Vaccination recommendations for adult patients with rheumatic diseases.

Infectious diseases in any age group can be successfully prevented through immunization. Protection provided through immunization in childhood decreases over the years. Immunization in adulthood is important because of the growing elderly population, chronic diseases, and globalization. Recommendations on this subject are being constantly updated through scientific guidelines. Immunization in adulthood is also important in rheumatology. There is an increased risk not only of infection in rheumatic diseases but also of infections being more severe. Most infections, and their frequently observed complications, are among those diseases that can be prevented through immunization. The type of immunization, immunosuppressive/immunomodulatory therapy received by the patient, disease activity, and presence of chronic diseases affect the immunization process in patients with rheumatic diseases. This review will consider the immunization process followed in rheumatic diseases and also refer to its application.

Association between single nucleotide polymorphisms in prospective genes and susceptibility to ankylosing spondylitis and inflammatory bowel disease in a single centre in Turkey.

BACKGROUND/AIMS: To establish the prevalence of the single nucleotide polymorphisms (SNPs) of endoplasmic reticulum aminopeptidase 1 (ERAP1), IL-23 receptor (IL-23R), signal transducer and activator of transcription 3 (STAT-3) and Janus kinase 2 (JAK-2) in ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) in a Turkish population. MATERIALS AND METHODS: A total of 562 subjects who presented at the Ankara University internal medicine departments of rheumatology and gastroenterology outpatient clinics were recruited in this study, including 365 patients with AS, 197 patients with IBD and 230 healthy controls. ERAP1, IL-23R, STAT-3 and JAK-2) were genotyped in competitive allele-specific polymerase chain reactions. RESULTS: The ERAP1 (rs26653) polymorphism was found to increase the disease risk in patients with AS and IBD compared with the control group (p=0.02 and p=0.01, respectively). In addition, this polymorphism revealed a significant relationship with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI) in patients with AS (r=0.829, p < 0.001 and r=0.731, p < 0.001, respectively). CONCLUSION: The ERAP1 gene polymorphism might be a risk factor in the pathogenesis of AS and IBD. In contrast, IL-23R gene polymorphisms may serve a protective role in AS and IBD.

Peripheral blood mononuclear cell microchimerism in Turkish female patients with systemic sclerosis.

OBJECTIVES: To investigate microchimerism (Mc) in peripheral blood mononuclear cells (PBMC) taken from female patients with systemic sclerosis (SSc) and healthy females. We also intended to research the association between Mc and the clinical subsets. METHODS: This study included 50 females with lcSSc, 30 females with dcSSc and 40 healthy females. The Y-chromosome sequences were studied by RT-PCR in DNA obtained from PBMC. RESULTS: Mc was found in 28 (35 %) patients and 8 (20 %) healthy controls as well as in 6 dcSSc patients with son(s) (27.3 %), 10 lcSSc patients with son(s) (32.3 %) and 7 control females with son(s) (18.9 %) (p > 0.05). Mc was detected in 6 nulliparous lcSSc patients (31.6 %) and in 1 nulliparous dcSSc patient (11.1 %) (p > 0.05). The mean time elapsed between the first pregnancy and the diagnosis of SSc was 3.5 (0-49) years in the Mc-positive patients and 14 (0-55) years in the negative patients (p = 0.020). The mean modified Rodnan skin scores (ModRSS) of the patients with and without Mc was 10 (4-24) and 13 (4-26), respectively (p = 0.038). The relationship between Mc and the system involvement, disease severity, autoantibody profile, number of children and age of children was not found. CONCLUSIONS: Various etiological factors rather than just one play a role in the development of scleroderma. Mc is thought to be one factor that shortens the elapsed time of disease development in SSc. Mc is inversely related to the ModRSS, and no association was detected between Mc and autoantibodies or the clinical subsets.

A case of Riedel's thyroiditis with pleural and pericardial effusions.

