Determinants of adrenal androgen hypofunction in premenopausal females with rheumatoid arthritis.

The aim of our study was to investigate adrenocortical function in the context of disease activity and inflammatory status in premenopausal RA females. Adrenal glucocorticoid and androgen responses to the 1 microg ACTH 1-24 test were investigated in 23 premenopausal RA and in 15 age- and BMI-matched healthy females. Twelve RA patients were on low-dose prednisone (<8.5 mg/day). Patients with DAS28>3.2 had lower (p<0.05) total plasma cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone and androstenedione responses in the ACTH test compared to healthy controls. Patients with DAS28>3.2 had lower (p<0.05) dehydroepiandrosterone response in the ACTH test compared to patients with DAS28

Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term.

Chronic inflammation and low-dose glucocorticoid effects on glucose metabolism in premenopausal females with rheumatoid arthritis free of conventional metabolic risk factors.

Chronic systemic inflammation is associated with increased cardiovascular mortality in patients with rheumatoid arthritis (RA). The aim of our study was to investigate association of glucose metabolism and inflammatory markers in a group of patients with rheumatoid arthritis free of other metabolic risk factors. Twenty-two premenopausal RA females (11 patients on low-dose GC (<8.5 mg/day of prednisone or equivalent), 11 patients without glucocorticoid therapy) and 15 age- and BMI-matched healthy females underwent the oral glucose tolerance test. The insulin sensitivity indices according Matsuda (ISI(MAT)) and Cederholm (ISI(CED)) as well as HOMA2 %S were calculated. Cytokines, lipid profile, non-esterified fatty acids (NEFA) and plasminogen activator inhibitor-1 (PAI-1) were measured in baseline blood samples. Despite elevated interleukin IL-6 and TNF alpha, glucose, insulin and C-peptide responses to oral glucose load as well as ISI(MAT), ISI(CED), PAI-1 and NEFA were comparable in both RA groups and healthy controls. HOMA2 %S correlated with disease activity. In conclusions, low-dose glucocorticoid treatment does not lead to glucose metabolism impairment in RA patients without other metabolic risk factors. Increased cardiovascular mortality and morbidity is probably due to a direct effect of systemic inflammation on myocardium and/or blood vessels.

Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.

Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300)

[Systemic lupus erythematodes]. / Systémový lupus erythematosus.

Systemic lupus erythematodes (SLE) is chronic autoimmune disease, characteristic by production of autoantibodies against different autoantigens. Etiopathogenesis in not precise determinated, but genetic, immunologic, hormonal factors or influence of environment are assumed. It manifests by various symptoms and it can affect whichever organ or system in the body. Clinical manifestation are due chronic inflammation in the tissues, which is caused first of all by deposit of immunocomplex and by cytotoxic damage. At the last decades the mortality of patients with SLE is markly lower and their live is prolong. In spite of this diagnostic, to follow up and therapy of this disease is complicated and it requires the colaboration of more branches of medicine.

Salivary interleukin-6 and tumor necrosis factor alpha in patients with drug-induced xerostomia.

It is well known that cytokines are involved in the homeostasis of oral cavity and that altered levels of either serum and/or salivary cytokines have been found in certain oral/systemic diseases. So far, cytokines in connection with xerostomia have been investigated in patients with Sjögren's syndrome. We wanted to find out whether drugs themselves influence salivary glands, which would result in altered cytokine level or whether xerostomia itself of different causes leads to the changes in salivary cytokine levels. Therefore, the aim of this study was to evaluate levels of salivary interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha in 30 patients with drug-induced xerostomia, age range 29-84 and mean 63.9 years. Control group consisted of 30 healthy participants, age range 30-82 years and mean age 65.2 years. Enzyme-linked immunoassay was performed on commercially available kits. Statistical analysis was performed by use of Student's test. No significant differences in salivary IL-6 and TNF-alpha between patients with drug-induced xerostomia when compared with the healthy controls were found (P < 0.05). We might conclude that drugs do not induce damage to the salivary glands which could be seen in altered salivary IL-6 and TNF-alpha levels and that xerostomia itself, induced by drugs does not alter levels of the investigated salivary cytokines.

Salivary interleukin-6 and tumor necrosis factor-alpha in patients with burning mouth syndrome.

