Role of intestinal transit in the pathogenesis of gallbladder stones

The aim of the study was to compare the occurrence and levels of A. actinomycetemcomitans, P. gingivalis, and P. intermedia in the subgingival plaque from sites with and without early periodontitis in adolescents using an ELISA. 47, 15- to 16-year-old adolescents (39 Indo-Pakistani, 8 white Caucasian) were examined for clinical attachment level, probing depth, supragingival plaque, subgingival calculus and bleeding on probing on the mesio-buccal and disto-buccal aspects of the 1st molars and the incisors. Based on the clinical data, 2 sites per subject were selected for subgingival plaque sampling 3 weeks later: in 32 subjects with loss of attachment > or = 1 mm, a diseased site (D) and a healthy comparison control site (C) were sampled; in 15 subjects in whom loss of attachment had not yet developed, 1 of the upper molar sites was selected, called the at-risk site (R), together with a C site. The presence and levels of A. actinomycetemcomitans, P. gingivalis, and P. intermedia were determined using an ELISA. The loss of attachment subgroup had significantly more pockets > or = 4 mm, subgingival calculus and bleeding on probing (p < 0.05). Significantly more of the D than C sites had P. gingivalis both at detectable and at measurable levels (p < 0.05). In subjects who had no loss in clinical attachment levels, fewer sampled sites harboured any of the suspected periodontopathogens investigated, and no significant differences were found between the R or C sites (p > 0.05). Although there was a significantly higher prevalence and extent of loss of attachment > or = 1 mm in the Indo-Pakistani subjects compared with the Caucasians (p < 0.05), no differences could be identified in the distribution of the bacteria. It is concluded that monitoring of the subgingival plaque may be useful in studies of early periodontitis in adolescents, and the role of P. gingivalis needs to be elucidated in prospective longitudinal investigations.     

Overlapping peptide-binding specificities of HLA-B27 and B39: evidence for a role of peptide supermotif in the pathogenesis of spondylarthropathies

OBJECTIVE: Previous studies indicated the increase of HLA-B39 among HLA-B27 negative patients with spondylarthropathies (SpA). This study was performed to examine whether the natural ligands of HLA-B27 are capable of binding to HLA-B39. METHODS: Peptides were synthesized according to the sequences of known natural ligands of HLA-B27 or B39 and were tested for their binding to HLA-B*3901 and B*2705 by quantitative peptide binding assay, using a TAP-deficient RMA-S cell line transfected with human beta2-microglobulin and HLA class I heavy chain genes. RESULTS: Four of the 10 HLA-B27 binding peptides significantly bound to HLA-B*3901. All 4 peptides had hydrophobic/aromatic amino acids (Leu or Phe) at the C-terminus. In contrast, peptides with basic residues (Lys, Arg) or Tyr at the C-terminus did not bind to B*3901. In parallel experiments, 1 of the 2 natural ligands of HLA-B*3901 was found to bind to B*2705. CONCLUSION: A subset of natural HLA-B27 ligands was capable of binding to B*3901. In addition to Arg at position 2 (Arg2), hydrophobic/aromatic C-terminal residues, such as Leu or Phe, seemed to be crucial for the cross-specificity. These results suggested that HLA-B27 and B39 recognize overlapping peptide repertoires, supporting the hypothesis that the peptides presented by both of these class I antigens play a role in the pathogenesis of SpA.     