Riedel's thyroiditis (RT) is a rare type of chronic thyroiditis of unproven etiology and definite treatment. It can be associated with retroperitoneal, mediastinal, orbital, and hepatic fibrosis. Symptoms arise mainly due to compression of neighboring structures. Surgery is usually required for a definite diagnosis and decompression to relieve the symptoms. Glucocorticoids and tamoxifen are commonly used agents for the pharmacotherapy. We hereby describe the development of pleural and pericardial effusions during the clinical course of an RT case. A 39-year-old woman suffering from neck compression symptoms was admitted to the hospital. After a decompression isthmectomy, RT was diagnosed. She responded well to glucocorticoid therapy after surgery. However, symptoms reoccurred shortly after glucocorticoid withdrawal and the disease process extended to the mediastinum. Tamoxifen was started and the neck and mediastinal mass regressed and her symptoms disappeared considerably for more than 6 months. However, she was readmitted with severe dyspnea and chest pain. Further investigation revealed an exudative pleural and pericardial effusion and mediastinal enlargement. A thorough evaluation of the patient's effusions did not disclose any specific etiological insult. The patient was symptom-free with a considerable reduction of the soft tissue mass and no effusions, and treated successfully with colchicine, azathioprine, and glucocorticoids. To the best of our knowledge, this is the first case reported in the literature as an RT presenting with pleuropericardial effusions.

Circulating endothelial cells: a disease activity marker in Behçet's vasculitis?

Increased numbers of circulating endothelial cells (CECs) have previously been reported after various diseases associated with endothelial injury. The aim of this study was to evaluate the CECs in patients with Behçet's disease and to demonstrate a possible association between CECs and disease activity. Sixty individuals (45 Behçet's disease patients and 15 healthy controls) with normal renal function are included in the study. Peripheral blood samples are first incubated with antiCD146 antibody and subsequently conjugated to immunomagnetic beads to isolate CECs. Cells are stained with UEA-1 before counting. Behçet's patients [7-135 cells/mL, mean 50 cells/mL, median 43 cells/mL (SD 35), P<0.001] have elevated numbers of CECs compared to controls [3-14 cells/mL, mean 9 cells/mL, median 8 cells/mL (SD 4)]. The number of CECs is higher in the active period of the disease compared to the inactive period. Further studies are needed to demonstrate the potential prognostic importance of CECs in Behçet's vasculitis.

Serum pro-matrix metalloproteinase-3 as an indicator of disease activity and severity in rheumatoid arthritis: comparison with traditional markers.

Matrix metalloproteinase-3 (MMP-3) production increases in rheumatoid arthritis (RA) and has been proposed as a marker of disease activity and joint damage. The aim of this cross-sectional study is to examine the usefulness of serum proMMP-3 as an indicator of disease activity and severity in comparison with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Serum proMMP-3 was measured by a quantitative ELISA in 85 RA patients and 70 healthy subjects. Clinical and laboratory measures of disease activity and severity were obtained. Radiological joint damage was assessed by the method of Larsen. Serum proMMP-3 was significantly higher in RA patients than that in the healthy subjects. The active RA patients had significantly higher serum proMMP-3 than the inactive patients. Serum proMMP-3 was significantly correlated with some parameters of disease activity including swollen joints count, proximal interphalangeal joint score, morning stiffness, and Health Assessment Questionnaire; however, ESR and serum CRP were better correlated with all indicators of the disease activity than proMMP-3. The analysis of receiver operating characteristic supported that ESR and CRP had higher performance for reflection of activity compared to proMMP-3. There were no significant associations among Larsen score and proMMP-3, ESR, and CRP. Our results suggest that the cross-sectional measurement of serum proMMP-3 could not give additional information about RA disease activity compared to ESR and CRP, and could not give any information about joint damage.

The contribution of genotypes at the MICA gene triplet repeat polymorphisms and MEFV mutations to amyloidosis and course of the disease in the patients with familial Mediterranean fever.