Burning mouth syndrome (BMS) is characterized by burning symptoms on the clinically healthy oral mucosa. To date, etiology of BMS is still unknown. We hypothesized that maybe inflammation which is not clinically apparent might lead to burning symptoms which would then result in altered cytokine profile. In the 28 female patients with BMS (age range 48-80 years, mean 64.05 years) and 28 female controls (age range 40-75 years, mean 63.82 years) by use of enzyme-linked immunosorbent assay, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels were determined. Statistical analysis included use of independent sample t-test and P < 0.05 was considered as significant. Our results show no significant differences between patients and controls regarding salivary IL-6 and TNF-alpha.

Salivary interleukin-6 and tumor necrosis factor-alpha in patients with recurrent aphthous ulceration.

BACKGROUND: Recurrent apthous ulceration (RAU) is a well known oral disease which seems to be mediated principally by the immune system. However, it is still a matter of debate which part of the immune system is implicated in its pathogenesis as a reaction to the still unknown antigen. The aim of this study was to evaluate salivary cytokines, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha. METHODS: In 26 patients with minor RAU, age range of 23-49 years (mean 27.3 years), during both the acute phase and remission and in 26 healthy controls, age range of 22-64 years (mean 30.1 years), salivary IL-6 and TNF-alpha levels were determined by use of enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed by use of descriptive statistics. RESULTS: Significant differences in salivary TNF-alpha between healthy controls and patients with acute RAU and during the remission period were found (P < 0.001) as well as between patients with acute RAU and those during the remission period (P < 0.001). No differences in salivary IL-6 between all three groups could be found. CONCLUSIONS: We might conclude that elevated salivary TNF-alpha levels during acute RAU and especially during the remission period are of importance in RAU, whereas salivary IL-6 levels seem not to play a role in the RAU disease.

The significance of salivary interleukin 6 and tumor necrosis factor alpha in patients with oral leukoplakia.

It is well known that cytokines play an important role in oral diseases. Furthermore, increased levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) have been reported in patients with cancer and premalignant lesions such as oral lichen planus and oral submucous fibrosis. The aim of this study was to assess salivary IL-6 and TNF-alpha levels in 30 patients with histopathologically confirmed leukoplakia (age range 24-78, mean 52.3 years) in comparison to 34 controls (age range 27-79, mean 52 years). Salivary IL-6 and TNF-alpha were determined by enzyme linked immunoadsorbent assay. Statistical analysis was performed by use of Mann-Whitney test for independent samples and values lower than 0.05 were considered as significant (p<0.05). Significantly higher levels of salivary IL-6 and TNF-alpha in patients with oral leukoplakia when compared to healthy controls were found. The levels of salivary IL-6 and TNF-alpha did not correlate with the size of leukoplakia (lesions) nor with its localization regarding high and low risk sites for malignant transformation. Levels of salivary IL-6 and TNF-alpha were not influenced by smoking habits. We can conclude that increased salivary IL-6 and TNF-alpha might play a certain role in oral leukoplakia.

Pregnancy outcomes and deliveries following laparoscopic transsection of uterine vessels: a pilot study.

OBJECTIVE: To assess pregnancy outcomes and deliveries after laparoscopic uterine artery transsection (LTUV) in symptomatic women with fibroids. SETTING: Department of Obstetrics and Gynecology, Endoscopic Training Center, Baby Friendly Hospital, Kladno, Czech Republic. DESIGN: One hundred and fifty three patients underwent laparoscopic transsection of uterine vessels during a 4-year period. RESULTS: Nine of the 21 women desiring pregnancy conceived spontaneously and one after anovulation treatment. The average age of the women was 32.4 years, and the range was 26-39 years. Two women had vaginal delivery at term and one delivered vaginally at 31 weeks secondary to premature preterm rupture of membrane (PROM). Four others delivered at term by cesarean section. One woman with placenta previa was delivered by cesarean section 3 weeks before term. Mean birth weight was 3199 g (range 1710-3910 g). One spontaneous abortion was reported in the first trimester of pregnancy. One case of undesired pregnancy occurred. An extrauterine pregnancy was reported in this woman. CONCLUSION: LTUV is a minimally invasive operative procedure, that preserves the uterus and ovarian blood supply and allows for the achievement of pregnancy in women with symptomatic fibroids. Fetal growth and umbilical Doppler findings remained normal in all cases. An increased risk for preterm delivery and cesarean section was found in this small series.

