases are associated with the hypersecretion of vitamin D metabolites. Fluid volume repletion, forced diuresis can be regarded as cornerstones in the therapy of acute hypercalcemia independent of its etiology, in addition, medications including bisphosphonates, calcitonin, gallium nitrate and glucocorticoids can be applied. In this review article, the authors present a brief synopsis of the pathogenesis of hypercalcemia associated with neoplastic and granulomatous diseases along with the treatment options, underlining the practical aspects.     

Improved outcome with sirolimus-cyclosporine regimen in high-risk renal transplant recipients

AIM: The immunosuppressive agents have a broad spectrum of adverse effects. In the absence of selective and specific drugs the decrease incidence and severity of side effects can be achieved by the combination of synergistic drugs only. Without wise selection and use of the combination of the potent immunosuppressive agents for the immunosuppressive maintenance therapy better results cannot be achieved without or fewer toxicities particularly in high-risk patients who lose their grafts prematurely. Therefore, a good combination will allow not only to reduce individual immunosuppressive drug induced toxicities but will also allow to achieve better graft and patient survival. MATERIAL AND METHODS: To assess the 6-year impact of a sirolimus-based regimen with, modest exposures to cyclosporine among three ethnic groups with different rejection risk, the authors performed a retrospective analysis of 470 renal transplant recipients who were treated contemporaneously: Group 1, high risk African Americans (n = 122); Group 2, moderate risk Hispanics (n = 132); Group 3, mild risk Caucasians (n = 216). Multivariate models were used to compare the outcomes in Group 1 with those of the other two groups. RESULTS: The cumulative incidence of acute rejection episodes over the entire follow-up period was similar among the groups: Group 1, 22.0%, Group 2, 24.2% and Group 3, 23.0%. Although there were no significant differences in overall or individual infection rates, Group 1 and 2 recipients displayed a significantly lower incidence of diarrhea at all times during follow-up compared with Group 3. All recipients showed similar rates of lymphocele formation. However, Group 1 displayed a reduced incidence and decreased severity of hypertriglyceridemia than Group 2 or Group 3 (89.3% vs. 97.2% vs. 93.2%), a similar incidence of hypercholesteremia (94.3% vs. 97.2% vs. 98.5%) was observed. The occurrence of post-transplant diabetes mellitus was greater in Group 1. than Group 3. but similar to Group 2. CONCLUSIONS: A concentration-controlled sirolimus-cyclosporine-prednisone regimen (with steroid withdrawal by 3 months) reduced the incidence of acute rejection episodes and increased 6-year graft survivals among high-risk African Americans to rates similar to other ethnic groups without an augmented toxicity profile.     

Results of photorefractive keratectomy in myopia with flying spot excimer laser with high speed and small beam diameter

PURPOSE: To examine the result of photorefractive keratectomy (PRK) with the next generation of flying spot excimer laser for the treatment of myopic refractive errors. PATIENTS AND METHODS: During the study 164 eyes of 98 patients were assessed. The average age was 29.4 +/- 4.62 years. The myopic eyes were divided into 3 groups: in Group 1. (n = 115 eyes) the eyes between -1.0 D and -6.0 D were evaluated, in this group the preoperative average refraction was -3.43 +/- 1.2 D (SE = spherical equivalent); in Group 2. (n = 31 eyes) the eyes between -6.1 D and -9.0 D were evaluated; the preoperative average refraction was -7.26 +/- 2.4 D (SE). In Group 3. (n = 18 eyes) eyes above -9.0 D were examined; in Group 3. the average preoperative refraction was -10.22 +/- 3.4 D (SE) Follow-up is 6 months. PRK treatments were carried out with the Zeiss Meditec MEL 80 G-Scan flying spot excimer laser, which was operated with a 0.7 mm beam diameter and 250 Hz frequency. RESULTS: In Group 1. The preoperative correction decreased to -0.14 D (SE); in 71% of the treated eyes uncorrected visual acuity (UCVA) was 1.0; in 24% of the eyes UCVA improved to 1.2. Best corrected visual acuity (BCVA) was unchanged in 65% of the eyes; while in 34 improved (in 24% it improved by more than 2) Snellen lines. In Group 2. the preoperative correction decreased to -0.13 +/- 0.01 D (SE); 67% had 1.0 and 8% had a 1.2 UCVA. BCVA was unchanged in 92% in Group 2.; in 8% BCVA increased by 1 or 2 Snellen lines. In Group 3., the preoperative correction decreased to -0.44 +/- 0.2 D (SE); 96% of the eyes had a 0.8 UCVA; BCVA did not change in 75% of the eyes, 25% of the eyes gained 1 Snellen line. CONCLUSIONS: Myopic PRK treatments with the 3rd generation of excimer laser were effective and safe. Regarding BCVA, best results were obtained in the low and medium myopia groups.     

