Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases

Commensal microflora (normal microflora, indigenous microbiota) consists of those micro-organisms, which are present on body surfaces covered by epithelial cells and are exposed to the external environment (gastrointestinal and respiratory tract, vagina, skin, etc.). The number of bacteria colonising mucosal and skin surfaces exceeds the number of cells forming human body. Commensal bacteria co-evolved with their hosts, however, under specific conditions they are able to overcome protective host responses and exert pathologic effects. Resident bacteria form complex ecosystems, whose diversity is enormous. The most abundant microflora is present in the distal parts of the gut; the majority of the intestinal bacteria are Gram-negative anaerobes. More than 50% of intestinal bacteria cannot be cultured by conventional microbiological techniques. Molecular biological methods help in analysing the structural and functional complexity of the microflora and in identifying its components. Resident microflora contains a number of components able to activate innate and adaptive immunity. Unlimited immune activation in response to signals from commensal bacteria could pose the risk of inflammation; immune responses to mucosal microbiota therefore require a precise regulatory control. The mucosal immune system has developed specialised regulatory, anti-inflammatory mechanisms for eliminating or tolerating non-dangerous, food and airborne antigens and commensal micro-organisms (oral, mucosal tolerance). However, at the same time the mucosal immune system must provide local defense mechanisms against environmental threats (e.g. invading pathogens). This important requirement is fulfilled by several mechanisms of mucosal immunity: strongly developed innate defense mechanisms ensuring appropriate function of the mucosal barrier, existence of unique types of lymphocytes and their products, transport of polymeric immunoglobulins through epithelial cells into secretions (sIgA) and migration and homing of cells originating from the mucosal organised tissues in mucosae and exocrine glands. The important role of commensal bacteria in development of optimally functioning mucosal immune system was demonstrated in germ-free animals (using gnotobiological techniques). Involvement of commensal microflora and its components with strong immunoactivating properties (e.g. LPS, peptidoglycans, superantigens, bacterial DNA, Hsp) in etiopathogenetic mechanism of various complex, multifactorial and multigenic diseases, including inflammatory bowel diseases, periodontal disease, rheumatoid arthritis, atherosclerosis, allergy, multiorgan failure, colon cancer has been recently suggested. Animal models of human diseases reared in defined gnotobiotic conditions are helping to elucidate the aetiology of these frequent disorders. An improved understanding of commensal bacteria-host interactions employing germ-free animal models with selective colonisation strategies combined with modern molecular techniques could bring new insights into the mechanisms of mucosal immunity and also into pathogenetic mechanisms of several infectious, inflammatory, autoimmune and neoplastic diseases. Regulation of microflora composition (e.g. by probiotics and prebiotics) offers the possibility to influence the development of mucosal and systemic immunity but it can play a role also in prevention and treatment of some diseases.     

Regenerative nodule mimicking hepatocellular carcinoma in a cirrhotic child due to hepatitis B: an imaging dilemma

Viral hepatitis B, post-hepatitic cirrhosis and hepatocellular carcinoma (HCC) is the classical sequence of events in hepatitis B virus (HBV) infected children and serum Alpha-fetoprotein (AFP) and ultrasound (USG) screening is recommended during follow up. We present a 13-yr-old girl with cirrhosis related to chronic HBV infection with normal AFP level and a 4 cm mass appearance by USG. Contrast spiral evaluation computed tomography (CT) study demonstrated a single mass located at 8th segment of the liver. Pre-contrast CT and portal venous phase studies showed heterogeneous liver parenchyma without mass appearance. HCC was suspected based on strong arterial enhancement. Two mediastinal lymphadenopathies, 1 cm under the xyphoid and 2 cm above the pericardium, were detected by thorax CT. Mediastinal exploration was undertaken with living related liver transplant donor in a second operating room. She was transplanted with the right lobe of her ABO compatible mother after evaluation of the lymph nodes revealed reactive histology by frozen section. Histologic evaluation of the explant liver documented cirrhosis with a cirrhotic nodule without histologic malignant evidence. False negative results from screening methods are familiar in the literature; however false positivity of a contrast CT study is rare. The significance of screening methods is discussed.     