Salivary and serum interleukin 6 and basic fibroblast growth factor levels in patients with oral squamous cell carcinoma.

AIM: A role of various cytokines has been implicated in the pathogenesis of many carcinomas, and albeit the role of interleukin 6 (IL-6) and basic fibroblast growth factor (bFGF) in sera has been studied in patients with oral carcinomas, data upon salivary IL-6 and bFGF are lacking. The aim of this study was to evaluate levels of IL-6 and bFGF in the saliva and serum of patients with oral squamous cell carcinoma. METHODS: Salivary and serum IL-6 and bFGF were evaluated in a group of 33 patients (28 men, 5 women) with oral squamous cell carcinoma (OSCC), age range 40-73 years , mean 54.05 years. Control group consisted of 23 healhy participants, mean age 25 years. RESULTS: Serum IL-6 and bFGF levels were not significantly different between patients with OSCC and healthy controls. Elevated levels of salivary IL-6 and bFGF in patients with OSCC when compared to the healthy controls were found (p<0.001). CONCLUSIONS: The conclusion is drawn that higher levels of salivary IL-6 and bFGF in patients with OSCC might originate from the local production, probably from carcinoma cells.

Allogeneic peripheral blood stem cell transplantations in children--a single center experience.

We analyzed 30 peripheral blood stem cell transplantations (PBSCT) from 25 human leukocyte antigen (HLA) matched sibling donors (MSD) and 4 HLA-matched unrelated donors (MUD) in 29 patients, done between November 1996 and March 2003. Patients aged 3 to 17 years underwent allogeneic PBSCT for malignant (16 patients) and non-malignant (13 patients) diseases. Sibling donors aged 3 to 23 years were given granulocyte colony-stimulating factor (G-CSF) 5-10 microg/kg/day for 4 to 5 days. All but one of the 29 donors underwent one single leukapheresis for stem cell collection. The patients received a median of 4.2 x 10(6) CD34+ cells/kg of body weight, they all engrafted after a median of 13.5 days (range 10-25 days). Acute graft-versus-host disease (GVHD) grade II to IV developed in 11 of 26 MSD transplants and in all 4 patients after MUD PBSCT. Eleven of 27 evaluable patients experienced chronic GVHD. After a median follow-up of 662 days, 20 out of 29 patients (69%) are alive, three of them need systemic immunosuppression for chronic GVHD. Six patients experienced relapse of their underlying malignant disease, one of them still alive in complete remission. Two patients died of grade IV acute GVHD and two others due to an opportunistic infection. Based upon our experience, PBSCT is a feasible and safe method for both pediatric donors and patients. It is associated with rapid engraftment, no greater incidence of acute but a higher incidence of chronic GVHD as compared to bone marrow transplantation (BMT) and therefore suitable mainly for children suffering from malignant diseases.

Midterm follow-up study of laparoscopic dissection of uterine vessels for surgical treatment of symptomatic fibroids.

BACKGROUND: This study aimed to assess laparoscopic dissection of uterine vessels (LDUV) for symptomatic fibroids in women. METHODS: A total of 69 women entered the study between March 2000 and June 2003. In this case series, 68 consecutive women underwent LDUV using ultrasonically activated sheers or electrosurgery for the treatment of fibroids over 3 years (median follow-up period, 14.5 months). Ultrasound or magnetic resonance imaging was carried out 3, 6, 12, 24, and 36 months after treatment. The tissue markers, gonadotropin, and estrogen levels were studied postoperatively. RESULTS: Almost all the patients (98.5%) had a successful LDUV with a low rate (7.3%) of postoperative complications. The time of surgery ranged from 15 to 50 min (mean, 30.8 min). The blood loss was minimal (mean, 14.7 ml), and the hospital stay was 2.4 days. Symptom improvement (menorrhagia or dysmenorrhoea) was 93.2%, and the average reduction in the dominant myoma was 57.8% during a follow-up period longer than 12 months. All the patients with anemia had normal red cell counts after 3 months. CONCLUSIONS: Uterine volume and the dominant fibroid were significantly reduced and symptoms were improved by LDUV. The laparoscopic procedure is associated with insignificant tissue damage and normal gonadotropin and estrogen levels.

Laparoscopically assisted modified radical vaginal hysterectomy (type II) with pelvic lymphadenectomy: ultrasonic operative technique.

