CD163L1+CXCL10+ Macrophages are Enriched Within Colonic Lamina Propria of Diverticulitis Patients.

BACKGROUND: Inflammation of diverticula, which are outpouchings of the colonic bowl wall, causes diverticulitis. Severe cases of diverticulitis require surgical intervention. Through RNA-seq analysis of intestinal tissues, we previously found that the innate immune response was deregulated in surgical diverticulitis patients. In that study, pro-inflammatory and macrophage markers were differentially expressed in the colons of diverticulitis versus control patients. Here we investigate CD163L1+ macrophages and the pro-inflammatory chemokine, CXCL10, in diverticulitis. MATERIALS AND METHODS: We assessed tissue from an uninvolved area adjacent to a region of the sigmoid colon chronically affected by diverticulitis and performed Spearman's correlation on transcripts associated with macrophage signaling. We identified altered CD163L1 and CXCL10 gene expression levels that we confirmed by RT-qPCR analysis on an independent cohort of diverticulitis patients and controls. We used immunofluorescence microscopy to localize CD163L1+ macrophages and CXCL10 levels in intestinal tissue and ELISA to measure CXCL10 levels in patient serum. RESULTS: We found a positive correlation between intestinal CD163L1 and CXCL10 gene expression and an increased number of CD163L1+ macrophages in the sigmoid colons of diverticulitis patients relative to controls (P = 0.036). Macrophages at the apices of colonic crypts expressed the chemokine CXCL10. Correspondingly, these diverticulitis patients also displayed heightened CXCL10 levels in their serum (P = 0.007). CONCLUSIONS: We identified a novel population of CD163L1+CXCL10+ macrophages in the colonic crypts of diverticulitis patients and demonstrated increased expression of serum CXCL10 in these patients. CXCL10 may serve as a prognostic biomarker to aid in clinical decision making for diverticulitis patients.

Diagnostic and prognostic significance of inflammatory parameters in acute diverticulitis: A retrospective cohort study.

BACKGROUND: The optimum biochemical or hematological marker to determine diagnosis and severity of acute diverticulitis has not been established. We aimed to compare the utility of hematological parameters in the diagnosis and severity of acute diverticulitis. METHODS: Sixty-nine patients in diverticular disease (acute diverticulitis and diverticulosis subgroups) and 36 patients in control group were included in the study. The biochemical analysis performed at the time of diagnosis included white blood cell, mean platelet volume, neutrophil count, platelet count (PLT), C-reactive protein, and calculation of neutrophil count/lymphocyte and PLT/lymphocyte ratios. Patients in the diverticulitis group were divided into four stages according to the Hinchey classification based on abdominal CT findings. RESULTS: The mean platelet-lymphocyte ratio in the diverticulitis and diverticulosis groups was significantly lower than that in the control group (p<0.05). The best sensitivity and specificity values to distinguish acute diverticulitis and diverticulosis were 63.64% and 72.22% for the neutrophil-lymphocyte ratio (NLR) at a cutoff value of 2.78 and above and 30.30% and 86.11% for the platelet-lymphocyte ratio at a cutoff value of 87.46 and above. The diagnostic accuracy rates to distinguish between the diverticulitis and the control groups that the best sensitivity and specificity values were found to be NLR at a cutoff value of 11.55 and above and 100% and 100% for the platelet-lymphocyte ratio at a cutoff value of 12.28 and above. The NLR values were significantly lower in patients with Hinchey Stage 1 disease than those in patients with Stages 2 and 3 disease (respectively, p=0.003 and p=0.006). CONCLUSION: NLR and platelet-lymphocyte ratio can serve as useful biomarkers for the differential diagnosis and severity in acute diverticulitis.

Can initial inflammatory markers predict length of stay in uncomplicated diverticulitis?