Impact of liver transplantation on renal function of patients with congenital hepatic fibrosis associated with autosomal recessive polycystic kidney disease

Congenital hepatic fibrosis (CHF) is an uncommon autosomal recessive malformation. It may be associated with extrahepatic manifestations such as polycystic kidney disease. The main consequence is portal hypertension and bleeding from varices. Despite liver transplantation as a therapeutic option for this patient, long-term impact of liver transplantation on renal functions of patients with autosomal recessive polycystic kidney disease with associated liver disease is not well known. In this study, we aimed to analyze the patient's renal function after liver transplantation by creatinine clearance, glomerular filtration rate, and renal resistive indexes. Between March 1997 and September 2002, three of 50 orthotopic liver transplantation (OLT) were performed because of CHF associated with ARPKD at Ege University Organ Transplantation and Research Center. Baseline immunosuppression consisted of prednisone and cyclosporine A (CSA). The mean follow-up of the patients was 2.1 yr. Blood urea and creatinine levels were decreased after operation in all patients and remained within the normal range at the sixth and 12th month, whereas the level of the third patient were increased at the 18th month. RRI values of patients were not found different at the sixth month whereas, RRI values of patients were decreased at the 12th month and remained unchanged at the 18th month of follow-up. During the study period hypertension developed in one patient at the 16th month and resolved with antihypertensive treatment and decreasing dosage of CSA. Kidney function has remained satisfactory in all of the patients despite the use of cyclosporine. OLT can provide good survival in patients with CHF associated with ARPKD.     

The use of pulmonary autograft patch for type A aortic interruption and Swiss-cheese ventricular septal defect (VSD)

The surgical management of the aortic arch pathologies is controversial. Primary anastomosis and patch aortoplasties combined with end-to-end anastomosis have some complications like recurrence and aneurysm formation. Surgical repair of apical muscular (Swiss-cheese) defects is also still under debate. A 6-year-old patient with diagnosis of type A aortic arch interruption and Swiss-cheese ventricular septal defect (VSD) underwent successful intracardiac repair and aortic arch reconstruction. Aortic arch reconstruction was done by end-to-side anastomosis of distal aortic archus and thoracic aorta without cardiopulmonary bypass. The anterior side of the anastomosis was augmented by using pulmonary autograft patch and this patch was extended to the inferior surface of the archus aorta. Swiss-cheese VSD was repaired with a single patch using septal obliteration technique via transatrial approach. Pulmonary autograft patch aortoplasty and end-to-side anastomosis may be an alternative surgical management for surgical repair and it may be done without the need for cardiopulmonary bypass. In these patients associated multiple apical muscular VSDs can be repaired with a single patch, septal obliteration technique.     

Physician recommendations regarding tamoxifen and patient utilization of tamoxifen after surgery for ductal carcinoma in situ

BACKGROUND: To date, the impact of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 trial reported in 1999 on the use of tamoxifen after surgery for ductal carcinoma in situ (DCIS) is unknown. The current study was designed to evaluate the impact of NSABP B-24 on current practices at a comprehensive cancer center. METHODS: The records of 350 consecutive patients with DCIS who were treated at the authors' institution between July 1999 and June 2002 were obtained from a prospective database and analyzed. Whether patients were offered tamoxifen, whether patients accepted tamoxifen, and the associated reasons were recorded along with tamoxifen-related side effects and patient compliance with therapy. Clinical and pathologic factors were evaluated for their impact on recommendations regarding tamoxifen. Differences were assessed by chi-square analysis. RESULTS: Of the 350 patients, 73 were excluded because of evidence of invasive carcinoma on final pathology review. Of the remaining 277 patients, 166 patients (60%) were offered tamoxifen, and 90 patients (54%) chose to take tamoxifen. Of 111 patients who were not offered tamoxifen, 39 patients (35%) had documented explanations, which included bilateral mastectomy (n = 25 patients), medical reasons (n = 10 patients), and already received tamoxifen for other reasons at the time of diagnosis (n = 4 patients). Of 94 patients who received tamoxifen, 20 patients (21%) discontinued use because of side effects or complications. Tamoxifen was more likely to be recommended for women who underwent segmental resection compared with women who underwent total mastectomy (P = 0.002) and for women with smaller pathologic DCIS tumors (P = 0.001). In addition, these two factors were interrelated. CONCLUSIONS: Physicians and patients remain cautious regarding the use of tamoxifen after local treatment for DCIS. The current findings have implications for current trials evaluating aromatase inhibitors and other chemopreventive agents for this disease.     

The evaluation of Outpatient Smoking Cessation Clinic results

Cigarette smoking is an intractable public health problem and health care providers play a important role in the effort to reduce the prevalence of smoking. Our outpatient smoking cessation clinic started working in April 2000. Since then it has been servicing once a week by appointment. After smoking habits and sociodemographic features of the people were asked all individuals attended a suitable smoking cessation program. The results were analyzed with Chi-square test and Kaplan Meier survival analysis. It was observed that 226 people, 97 (42.9%) women and 129 (57.1%) men, visited the polyclinic during this period. The average age was 37.8 +/- 11.8 years. The rate of the smoking cessation was 43.4% at the end of the year. There were no relations between smoking cessation and initial age (p= 0.677), duration of smoking (p= 0.367), number of daily cigarette (p= 0.712), and nicotine addiction level (p= 0.673) and education level (p= 0.131). We think that our results are important to show the importance of professional support in stopping smoking.     