OBJECTIVE: To evaluate the effects of MEFV genotypes and the major histocompatibility complex class I chain-related gene A (MICA) triplet repeat polymorphism on the severity and clinical features of familial Mediterranean fever (FMF) and amyloidosis in a group of Turkish FMF patients. METHODS: We evaluated 105 adult FMF patients (with or without amyloidosis, 33 and 72, respectively) along with 107 healthy controls who were neither related to the patients nor had a family history of FMF or Behcet's disease. After recording the demographic and clinical data, the predominant mutations in the MEFV gene locus (M694V, M680I, V726A, M694I, and E148Q) were investigated by direct sequencing. MICA transmembrane polymorphisms in exon 5 were studied by vertical gel electrophoresis and fragment analysis of the amplicons obtained from MICA locus with appropriate primers. RESULTS: Earlier age at onset, increased frequency of attacks, arthritis attacks, erysipelas-like erythema, increased severity scores and amyloidosis were significantly more common in M694V homozygous patients compared to the patients not M694V homozygous (P = 0.005, OR 4.55; P = 0.001, OR 7.60; P = 0.003, OR 4.57; P = 0.002, OR 7.58; P = 0.004, OR 5.15 and P = 0.018, OR 3.33, respectively). We did not detect any modifying effects of MICA alleles as an independently risk factor on the amyloidosis development. However, when we examined the effects of MICA alleles on the course of the disease and development of amyloidosis in the M694V homozygous patients, A5 allele had a protective effect against the development of amyloidosis (P = 0.038, OR(adj) 0.26 with A5 and P = 0.009, OR(adj) 4.42 without A5). CONCLUSION: Though the effects of the MEFV genotypes seem clear, there are definitely other modifying factors or genes on the development of amyloidosis and on the course of the disease. For example, some MICA alleles have a protective effect on the prognostic factors in FMF.

A case of systemic lupus erythematosus presenting with protein-losing enteropathy.

We report an unusual case of systemic lupus erythematosus presented with protein-losing enteropathy. A 24-year-old girl was referred to our hospital with generalized edema, thrombocytopenia, hypoalbuminemia, hypercholesterolemia, hypocomplementemia, antinuclear antibody (ANA) (speckled pattern) and anti- SSA/Ro positivities, and elevated CA125 antigen appeared in the blood examination. On the radiological studies, she had mild pleural effusion and moderate ascites which were transudate. A diagnosis of protein-losing enteropathy was made on the basis of increased 99mTc-labelled human immunoglobulin scintigram showing abnormal radioactivity. Endoscopic gastric, duodenal and jejunal biopsies showed chronic inflammation, but vasculitis and immune complex deposition findings were not present. Renal biopsy revealed no definitive findings of lupus nephritis. By the administration of corticosteroids, hypoalbuminemia began to improve, but steroid doses were decreased due to steroid-induced myopathy. Temporary hemiparesis and facial paralysis developed in the patients' follow up. Her cranial magnetic resonance imaging revealed chronic ischemia, and the patient was considered to have neurological involvement due to systemic lupus erythematosus. protein-losing enteropathy and other symptoms then improved dramatically after monthly intravenous cyclophosphamide (three times) combined with oral low-dose corticosteroids. The combination of azathioprine and low-dose steroids was used as maintenance medication. Although about 30 protein-losing enteropathy -associated systemic lupus erythematosus cases have been reported, the patients having initial symptoms as protein-losing enteropathy are rare in the literature. Protein-losing enteropathy -associated systemic lupus erythematosus cases probably represent a subgroup of systemic lupus erythematosus, the characteristics of which are hypocomplementemia, protein-losing enteropathy, ANA positivity showing speckled pattern and anti-ds DNA negativities. In the patients with systemic lupus erythematosus with edema and hypoalbuminemia without renal protein loss, protein-losing enteropathy-associated systemic lupus erythematosus should be kept in mind.

Macro-amylasemia in a patient with selective IgA deficiency and antiphospholipid antibodies.