AIM: To investigate the ability of White Cell Count (WCC), Neutrophil count & C-Reactive Protein (CRP) levels at admission to predict length of stay (LOS) in patients with uncomplicated diverticulitis. METHOD: This study was performed as a retrospective review of all patients admitted with CT proven uncomplicated diverticulitis over a one-year period. WCC, Neutrophils and CRP levels where recorded at admission. Uniform discharge criteria where used and length of stay measured. A correlation analysis was performed between the inflammatory markers and LOS. RESULTS: A total of 84 admissions with uncomplicated diverticulitis was included in this study. Average LOS 3.06 (range 1-7 days). On Romaadmission average CRP was 55 (1-276), WCC 11.5 (4.5-35.6) and Neutrophils 8.37 (2.3-18.9). Peak inflammatory values were also measured with mean peak CRP 93.5 (3-325), WCC 11.6 (5.1-35.6) and neutrophils 8.47 (2.3-18.9). Inflammatory markers were correlated to LOS. Multivariate analysis and Fit Plots showed no correlation between any of the inflammatory markers and LOS. Using a modified Hinchey classification 8 patients were Hinchey 0, 60 Hinchey Ia and 16 Hinchey Ib. Hinchey classification was associated with longer LOS (Hinchey 0 mean LOS 2.63 days, Hinchey Ia 2.71 days, Hinchey Ib 4.4 days). CONCLUSION: There was a high degree of variation in the inflammatory markers at admission, as well as the peak level of these inflammatory markers during the patients stay. The extent to which these markers were raised did not correlate with the patients' length of stay. As such, the use of inflammatory markers has limited prognostic value in patients with uncomplicated diverticulitis.

Is there a role for procalcitonin in differentiating uncomplicated and complicated diverticulitis in order to reduce antibiotic therapy? A prospective diagnostic cohort study.

AIMS OF THE STUDY: While studies show that antibiotic treatment for uncomplicated diverticulitis seems to have no benefit, most experts advocate antimicrobial therapy for complicated diverticulitis. However, even for uncomplicated diverticulitis, most clinicians are very reluctant to withhold antibiotics. Biomarkers could help to guide antibiotic therapy as this approach has been shown to be effective for acute respiratory infections. In this diagnostic cohort study we evaluated whether procalcitonin could be a biomarker to distinguish complicated from uncomplicated cases of diverticulitis. METHODS: Complicated diverticulitis was defined as having abscess formation or perforation diagnosed by abdominal computed tomography (CT) scan. In all patients with suspected diverticulitis, procalcitonin values were measured at admission and on day 2. These values were blinded for clinicians, and treatment was carried out according to the physician's judgement. Two groups (complicated vs uncomplicated diverticulitis) were defined. Patients who had received antibiotic treatment before admission were excluded. Difference in procalcitonin values was calculated for both groups using the Mann-Whitney test. Receiver operating characteristics (ROC) were calculated to determine cut-off values for procalcitonin according to the gold standard (abdominal CT scans). RESULTS: 115 patients were included for analysis. 35 patients (30%) suffered from complicated diverticulitis. The median procalcitonin value for uncomplicated diverticulitis was significantly lower compared to complicated diverticulitis (median 0.05, interquartile range [IQR] 0.05-0.06 ng/l vs median 0.13, IQR 0.05-0.23 ng/l; p <0.0001). In the ROC analysis, the sensitivity and specificity were 81% and 91% when the highest procalcitonin value (days 1 and 2) was considered, with a cut-off value of 0.1 ng/l. CONCLUSION: Procalcitonin was able to differentiate with a high sensitivity and specificity between complicated and uncomplicated cases of diverticulitis when combined with abdominal CT scans. As most clinicians still treat uncomplicated diverticulitis with antibiotics, procalcitonin could be an interesting parameter for guiding therapy and decreasing antibiotic usage. This should be further evaluated in randomised trials.

Delta neutrophil index as a promising prognostic marker of emergent surgical intervention for acute diverticulitis in the emergency department.