Significance of systemic inflammation in 1,278 trauma patients

The association between the increasing severity of systemic inflammatory response syndrome (SIRS) and the incidence of post-traumatic complications and mortality was retrospectively investigated in 1278 injured patients. Patients were divided into three groups according to their Injury Severity Score (ISS) (group A: ISS > or = 9 < or = 16 points (n = 626); group B: ISS > 16 < 40 points (n = 589); group C: ISS > or = 40 points (n = 63). SIRS was defined according to the criteria of the American Consensus Conference. The number of fulfilled criteria determined its severity: moderate SIRS: 2 criteria fulfilled, intermediate SIRS: 3 criteria fulfilled, severe SIRS: 4 criteria fulfilled. Additionally, acute respiratory distress syndrome (ARDS) was defined according to the Murray-Score and the multiple organ dysfunction syndrome (MODS) according to the Goris-Score. The incidence of SIRS was 42% in group A, 70% in group B and 100% in group C (p < 0.05). The severity of SIRS increased with severity of trauma. Moreover, 178 of all injured patients (14%) developed septic complications. In parallel to SIRS, the incidence of these septic complications correlated with the severity of trauma. The occurrence and severity of ARDS and MODS correlated with increased severity of SIRS and septic complications. Among patients without SIRS 15% developed ARDS and 21% MODS. In contrast, patients with severe SIRS and septic complications demonstrated ARDS in 99% and MODS in 97%. In these patients, no correlation was found between the ISS and the incidence of ARDS or MODS. There were also stepwise increases in mortality rates in the hierarchy from SIRS to septic shock. While 13 of patients with modest SIRS (5%) and 32 of patients with intermediate SIRS (13%) died, the mortality rate of patients with severe SIRS was 19% (P < 0.05). In addition, a significant correlation between the incidence of septic complications and mortality was found. Injured patients with sepsis died in 13%, those with severe sepsis in 23%, and patients with septic shock in 33% (p < 0.05). Thus, the increasing severity of SIRS was associated with the occurrence of posttraumatic ARDS, MODS, and mortality. Using the number of fulfilled SIRS criteria for classifying systemic inflammation, its severity may be predictive for posttraumatic complications and outcome of injured patients.     

Local and systemic effects of macrophage cytokines in intestinal inflammation

The activation of macrophages and newly recruited monocytes appears to be common to both Crohn's disease and ulcerative colitis, despite different inductive stimuli. Similar activation occurs acutely during the course of invasive intestinal infections such as shigellosis, but is then usually downregulated. The macrophage cytokines tumor necrosis factor-alpha and interleukin-1 (IL-1) are centrally involved in the local inflammatory response, and blockade of either cytokine greatly attenuates the inflammatory lesion. Induction of focal vascular thrombosis and matrix degradation are thought to be an important component of this focal damage. Both cytokines and IL-6 are now recognized to contribute to the systemic effects of intestinal disease, including growth suppression, anorexia, and chronic anemia. Disturbance of sleep patterns, mood, and affect may also occur, and recent evidence points towards bidirectional interplay between macrophage cytokines and central nervous system function.     

Computed tomography of sternoclavicular joint lesions in spondylarthropathies

To evaluate the computed tomography (CT) findings of inflammatory lesions of the sternoclavicular joints (SCJ) in spondylarthropathies. DESIGN AND PATIENTS: CT scans of the SCJs were obtained in 23 patients (group 1) with inflammatory SCJ lesions in spondylarthropathies. These scans were reviewed by four readers and compared with the CT scans of 23 matched controls (group 2). Each reader had to complete a 27-item grid. RESULTS AND CONCLUSION: In the 23 patients of group 1, the mean number of observed signs was 5.3 +/- 4.2 higher (P < 0.01) than in the group of 23 matched controls (2.4 +/- 1.6). Four signs were more frequently observed (P < 0.05) in group 1: surrounded subchondral clavicular erosions and cysts, surrounded subchondral sternal cysts and sternal bone sclerosis. A cyst and/or an erosion was associated with hyperostosis and/or bone sclerosis in 9 of 23 patients in group 1. This association was not observed in group 2; the difference was significant (P < 0.001). A cyst and/or an erosive lesion was observed 18 times in group 1 versus 11 times in group 2; the difference was significant (P < 0.05). Conversely, signs of degenerative lesions (osteophytes, subchondral sclerosis, unevenness of joint surface) were no more frequently observed in controls than in group 1. This study emphasizes the diagnostic value of CT, in particular in the identification of inflammatory lesions, even when pre-existing degenerative disease is present.     

Fimbrial expression in enteric bacteria: a critical step in intestinal pathogenesis

The ability of species of enteric bacteria to recognize and colonize unique niches along the intestine is mainly based on receptor distribution and interpretation of a combination of environmental signals leading to the expression of specific adherence factors. Such elaborate orchestration of events is critical during the initial steps of pathogenesis.     