OBJECTIVE: The aim of this study was to incorporate an ultrasonic operative laparoscopic technique to complete a type II laparoscopically-assisted modified radical vaginal hysterectomy (LARVH) and pelvic lymph node dissection (PLND) in early cervical cancer. METHODS AND MATERIALS: LARVH type II and PLND using a laparoscopic ultrasonic operative technique and conventional vaginal surgery were indicated in five cases of early cervical cancer (IA2). RESULTS: Complete pelvic lymphadenectomy and the laparoscopic phase of modified radical vaginal hysterectomy were successfully performed using ultrasonic instruments in all women. Uterine artery and ureteral dissection with resection of the cervicovesical fascia, cardinal and uterosacral ligaments were successful with ultrasonically activated instruments only. CONCLUSION: Our initial experience with laparoscopically assisted radical vaginal hysterectomy type II confirmed that the use of a minimally invasive ultrasonic technique is feasible. Further investigations into the indications of disease where laparoscopic surgery is appropriate in the management of early cervical carcinoma are required.

Short-term results from laparoscopic dissection of uterine vessels in women with symptomatic fibroids.

OBJECTIVE: To assess the outcome, tissue trauma, clinical improvement and the reduction in size of fibroid following laparoscopic dissection of uterine vessels (LDUV). SETTING: Department of Obstetrics and Gynaecology, Endoscopic Training Centre, Baby Friendly Hospital, Kladno, Czech Republic. DESIGN: An uncontrolled case series of 17 consecutive women who underwent LDUV using ultrasonically activated shears for the treatment of fibroids over two years. Ultrasound imaging was carried out before and three and six months following treatment. The tissue markers (C-reactive protein (CRP), Interleukin-6 (IL-6), Creatin kinase (CK) and white blood cell count) were studied preoperatively, on the first and third postoperative day. RESULTS: All patients underwent successful LDUV without intraoperative complications. Tissue markers results show that the LDUV performed using ultrasonically activated shears is associated with insignificant tissue damage. Time of surgery ranged from 30 to 50min (mean 39min). Mean blood loss was less than 30ml and mean hospital stay was 2.3 days. Three and six months after surgery, respectively, average reduction in uterine volume was 23.6 and 36.8% and average reduction in dominant fibroid was 28.6 and 56.8%. 94.1% of women had improvement in menorrhagia or dysmenorrhoea, and 91.6% had improvement in bulk-related symptoms or pelvic pain six months after treatment. CONCLUSION: Uterine volume and dominant fibroid were reduced and symptoms were improved by LDUV. The procedure of laparoscopic dissection of uterine vessels can be completed within 30-40min with only minimal blood loss and short hospital stay if performed by experienced laparoscopists.

[Minimally invasive surgical treatment of symptomatic myomas using laparoscopic dissection of uterine vessels: prospective clinical study (part I)]. / Minimálne invazivní operacní lécba symptomatických myomu pomocí LDUV (laparoskopická disekce delozních cév): klinická prospektivní studie (cást I).

OBJECTIVE: To assess the clinical outcome, indication and operative technique of laparoscopic dissection of uterine vessels (LDUV) using ultrasonic technique in the treatment of symptomatic fibroids. DESIGN: Prospective case observational clinical study (Part I). SETTING: Department of Obstetrics and Gynecology, Hospital Kladno. METHODS: We analysed clinical outcome of laparoscopic dissection of uterine vessels in 46 symptomatic women with fibroids in the period 2000-2002. The operative technique and indication to surgery were studied especially in part I. RESULTS: All patients underwent successful LDUV procedure without intraoperative complications. Time of surgery ranged from 15-50 minutes (mean 37.3 minutes) in cases of LDUV only. In cases of laparoscopic dissection of uterine vessels combined with myomectomy the mean of surgery was 63.1 minutes (range 35-120). Mean blood loss was less than 25 ml and mean hospital preoperative stay 2.1 days. Only two minor febrile preoperative complications was found (4.3%). CONCLUSION: The procedure of laparoscopic dissection of uterine vessels can be completed within 25-35 minutes with minimal blood loss, short hospital stay and acceptable number of complications.

Phagocytic functions of salivary neutrophils in oral mucous membrane diseases.