We report an unusual case with macro-amylasemia with coexistent selective IgA deficiency and antiphospholipid antibodies. A 16-year-old girl was referred to us with a history of episodic abdominal pain accompanied by vomiting and diarrhea. Macroamylasemia was demonstrated by precipitation of 99% amylase activity with polyethylene glycol 6000. She had high levels of anticardiolipin IgG and beta2 glycoprotein 1 IgG antibodies in the blood, but no evidence of clinical criteria of antiphospholipid syndrome. In the literature, although macro-amylasemia has been found to occur in a variety of diseases including autoimmune disorders, to our knowledge, this is the first well-documented case of macro-amylasemia associated with selective IgA deficiency and the presence of antiphospholipid antibodies. It is important that clinicians be aware of their existence in order to avoid unnecessary procedures and that the patient is informed of the macro-amylasemia; moreover, it should be stated in the patient's health record.

A multicenter study of patients with adult-onset Still's disease compared with systemic juvenile idiopathic arthritis.

Adult-onset Still's disease (AOSD) has often been regarded as the adult spectrum of systemic juvenile idiopathic arthritis (sJIA). The present study aims to compare the clinical and laboratory features, the disease course and the response to treatment in patients having AOSD with those having sJIA. Retrospective review of all available data that were filled out by adult and paediatric rheumatologists from six centers using a standard data extraction form was performed. A total of 95 patients with AOSD and 25 patients with sJIA were recruited for the study. The frequency of fever, rash, myalgia, weight loss and sore throat was higher in patients with AOSD. The pattern of joint involvement differed slightly. Laboratory findings were similar in both groups, except that liver dysfunction and neutrophilia were more common among adults. A multiphasic pattern dominated the childhood cases, whereas the most frequent course was a chronic one in adults. Corticosteroids and methotrexate were the most commonly employed therapy; however, chloroquine was another popular therapy in the adult group. We showed a difference in the rate of clinical and laboratory features between patients with AOSD and those with sJIA. AOSD and sJIA may still be the same disease, and children may simply be reacting differently as the result of the first encounter of the putative antigens with the immune system.

A case of overlap syndrome with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis and secondary Sjögren's syndrome.

We report an unusual case of overlap syndrome that had the coexistence of five autoimmune diseases. A 45-year-old woman initially developed seropositive erosive rheumatoid arthritis (RA) 11 years ago. She then developed progressive systemic sclerosis (PSS) (including pulmonary hypertension, esophageal dysfunction, cardiac involvement and sclerodactilitis), systemic lupus erythematosus (SLE) (including photosensitivity, nephritis, leukopenia, lymphopenia, thrombocytopenia and Coombs positive hemolytic anemia and positive anti-dsDNA), and secondary Sjögren's syndrome (SSS) in the last 7 years before she was admitted to our clinic. The patient fulfilled classification criteria for RA, SLE, PSS and SSS, as determined by American College of Rheumatology. Hypothyroidism with positive autoantibodies due to Hashimoto's thyroiditis, the beginning of which could not be defined, was coexistent with this overlap syndrome. In the literature, although overlap syndromes in different combinations were reported, we very rarely observed a complex case like this patient. In our opinion, this is the first well-documented case of RA, PSS, SLE, SSS and Hashimoto's thyroiditis existing together in the same patient. Although immunosuppressive therapy was administered, the disease rapidly deteriorated and the patient died.

The prevalence of extraintestinal manifestations and HLA association in patients with inflammatory bowel disease.