Peripheral effects of opioids in a model of chronic intestinal inflammation in mice

The study describes a model of chronic intestinal inflammation in mice. Inflammation was induced by the administration of one dose of croton oil (CO) (acute CO) or two doses (chronic CO) of intragastric CO, whereas controls received saline (SS); GI transit was measured with charcoal. Chronic CO induced intestinal inflammation substantiated by optical microscopy, weight loss (20%) and a 25% increase in GI transit. The ED50 values in SS animals were 1.67 +/- 0.13 mg/kg for morphine and 0.038 +/- 0.006 mg/kg for fentanyl; chronic CO significantly decreased the ED50 values to 0.16 +/- 0.03 mg/kg (morphine) and 0.006 +/- 0.0005 mg/kg (fentanyl). Thus the potency of morphine increased 10.4 times and that of fentanyl 6.3 times. The effects of enkephalin, but not those of U-50488H, were also significantly enhanced during chronic CO. The antitransit effects of p.o. loperamide increased 11.7 times during chronic CO. All effects were reversed by specific antagonists. The fraction of the active opioid receptor that mediates the antitransit effects of morphine was evaluated using beta-funaltrexamine. In chronic CO, the doses of beta-funaltrexamine needed to antagonize 1 mg/kg of morphine were significantly higher than in SS and acute CO, and the ED50/KA ratio was 20 times lower. These results suggest an increase in the active concentration of mu-opioid receptors during chronic inflammation.     

Significance of elevated hemoglobulin A1c for the pathogenesis of diabetic retinopathy

The hemoglobin of 70 diabetics with retinopathy was analysed. 56 patients had pathologically elevated values, 12 values were within the upper normal limit and in 2 cases the findings were normal. This hemoglobin variant is characterized by an increased affinity of oxygen. Clinically and pathologically speaking the elevated HbA1c value could be a causal factor in diabetic retinopathy. Comparisons with sickle cell anemia and thalassemia seem to indicate that hemoglobinopathy and retinopathy are pathogenetically related.     

Role of nitric oxide and platelet-activating factor in the initiation of indomethacin-provoked intestinal inflammation in rats

Some C-type lectins possess phospholipid-binding ability, which may be of physiological importance. Human mannan-binding lectin (MBL) was found to bind specifically to solid-phase phosphatidylserine (PS), phosphatidylinositol (PI) and phosphatidylcholine (PC), but not cardiolipin (CL), in a concentration-dependent manner. This property was inhibited by EDTA and by monosaccharides, and exhibited a similar pH dependence to the carbohydrate (mannan)-binding activity of MBL. These findings may be of immunological relevance.     

Significance of prion protein in transmission of prions and in pathogenesis of spongiform encephalopathies

Prion disease or transmissible spongiform encephalopathies are caused by novel pathogens termed prions. Unlike classical infectious agents such as viruses or bacteria, prions lack an independent genome and consist largely if not entirely of an abnormal form of the host-encoded prion protein. How prions multiply is not known. A wealth of experimental evidence supports an essential role for the host-encoded prion protein in susceptibility and pathogenesis of prion diseases and in the propagation and spread of prions. In addition, B lymphocytes have been found to play a crucial role in the neuroinvasiveness of prions.     

Regulation of proliferation of human colonic subepithelial myofibroblasts by mediators important in intestinal inflammation

An increase in myofibroblast number may be necessary for wound healing but may also lead to postinflammatory scarring. We have, therefore, studied the role of mediators important in inflammatory bowel disease in regulating proliferation of human colonic myofibroblasts. Using primary cultures of these cells, we have shown increases in [3H]thymidine incorporation in response to platelet-derived growth factor (EC50 = 14 ng/ml), basic fibroblast growth factor (EC50 = 2.2 ng/ml), and epidermal growth factor (EC50 = 1.1 ng/ml). Coulter counting of cell suspensions demonstrated increases in cell number with these growth factors along with insulin-like growth factor-I and -II. In addition the proinflammatory cytokines IL-1beta and TNF-alpha produced increases in [3H]thymidine incorporation. IL-1beta and platelet-derived growth factor together produced an increase in [3H]thymidine greater than either agonist alone; this effect was not, however, seen when we examined changes in cell numbers. Finally, we demonstrate a mechanism whereby these responses may be downregulated: vasoactive intestinal peptide (1 microM) elevates cyclic AwMP in these cells 4. 2-fold over control and produces a dose-related inhibition of platelet-derived growth factor-driven proliferation with a maximum inhibition of 33% at 1 microM.     