BACKGROUND: Early identification of patients with acute diverticulitis who require emergent surgical intervention in the emergency department (ED) is important to the physician. Although computed tomography (CT) has an important role in evaluating the severity of diverticulitis, its findings alone may not predict the need for emergent surgical intervention in all patients with acute diverticulitis in the ED. Serum inflammation markers may help to differentiate severity of acute diverticulitis and predict the need for surgical intervention in clinical practice. No information is currently available on the clinical usefulness of the delta neutrophil index (DNI), with respect to the prediction of emergent surgical intervention in patients with acute diverticulitis at the ED. METHODS: This was a retrospective observational study of consecutive adult patients with acute diverticulitis confirmed by CT in the ED, between January 2014 and December 2016. Recruited patients were divided into two groups: emergent surgical intervention and no surgical intervention. The following laboratory serum parameters were examined in the ED: DNI value, C-reactive protein (CRP) levels, white blood cell count, neutrophil count, and neutrophil-to-lymphocyte ratio (NLR). The patients were also examined for the presence or absence of complications by CT. RESULTS: A total of 132 patients were finally included in the study, with the emergent surgical intervention group constituting 52 patients. The median DNI value, CRP levels, neutrophil count, and NLR were significantly higher in the emergent surgical intervention group than in the no surgical intervention group. The area under the curve for predicting emergent surgical intervention, using the DNI was significantly higher than that of CRP levels, neutrophil count, or NLR. Moreover, the combination of initial DNI and CT was most powerful diagnostic modality. CONCLUSIONS: DNI values measured at the ED combined with CT were good predictors for emergent surgical intervention in acute diverticulitis. If the DNI value is greater than 0.7% and complications in CT are suspected in patients suspected to have acute diverticulitis, the need for emergent surgical intervention should be considered carefully in the ED.

Uncomplicated Acute Diverticulitis: Identifying Risk Factors for Severe Outcomes.

BACKGROUND: The management of uncomplicated (Modified Hinchey Classification Ia) acute diverticulitis (AD) has become increasingly conservative, with a focus on symptomatic relief and supportive management. Clear criteria for patient selection are required to implement this safely. This retrospective study aimed to identify risk factors for severe clinical course in patients with uncomplicated AD. MATERIALS AND METHODS: Patients admitted to General Surgery at two New Zealand tertiary centres over a period of 18 months were included. Univariate and multivariate analyses were carried out in order to identify factors associated with a more severe clinical course. This was defined by three endpoints: need for procedural intervention, admission >7 days and 30-day readmission; these were analysed separately and as a combined outcome. RESULTS: Uncomplicated AD was identified in 319 patients. Fifteen patients (5%) required procedural intervention; this was associated with SIRS (OR 3.92). Twenty-two (6.9%) patients were admitted for >7 days; this was associated with patient-reported pain score >8/10 (OR 5.67). Thirty-one patients (9.8%) required readmission within 30 days; this was associated with pain score >8/10 (OR 6.08) and first episode of AD (OR 2.47). Overall, 49 patients had a severe clinical course, and associated factors were regular steroid/immunomodulator use (OR 4.34), pain score >8/10 (OR 5.9) and higher temperature (OR 1.51) and CRP ≥200 (OR 4.1). CONCLUSION: SIRS, high pain score and CRP, first episode and regular steroid/immunomodulator use were identified as predictors of worse outcome in uncomplicated AD. These findings have the potential to inform prospective treatment decisions in this patient group.

Do Inflammatory Indices Play a Role in Distinguishing between Uncomplicated and Complicated Diverticulitis?

BACKGROUND: The usefulness of inflammatory indices in assessment of the severity of acute diverticulitis remains unestablished. The aim of this study was to determine whether inflammatory indices and hematological ratios could be utilised to differentiate between uncomplicated and complicated diverticulitis. METHODS: Hematological and inflammatory indices were recorded for each admission with CT confirmed acute diverticulitis (101 complicated, 127 uncomplicated). Cases were divided into training (n = 57) and test sets (n = 171). A classification and regression tree (CART) analysis was employed in the training set to identify optimal inflammatory marker cut-off points associated with complicated diverticulitis. Samples (test set) were then categorized as (A) greater than and (B) less than CART identified cut-off points. The predictive properties of inflammatory marker cut-off points in distinguishing severity of diverticulitis were assessed using a univariate logistic regression analysis, summary receiver operating characteristic curves and confusion matrix generation. RESULTS: C-reactive protein >109 mg/ml (OR 3.07, 95% CI 1.43-6.61, p = 0.004, area under the curve; AUC = 0.64) and white cell lymphocyte ratio (WLR) >17.72 (OR 4.23, 95% CI 1.95-9.17, p < 0.001, AUC = 0.64) were the most accurate parameters in distinguishing complicated and uncomplicated disease. WCC >21 × 109/l (p = 0.02, AUC = 0.60) and lymphocyte count >0.55 × 109/l (p = 0.009, AUC = 0.60) were less accurate. CONCLUSION: Widely used inflammatory indices are useful in the depiction of complicated diverticulitis. The indices cut-off points highlighted in this study should be considered at the time of diagnosis in combination with radiological features of complicated diverticulitis.