Microscopic colitis

AIM: Various case presentations in the literature discussed that frequent watery diarrheas introduce the clinical picture of microscopic colitis and intermittent or continuous diarrhea can remain. On the other hand, numerous cases never suffered from episodes of diarrhea but suffered from chronic constipation definitely. The authors present their first observations in Hungary. METHODS: A cohort of patients with independently confirmed typical histopathological changes was investigated. 53 patients with histologically proved MC (46 with CC, 7 with LC) were included. The existence of diarrhea or constipation and the co-existence of autoimmune diseases also investigated and all data were retrospectively analyzed. RESULTS: In contrast of the literature, about half of the patients had chronic constipation and cca. 50% of MC patients had autoimmune disease and the diagnosis of autoimmune disease was always prior to MC. CONCLUSIONS: Causes of inducing and amplifying the processes of "remodelling" the gut wall are thought to be unknown, but the results are: altered structure (and function?). All useful observations of this study may enrich the practice and can help these patients.     

Atypical glandular cells (AGC) on Papanicolaou smears--the great challenge of cervix screening programs

The "grey zone" diagnostic category for glandular cells in the Bethesda System 2001 (TBS 2001) has undergone significant modification since its last version in 1991. PATIENTS: The aim of the study was to follow up patients with "atypical glandular cells of undetermined significance" (AGUS)/ "atypical glandular cells" (AGC), and adenocarcinoma cytological interpretation, based on a three-year material between 2000-2002 at the Department of Cytopathology of National Institute of Oncology, Hungary. The smears were reviewed and interpreted according to TBS 2001. Histological slides were reviewed and cytohistologic correlations were investigated. RESULTS: Out of 36193 conventional Papanicolaou smears, there were 276 AGC-NOS (AGUS, favour reactive in TBS1991) and 7 AGC-favour neoplastic (AGUS, favour neoplastic in TBS 1991) (altogether 0.78%) and 35 (0.1%) adenocarcinoma interpretations. Histology was available in 136 (AGC-NOS: 106, AGC-favour neoplastic: 7 and adenocarcinoma: 23) cases. Among the followed 106 patients with AGC-NOS, there were 24 cases with concurrent "grey zone" squamous, ASC-US, interpretation. Clinically significant lesions were found in 5/7 (71%) of cases of the AGC-favour neoplastic group, and in 27/106 (25%) of the all AGC-NOS group, the difference is statistically significant. This ratio is 16/82 (20%) in the AGC-NOS only cases, while 11/24 (46%), in the AGC-NOS with concurrent ASC-US cases, the difference is statistically significant. The high-grade lesions were mostly squamous. CONCLUSION: The results suggest that AGC-NOS with concurrent ASC-US interpretation represent a group of potential patients with statistically significant higher risk of clinically significant (among them high-grade) lesions.     

Hybridization and their application in the DNA array technology

Hybridization and their application in the DNA array technology. DNA hybridization arrays measure simultaneously the expression of several genes. First, a known DNA sequence (probe) is fixed on a firm basis. Then the complementer sequence (target sequence) is linked to it during the hybridization process. The target sequence extracted from biological samples is fluorescently, enzimatically or radioactively labeled before detection. Higher expression results in higher signal in the detection system. Unlabeled DNA strands can also be detected, as the electronic and optical characteristics of the DNA is altered after complementer hybridization. In this review we summarize the basics of hybridisation and its newest application area in the DNA array systems.     

Genotype-phenotype associations in inflammatory bowel disease

Inflammatory bowel disease has traditionally been categorized as either ulcerative colitis or Crohn's disease on the basis of clinical, radiological and histological criteria. Emerging data suggest that inflammatory bowel disease comprises a heterogenous family of inflammatory disorders in which the specific clinical manifestations of disease are determined by the interaction of genetic and environmental factors. Interactions of susceptibility and modifying genes influence the specific features of disease phenotype, penetrance, location, behavior, and complication. CARD15/NOD2 mutations are significantly associated with ileal location, whereas certain HLA haplotypes are associated with colonic disease. The associations with CARD15/ND2 mutations and early age at onset, as well as disease behavior (stricturing, fistulizing type) are less consistent. Distinct HLA alleles contribute to the occurrence of extraintestinal manifestation. With the increasing number of genotype-phenotype relationship, it is hoped that a molecular classification can be created, in which various disease subtypes are categorized according to their specific genotypes. In the future, such sheme may permit early, accurate diagnosis, prediction of disease course, complications, prognosis, as well as treatment response.