Acute and chronic effects of different bile acids on indomethacin-induced intestinal inflammation

The role of bile acids in the pathogenesis of bowel inflammation is unknown. The objective of this study was to determine whether urso- (UDC), cheno- (CDC), and taurochenodeoxycholic acid (TCDC) exert a pro- or antiinflammatory action in the acute and chronic phase of the indomethacin model of a long lasting ileitis in rats. Short-term and long-term inflammatory responses (48 h and 10 days, respectively) after two subcutaneous indomethacin (Indo) injections were elicited in rat small bowel and mesentery. To distinguish between common and model-specific effects bile acids were tested also in another model of acute inflammation induced by mesenteric superfusion with leukotriene B4(LTB4). The number of adherent and emigrated leukocytes, leukocyte rolling velocity, and venular wall shear rate were monitored in normal and inflamed postcapillary venules, and fecal pH of ileal contents which has been shown to correlate with degree of inflammation was measured, 6.5- and 2.3-fold increases in leukocyte adherence and comparable increments in leukocyte emigration were observed 48 h and ten days after indomethacin treatment, respectively. UDC, CDC, and TCDC (10 mg/kg) given daily from Indo administration until the experiment attenuated the leukocyte adherence and emigration responses elicited by indomethacin in short- and long-term inflammation. This effect was accompanied by a significant increase of fecal pH which had been lowered by indomethacin. None of the bile acids reduced the LTB4-induced increases in adherence and emigration. Oral administration of UDC, CDC, and TCDC reduces leukocyte adhesion and emigration in acute and chronic stages of Indo-induced inflammation. This could be due to the alkalizing effect of these bile acids on fecal pH which has been shown to correlate with a decrease of leukocyte-endothelial cell interactions but--according to the missing effectiveness in another model of intestinal inflammation--not to specific influences on leukocyte-endothelial cell adhesion.     

Validation of the European Spondylarthropathy Study Group and B. Amor criteria for spondylarthropathies in Lebanon

OBJECTIVES: 1) To validate European Spondylarthropathy Study Group (ESSG) and B. Amor's criteria for spondylarthropathies in Lebanon. 2) To evaluate the frequency of spondylarthropathies in rheumatological practice in Lebanon. PATIENTS AND METHODS: Cases of definite and probable spondylarthropathy were diagnosed based on the clinical judgement of participating rheumatologists, without reference to the two criteria sets under study. The first two patients without spondylarthropathy seen after each spondylarthropathy case were included into the control group. Criteria in the ESSG and B. Amor sets were looked for in the patient and control groups. The frequency of spondylarthropathy meeting each criteria set was determined. RESULTS: Of the 841 patients evaluated during the study period, 68 met B. Amor's criteria and 72 met ESSG criteria. There were 29 cases of ankylosing spondylitis (40.3%), ten of peripheral psoriatic arthritis (13.8%), two of reactive arthritis (2.8%), two of enteropathic arthropathy (2.8%), and 29 of undifferentiated spondylarthropathy (40.3%). In the definite spondylarthropathy group, sensitivity and specificity were 77.19% and 97.55% for B. Amor's criteria versus 91.23% and 100% for ESSG criteria. The frequency of spondylarthropathy was 8.1% (95% confidence interval [CI], 6.3-9.9) or 8.56% (CI 6.6-10.5) according to B. Amor and ESSG criteria, respectively. CONCLUSION: Our data validate both criteria sets in the Lebanese population, demonstrating that they are useful in populations that are genetically different from the European populations used to develop them. Spondyloarthropathy is the most common in our rheumatology practice.     

Significance of retrograde blood flow in the posterior tibial and deep plantar veins of the foot in the pathogenesis of decompensated varicose disease

The problems of enteral and parenteral nutrition of patients with gastroenteric diseases, peritonitis in early postoperative period are considered. A degree of efficiency of specialized food mixes as one of the forms of basic therapy of a number of surgical and therapeutic of diseases is shown.