Effect of oral mesalamine on inflammatory response in acute uncomplicated diverticulitis.

AIM: To evaluate the impact of mesalamine administration on inflammatory response in acute uncomplicated diverticulitis. METHODS: We conducted a single centre retrospective cohort study on patients admitted to our surgical department between January 2012 and May 2014 with a computed tomography -confirmed diagnosis of acute uncomplicated diverticulitis. A total of 50 patients were included in the analysis, 20 (study group) had received 3.2 g/d of mesalamine starting from the day of admission in addition to the usual standard treatment, 30 (control group) had received standard therapy alone. Data was retrieved from a prospective database. Our primary study endpoints were: C reactive protein mean levels over time and their variation from baseline (ΔCRP) over the first three days of treatment. Secondary end points included: mean white blood cell and neutrophile count over time, time before regaining of regular bowel movements (passing of stools), time before reintroduction of food intake, intensity of lower abdominal pain over time, analgesic consumption and length of hospital stay. RESULTS: Patients characteristics and inflammatory parameters were similar at baseline in the two groups. The evaluation of CRP levels over time showed, in treated patients, a distinct trend towards a faster decrease compared to controls. This difference approached statistical significance on day 2 (mean CRP 6.0 +/- 4.2 mg/dL and 10.0 +/- 6.7 mg/dL respectively in study group vs controls, P = 0.055). ΔCRP evaluation evidenced a significantly greater increment of this inflammatory marker in the control group on day 1 (P = 0.03). A similar trend towards a faster resolution of inflammation was observed evaluating the total white blood cell count. Neutrophile levels were significantly lower in treated patients on day 2 and on day 3 (P < 0.05 for both comparisons). Mesalamine administration was also associated with an earlier reintroduction of food intake (median 1.5 d and 3 d, study group vs controls respectively, P < 0.001) and with a shorter hospital stay (median 5 d and 5.5 d, study group vs controls respectively, P = 0.03). CONCLUSION: Despite its limitations, this study suggests that mesalamine may allow for a faster recovery and for a reduction of inflammatory response in acute uncomplicated diverticulitis.

[Hemodialysis to remove anticoagulant dabigatran during emergencies]. / Hemodiálisis para remover el anticoagulante dabigatrán en situaciones de urgencia.

Dabigatran is an oral anticoagulant from the class of the direct thrombin inhibitors, indicated for prevention of thromboembolic events in patients with non valvular atrial fibrillation. Unlike warfarin, dabigatran has no known antidote. Hemodialysis has been suggested as a method for removing dabigatran and thereby reducing its anticoagulant effect. We report the case of a patient with a known history of atrial fibrillation, treated with dabigatran, who was admitted for emergency abdominal surgery. At six hours after the last dose received, coagulation studies were altered. In absence of an antidote to reverse its effects, it was decided to perform hemodialysis. After three hours of dialysis coagulation parameters were improved and the patient underwent surgery without showing abnormal bleeding during surgery or in the postoperative period.