To determine the prevalence, clinical and radiological characteristics of spondyloarthropathy (SpA) in patients with inflammatory bowel disease (IBD), to assess the association between HLA B27 and B51 and the extraintestinal symptoms and to evaluate whether IBD is associated with Behçet's disease (BD). One hundred and sixty-two consecutive adult patients with established diagnosis of IBD as either Crohn's disease (CD) or ulcerative colitis (UC) were evaluated. All the patients including those previously diagnosed with or without SpA had a complete rheumatologic examination and they were evaluated according to the European Spondyloarthropathy Study Group (ESSG) criteria for SpA and The International Study Group for Behçet's disease criteria for BD. The demographic and clinical data were recorded on a standardized form. The radiographies were obtained in all the patients and computed tomography (CT) was performed in the patients with suspected pelvic radiographies and/or low back pain in the physical examination. Radiological evaluation was made according to the Modified New York criteria. HLA B27, B51 and anti-neutrophile cytoplasmic antigen (ANCA) were searched in all the patients. Of the 162 patients with IBD (mean age 41.48+/-11.63 years, male 60, female 102), 78 were CD and 84 were UC. The mean of the IBD duration was 54.92+/-50.32 months and SpA duration was 20.63+/-34.37 months. The prevalence of SpA and AS in IBD was 45.7 and 9.9%, respectively. Frequencies of SpA and AS, the difference between UC and CD were not significant. Spondylitis, enthesitis, peripheral arthritis, oral ulcer and uveitis were not different between UC and CD, but erythema nodosum was found significantly more common in the CD patients compared with UC patients (P=0.005). The duration of IBD and SpA was similar in both groups. As the IBD duration increased, the prevalence of SpA development decreased (rr=0.991, P=0.009). Of the IBD patients, 13.6% were asymptomatic for musculoskeletal manifestations of SpA and their sacroiliac radiographies and CTs showed grade 2 sacroiliitis. HLA B27, B51 and ANCA positivities were not different between the patients with UC and CD. HLA B27 was significantly more common in the patients with sacroiliitis, spondylitis, enthesitis, peripheral arthritis, erythema nodosum, uveitis (P<0.001) and oral ulcer (P=0.025). BD was diagnosed in none of the patients. ANCA positivity was found to be related with the presence of erythema nodosum and uveitis (P=0.001 and P=0.005). The prevalence of SpA and AS is higher in the prospectively evaluated patients with radiological studies than those in the previously published studies. There is a high prevalence of asymptomatic sacroiliitis in IBD. An early diagnosis of inflammatory arthritis in IBD patients may prevent a disability due to SpA and AS.

Late onset rheumatoid arthritis: clinical and laboratory comparisons with younger onset patients.

We aimed to compare the clinical and laboratory profiles of the patients presenting late onset rheumatoid arthritis (LORA) with younger onset rheumatoid arthritis (YORA) patients. During the period between January 1995 and December 2004, 124 patients with LORA were identified from a retrospective chart review of inpatients and outpatients. They were compared with 150 YORA patients examined during the same period including their clinical and laboratory findings. The mean ages of the patients with LORA and YORA were 71.7+/-5.9 years, and 52.1+/-11.5 years, respectively. The gender ratio (female/male) was 1.48 in LORA and 2.85 in YORA (p = 0.012). The average ages of the disease onset were 42.2+/-10.4 years in YORA and 68.4+/-4.6 years in LORA. The duration of the diagnosis was longer in LORA than in YORA (20.7+/-14.3 months versus 10.3+/-6.2 months, p < 0.001). Rheumatoid arthritis (RA) duration was shorter in LORA than in YORA (43.5+/-64.4 months versus 126.3+/-101.0 months, p < 0.001). Although LORA patients had more significant frequent shoulder joint involvements (p < 0.001), proximal interphalangeal (PIP), metacarpophalangeal (MCP), elbow, metatarsophalangeal (MTP) and ankle involvements were common in YORA. Wrist, knee and hip involvements were not different in the groups. Classical rheumatoid hand deformities, interstitial lung disease and Sjögren's syndrome (SS) were significantly lower in LORA than in YORA. LORA patients had more common weight loss, myalgia, lymphadenopathy, polymyalgia rheumatica (PMR)-like syndrome and neuropathy. The frequencies of RF, ANA, anti-SSA/Ro and anti-SSB/La positivities were lower in LORA than in YORA, whereas elevated erythrocyte sedimentation rates (ESR), C-reactive protein (CRP) and anemia associated with chronic disease were higher in LORA. Patients with LORA, according to the accepted international criteria, present with different clinical and laboratory profiles when compared with younger patients. These results suggest that age may influence the presentation of RA at onset.

The importance of alpha-fodrin antibodies in the diagnosis of Sjögren's syndrome.