Current therapeutic approaches in childhood chronic hepatitis B infection: a multicenter study

BACKGROUND AND AIM: The aim of the present study was to compare the therapeutic efficacy of three different regimens in childhood chronic hepatitis B (CHB) infection. METHODS: A total of 182 children with CHB infection were prospectively allocated to three random groups. Sixty-two patients in the first group received high-dose interferon (IFN)-alpha 2b (10 MU/m2) thrice/weekly alone for 6 months. In the second (n = 60) and third groups (n = 60), IFN-alpha was used for 6 months (5 MU/m2) thrice/weekly in combination with lamivudine (LAM) (4 mg/kg, maximum 100 mg/day) for 12 months. Lamivudine was started simultaneously with IFN in the second group, while it was started 2 months prior to IFN injections in the third group. RESULTS: The initial mean alanine aminotransferase (ALT) values for the first, second and third groups were 109 +/- 93 IU/L, 101 +/- 64 IU/L and 92 +/- 42 IU/L, respectively (P > 0.05). At the end of the therapy, ALT values decreased to 82 +/- 111 IU/L, 38 +/- 41 IU/L and 29 +/- 16 IU/L in groups 1, 2 and 3, respectively. The mean ALT value of the first group was significantly different to the second and third groups (P = 0.046 and P = 0.002, respectively) at the end of the therapy and these differences were found to be sustained after 18 months. However, results in the second and third groups were similar (P > 0.05). There were no significant differences in HBeAg clearance and anti-HBe seroconversion at the initial stage, 12 months and 18 months between the three groups (P > 0.05). Hepatitis B virus (HBV) DNA clearance in the first group was different from the second and third groups, while the second and third groups had similar HBV DNA clearance ratios at 12 and 18 months. No significant difference was found in the complete response (normalization of ALT, clearance of HBV DNA and seroconversion of anti HBe) ratios of all groups (at 12 months: 28.8, 45.5, 35.8% and at 18 months 33.3, 49 and 34% in groups 1, 2 and 3, respectively, P > 0.05). CONCLUSIONS: Although the ALT normalization and HBV DNA clearance ratios of IFN plus LAM combination groups were better than the high-dose IFN-alpha monotherapy group, no significant difference was found in the complete response ratios of all three groups.     

Topical imiquimod 5% cream in external anogenital warts: a randomized, double-blind, placebo-controlled study

The complete treatment of anogenital warts has not been obtained with any combination of methods; therefore, new methods are still under investigation. In this study the activity and side effects of imiquimod 5% cream were investigated. The study group consisted of 23 male and 11 female volunteers and the control group of 9 male and 2 female volunteers. Patients applied the cream three times a week, every other day in the evenings for a period of 12 weeks. After the treatment, patients were regularly monitored for six months for recurrences. At the end of the study, 23 (69.7%) patients (all of females and 54.5% of males) in the study group displayed a complete clearance, 9 patients displayed 50-90% clearance and 1 patient displayed less than 50% clearance. In the control group, only 1 patient displayed a complete clearance, 1 patient displayed 50-90% clearance, and the other 8 patients showed no alteration in the lesions. These results were statistically significantly different (p<0.01). In 15 patients in the study group, no side effects were reported; the most frequently seen side effects were erythema and erosion. In six patients that were observed for a period of six months, recurrences occurred. Imiquimod 5% cream is a topically applied medicament that should be considered as an effective and reliable medical option in the treatment of anogenital warts.     

In vitro effect of levofloxacin and vancomycin combination against high level aminoglycoside-resistant enterococci

The in vitro effects of levofloxacin and vancomycin in combination were evaluated against high level aminoglycoside-resistant (HLAR) enterococci using chequerboard and time-kill curve techniques. We examined 28 strains of enterococci comprising 17 Enterococcus faecalis, 10 E. faecium and one E. durans. The combination of vancomycin and levofloxacin had indifferent activity against all isolates according to chequerboard microdilution method, but was synergistic for two isolates, one E. faecium and one E. faecalis, using the time-kill curve method. Both strains were levofloxacin resistant and had high level aminoglycoside resistance to gentamicin and streptomycin. Antagonism was not detected in any strain. The results of this study suggested that the combination of vancomycin with levofloxacin does not often show synergistic effect against high level aminoglycoside-resistant enterococci.