BACKGROUND AND PURPOSE: Phagocytic functions of salivary polymorphonuclear neutrophils (sPMNs) have not been comprehensively studied in patients with oral mucous membrane diseases, although available data suggest the role of immunity in their pathogenesis. SUBJECTS AND METHODS: Phagocytic functions of sPMN were determined in 15 patients with acute recurrent aphthous ulceration (RAU), 11 patients with oral lichen planus (OLP) and 20 healthy volunteers. In healthy subjects, the same parameters were also determined in peripheral blood polymorphonuclear neutrophils (bPMNs). Phagocytic activity (proportion of ingesting cells, PA), ingestion ability (number of ingested targets per 100 phagocytes, IA) and intracellular microbicidity (proportion of killed targets, IM) of PMNs separated from peripheral blood and the whole unstimulated saliva were determined by acridine orange method with living yeast cells as targets. RESULTS: Salivary PMNs in healthy individuals showed significant reduction in PA (33% vs. 76%; P < 0.009) and IA (0.47% vs. 2.93%; P < 0.009) and significant increase in IM (12.0% vs. 5.5%; P = 0.011) in comparison with bPMNs. In RAU patients, reduced PA (27% vs. 37%; P = 0.035) and IA (0.25% vs. 0.47%; P = 0.05) were detected, while in OLP patients enhanced IM was detected (12% vs. 19%; P = 0.033) in comparison with healthy controls. CONCLUSION: Salivary PMNs present functional features distinct from those in peripheral blood. Some phagocytic functions of sPMNs are reduced in RAU and enhanced in OLP, indicating their role in pathogenesis or reflecting clinical changes in these conditions.

Salivary immunoglobulin A and G subclasses in HIV positive patients.

Many of the opportunistic infections in HIV are related to the mucous membranes, but the protection of oral mucosal compartment mediated by IgA and IgG subclasses in saliva is still not well documented. Therefore, the aim of this study was to investigate the status of salivary IgA and IgG subclass in HIV positive patients. Levels of IgG1, IgG2, IgG3 and IgG4 were determined by ELISA and IgA1 and IgA2 by radial immunodiffusion in the resting whole saliva of 33 HIV patients and 21 HIV-seronegative healthy controls and were expressed in mg/L (IgA) and ug/L (IgG) of saliva. Salivary IgA2 was significantly reduced in the HIV positive patients (p<0.0009) when compared to the healthy controls, but no differences in salivary IgA1 level between HIV patients and healthy controls were found. On the other hand, salivary IgG1, IgG2, IgG3 and IgG4 subclasses were increased (p<0.0009) in HIV patients in comparison to the healthy controls. We can conclude that inspite of IgA2 deficiency which was found in studied HIV positive patients, mucosal antibody responses are quite normal and might not predispose development of oral opportunistic infections.

Salivary IgA and IgG subclasses in oral mucosal diseases.

OBJECTIVE: It was hypothesized that serum levels of immunoglobulins may play a role in the pathogenesis of oral mucosal diseases, or reflect clinical changes in these conditions, but little is known about the role of salivary immunoglobulins in the pathogenesis of these diseases. The aim of this study was to investigate possible alterations in salivary immunoglobulin A (IgA) and IgG subclasses in patients with oral mucosal inflammatory diseases. SUBJECTS AND METHODS: Levels of IgG1, IgG2, IgG3 and IgG4 were determined by enzyme-linked immunosorbent assay (ELISA), and IgA1 and IgA2 by radial immunodiffusion in the resting whole saliva of 31 patients with acute recurrent aphthous ulceration (RAU) (and followed in remission), 11 patients with chronic hyperplastic candidal infection (CHC), 12 patients with Sjogren's syndrome (SS), six patients with oral lichen planus (OLP), and 18 healthy volunteers using the normal saliva as a comparison point for all. RESULTS: IgG and IgA subclasses were increased in OLP. In CHC all IgG subclasses were increased while IgA1 was decreased, IgG1, IgG3 and IgG4 levels were increased in SS, while all IgG subclasses as well as IgA2 were increased in acute RAU in comparison with healthy controls. No differences in any immunoglobulin subclasses between major and minor acute RAU were found. In remission, IgG1 and IgG4 returned to normal values while IgG2, IgG3, and IgA2 remained increased in patients with RAU. CONCLUSION: Salivary immunoglobulin subclasses vary in different oral mucosal conditions and may play a role in oral mucosal inflammatory diseases and/or reflect clinical changes in these conditions.