OBJECTIVE: We wanted to determine the prevalence of IgA and IgG antibodies against alpha-fodrin in the patients with primary and secondary Sjögren's syndrome (SS) and also to compare with anti-Ro and anti-La antibodies in the diagnosis of SS. METHODS: We tested the prevalence of anti-alpha-fodrin IgA, IgG, anti-Ro, anti-La antibodies, anti-nuclear antibodies (ANA) and rheumatoid factor (RF) in naive patients with primary (n = 20) and secondary SS (n = 20) (Rheumatoid Arthritis [RA]+SS, n = 10; Systemic Lupus Erythematosus [SLE] + SS, n = 10), RA (n = 10), SLE (n = 10) and in healthy controls (n = 20). Salivary gland biopsies were performed in the patients with primary and secondary SS. RESULTS: In primary SS, anti-alpha-fodrin IgA, IgG, anti-Ro and anti-La antibodies were detected as 20, 10, 55 and 20% respectively. In RA + SS, anti-alpha-fodrin IgA was detected to be 10% and IgG was negative; however, anti-Ro antibodies and anti-La antibodies were found to be 40% and 20% respectively. In SLE + SS, anti-alpha-fodrin IgA was found to be 20% and IgG was found to be 10%, but anti-Ro and anti-La antibodies were found to be 90% and 20% respectively. Alpha-fodrin antibodies were not detected in RA, SLE and healthy controls. CONCLUSION: The detection of anti-alpha-fodrin antibodies by used ELISA does not give much contribution to the diagnosis of SS, and anti-Ro and anti-La are still useful serological markers in the diagnosis of SS.

Vasculitis and expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin in salivary glands of patients with Sjögren's syndrome.

OBJECTIVE: We investigated the relationship between clinical symptoms and the grade of histopathological damage and expression of adhesion molecules in salivary glands of patients with Sjögren's syndrome (SS). METHODS: We studied untreated and recently diagnosed patients with primary (n =20) and secondary SS [10 with SS and rheumatoid arthritis (RA); 10 with SS and systemic lupus erythematosus (SLE)] and 3 healthy controls. Salivary gland biopsies were performed in patients and controls and clinical data were obtained. Salivary gland biopsies were assessed for lymphocyte focus score and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. In serum, antinuclear antibodies, rheumatoid factor, anti-Ro and anti-La antibodies, anti-alpha-fodrin IgA and IgG antibodies, and gamma-globulin concentrations were measured. RESULTS: In salivary gland samples, ICAM-1 was expressed on vascular endothelial cells and lymphocyte foci, while VCAM-1 was expressed on vascular endothelial cells and follicular dendritic reticulin cells. There was a positive correlation between lymphocyte focus score and ICAM-1 expression (p < 0.05). We detected correlation between expression of ICAM-1 and VCAM-1, and the expression of VCAM-1 was significantly related to vasculitis (p < 0.05). The areas of E-selectin expression and the dispersion and severity of staining were not correlated with the focus score or with patients' clinical features (p > 0.05). There was no correlation between the staining and autoantibody positivity and gamma-globulin levels. CONCLUSION: ICAM-1 may be important for lymphocyte recruitment and glandular damage and VCAM-1 may be important for the development of vasculitis in patients with SS.

In vitro nonspecific mitogenic response of T-cell subsets in acute and chronic brucellosis.

The aim of the present study was to determine the cellular immune response on the course of brucellosis by investigating the proliferation response of T-cell subsets to phytohemagglutinin (PHA), that is, nonspecific mitogen in the patients with acute and chronic brucellosis. The study was performed in 19 patients with untreated brucellosis (acute, n = 11; chronic, n = 8) and 19 healthy controls. Standard tube agglutination and Coombs tests for brucellosis were performed. CD4+ and CD8+ T cell were investigated by the flow cytometry and sorting methods in all of cases. After these cells were cultured and stimulated with PHA, [H3]-thymidine uptake and stimulation indices (SIs) were established. In all of the patients with brucellosis, CD4+ SIs and CD8+ SIs were found to be 1.40 +/- 0.63 and 1.45 +/- 0.42, respectively, and in the controls CD4+ SIs and CD8+ SIs were 1.59 +/- 0.36 and 1.64 +/- 0.37, respectively. In acute cases, CD4+ SIs were 1.71 +/- 0.64 and CD8+ SIs were 1.54 +/- 0.45. CD4+ SIs were 0.97 +/- 0.25 and CD8+ SIs were 1.32 +/- 0.37 in chronic cases. Although in acute cases CD4+ SIs and CD8+ SIs were not different from those in the control group, CD4+ SIs of chronic brucellosis cases were found to be significantly low as compared with those of acute brucellosis cases and the controls (P < 0.01). CD8+ SIs of acute and chronic brucellosis cases were not found to be different from those in the controls. Brucella agglutination titers of the patients with acute and chronic brucellosis were not found related with CD4 SIs and CD8 SIs. The findings of significantly low results of CD4+ T-cell proliferative responses of chronic brucellosis to PHA as compared with control and acute brucellosis cases remind that the development of chronic infection might be a result of T-helper proliferation defect.

Intraperitoneal hyperthermic perfusion may induce bacterial translocation.

BACKGROUND/AIMS: Intraperitoneal hyperthermic perfusion (IPHP) has been used widely in oncologic practice. Hyperthermia is known to decrease the interstitial pressure. Also intraperitoneal hyperthermia may alter the intestinal mucosal barrier and the intestinal bacterial flora. These changes may lead to bacterial translocation (BT). To the best of our knowledge, there is no data about the possible role of IPHP on BT. METHODOLOGY: Fifty-one rats were divided into two groups. Group I (n=36) received IPHP by heated isotonic salt solution at a temperature of of 43.0 degrees C and group II (n=15) received intraperitoneal normothermic lavage by isotonic salt solution at 37.0 degrees C. Each group was divided into three subgroups which were sacrificed at 1st (Ia, IIa), 3rd (Ib, IIb) and 7th (Ic, IIc) days. Mesenteric lymph nodes (MLN), spleen and liver were sampled and cecal aspirates were obtained. The presence of viable bacteria in samples was noted. Cecal bacterial population levels (CBPL) were reported as colony forming units (CFU). Groups were compared in terms of BT and CBPL. RESULTS: BT was not detected in the Ia (IPHP, 1st day) and IIa,b,c (all control groups). However, statistically significant BT was observed in group Ib and Ic (83.3% and 66.6%, respectively) in comparison to control group (p<0.01). Also there was positive correlation between CBPL and BT. CONCLUSIONS: Intraperitoneal hyperthermia causes remarkable BT. This may explain septic complications after IPHP. Further studies are necessary to better understand the effects of IPHP on the pathophysiology of BT.

Oxidative stress and antioxidant status in elderly diabetes mellitus and glucose intolerance patients.

Increased oxidative stress and impaired anti-oxidant defense have been suggested as contributory factors for initiation and progression of complications in diabetes mellitus. Aging itself has been shown to be along with increased oxidative stress and lower anti-oxidant defense. We aimed at investigating oxidative stress and anti-oxidant enzymes in 61 elderly subjects. Fifteen healthy individuals (group 1, mean age 72.2 +/- 5.13), 13 glucose intolerant patients (group 2, mean age 71.7 +/- 4.9), 19 patients with type 2 diabetes mellitus (T2DM) without any complication (group 3, mean age 70.0 +/- 6.0), and 14 patients with T2DM with at least one complication (group 4, mean age 69.8 +/- 4.7) were included in the study. Whilst plasma levels for malondialdehyde (MDAP) and erythrocyte malondialdehyde (MDAE) were measured as markers of oxidative stress, activity of erythrocyte superoxide dismutase (SOD), glutathion peroxidase (GSH-Px), and catalase (CAT) were taken as markers of oxidative defense system. MDAP level was significantly elevated in group 4 (P = 0.001). MDAE was elevated in patients with T2DM, particularly in group 4, however, the difference between the groups was of borderline significance (P = 0.07). Whilst CAT was elevated in groups 3 and 4 compared to control subjects (P = 0.025 and 0.002, respectively), no difference was found for SOD between the groups. GSH-Px activity was found to be increased in groups 2, 3 and 4, it did not reach statistical significance (P = 0.106). There were significant correlations between CAT and MDAE (P < 0.0001, r = 0.056) and MDAP (P = 0.016, r = 0.306). These results suggest that there was an increased oxidative stress in elderly diabetics, however, this is not due to reduced erythrocyte antioxidant defense potential but, rather, increased free radical production possibly due to hyperglycemia.

Octreotide inhibits hepatic fibrosis, bile duct proliferation and bacterial translocation in obstructive jaundice.

BACKGROUND/AIMS: The protective effect of octreotide on bacterial translocation, bile duct epithelial proliferation and hepatic fibrosis was studied in an experimental obstructive jaundice model. METHODOLOGY: Forty-five healthy Wistar albino rats were randomly divided into three groups. Group I (n = 15): Median laparotomy and common bile duct manipulation performed (Sham group). Group II (n = 15): Laparotomy and common bile duct ligation performed. Group III (n = 15): After laparotomy and common bile duct ligation octreotide (Sandostatin, sandoz) was given. Simultaneously group I and II received 3 cc 0.9% NaCl and group III received 20 micrograms/kg/daily octreotide subcutaneously every 8 hours during 9 days. Two days after the procedure all rats were opened under ether anesthesia and sterile conditions. Group I had simple laparotomy but group II and III also had common bile duct ligation by 5/0 prolene. Seven days after the surgery (9th day after treatment) all rats underwent laparotomy and tests for bacterial translocation, liver biochemical tests and histopathologic analysis of liver and small bowel were carried out. RESULTS: In group II cecal population levels of bacteria were significantly higher than group I and group III (p < 0.05). In group II there was also statistically significant bacterial translocation to the mesenteric lymph nodes. Pathological changes were found in terminal ileum samples in group II which seemed to improve in group III. Hepatocyte function was preserved with octreotide treatment which also significantly decreased bile duct proliferation and periportal fibrosis in response to biliary obstruction. CONCLUSIONS: This experimental study showed that octreotide is effective in preventing bacterial translocation, bile duct proliferation and hepatic fibrosis in obstructive jaundice.

An assessment of the effect of Ginkgo Biloba EGb 761 on ischemia reperfusion injury of intestine.

BACKGROUND/AIMS: The aim of this study was to determine the effect of Ginkgo Biloba (EGb 761) on reperfusion injury of the small bowel. METHODOLOGY: Forty-eight male 200-250 g Spraque-Dawley rats in six groups were used to determine the biochemical and histopathological changes after a 30-min ischemia and 30-min reperfusion. Pre-treatment with 50 mg/kg EGb 761 (Tebofortan, Karlsruhe-Germany) or 10-mL/kg saline was administered intravenously in the treatment and control groups. The superior mesenteric artery was occluded distal to the right colic artery and collateral arcades were ligated to provide complete ischemia. Ischemia was determined by the existence of pulseless or pale color of the small intestine. The return of the pulses and the reestablishment of the pink color were assumed to be the reperfusion of the intestine. Rats that were administered Egb 761 and saline were subjected to laparotomy, ischemia, or ischemia-reperfusion procedures. Mucosal lesions were graded from 0 to 5 in histopathological examination. Malondialdehyde and myeloperoxidase levels of the intestinal mucosa were measured. RESULTS: No significant difference was noted between the control and treatment groups regarding the histopathological changes. Although malonyldialdehyde and myeloperoxidase levels of the reperfusion + EGb 761 group were slightly higher than the laparotomy + saline group, they were significantly lower than the reperfusion + saline group. CONCLUSIONS: We concluded that EGb 761 pre-treatment before ischemia-reperfusion decreased malondialdehyde and myeloperoxidase levels and attenuated the mucosal damage.