Hemodiálisis para remover el anticoagulante dabigatrán en situaciones de urgencia / Hemodialysis to remove anticoagulant dabigatran during emergencies

El dabigatrán es un nuevo inhibidor directo de la trombina, de administración oral, empleado para la prevención de eventos tromboembólicos en pacientes con fibrilación auricular no valvular. A diferencia de la warfarina, no se dispone de un antídoto conocido. La hemodiálisis ha sido sugerida como un método para remover el dabigatrán y reducir el efecto anticoagulante. Se presenta el caso de un paciente con antecedente de fibrilación auricular y medicado con dabigatrán, que fue admitido en el hospital para una cirugía abdominal de urgencia. A las seis horas de la última dosis recibida, los estudios de coagulación mostraban alteración. Ante la falta de antídoto para revertir los efectos, se decidió realizar hemodiálisis. Luego de tres horas de diálisis los parámetros de coagulación tendieron a normalizarse y el paciente fue operado sin presentar hemorragias anormales durante la cirugía o en el postoperatorio.

Dabigatran is an oral anticoagulant from the class of the direct thrombin inhibitors, indicated for prevention of thromboembolic events in patients with non valvular atrial fibrillation. Unlike warfarin, dabigatran has no known antidote. Hemodialysis has been suggested as a method for removing dabigatran and thereby reducing its anticoagulant effect. We report the case of a patient with a known history of atrial fibrillation, treated with dabigatran, who was admitted for emergency abdominal surgery. At six hours after the last dose received, coagulation studies were altered. In absence of an antidote to reverse its effects, it was decided to perform hemodialysis. After three hours of dialysis coagulation parameters were improved and the patient underwent surgery without showing abnormal bleeding during surgery or in the postoperative period.

IgG4-related lacrimal sac diverticulitis.

IgG4-related disease is characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. We herein report a case of lacrimal sac diverticulitis with marked IgG4-positive plasma cell infiltration. An 89-year-old woman presenting with right lower eyelid mass. Imaging modalities demonstrated a cystic orbital mass located beneath the globe and adjacent to enlarged lacrimal sac. Serological tests showed high IgG4 and normal IgG levels, measuring 242 and 1603 mg/dl, respectively. The orbital mass was surgically excised. Histologically, the excised tissue demonstrated marked inflammation with fibrosis surrounded by mononuclear epithelial cells. A variety of IgG and IgG4-positive plasma cells infiltrated the stroma. This patient was diagnosed as an IgG4-related lacrimal sac diverticulitis, based on current diagnostic criteria of IgG4-related disease. It is likely that IgG4-related inflammation occurs in a lacrimal sac diverticulum, which should be considered a differential diagnosis in inferior orbital tumors.

Randomized controlled trial of oral vs intravenous therapy for the clinically diagnosed acute uncomplicated diverticulitis.

OBJECTIVE: Despite the high prevalence of hospitalization for left iliac fossa tenderness, there is a striking lack of randomized data available to guide therapy. The authors hypothesize that an oral antibiotic and fluids are not inferior to intravenous (IV) antibiotics and 'bowel rest' in clinically diagnosed acute uncomplicated diverticulitis. METHOD: A randomized controlled trial was constructed in two District General Hospitals. All clinically diagnosed patients presenting with acute uncomplicated diverticulitis were eligible for the study. Oral and IV regimens utilizing ciprofloxacin and metronidazole were compared. The primary outcomes studied were surrogates for resolution of symptoms (including tenderness on day 3 and length of stay) and failure of oral therapy. Secondary endpoints studied were serial constitutional and biomarker trends. RESULTS: There were 41 patients in the oral arm and 38 in the IV arm (n = 79). No patient had to be converted to IV antibiotics from the oral group. There was a complete resolution of symptoms in both groups. Tenderness was equivalent in both groups on day 3. Among secondary endpoints, a serial decrease in C reactive protein was the best serological predictor of resolution for both groups. CONCLUSION: Oral antibiotics are not inferior to intravenous antibiotics in achieving resolution of clinically diagnosed diverticulitis.

The severity of infection induces a shift in the type 1/Type 2 T-helper cell balance in patients with or without peritonitis.

BACKGROUND: A type-1 to type-2 T-helper cell (Th1/Th2) shift is hypothesized to occur among patients with severe trauma and pancreatitis. It was hypothesized that the Th2 situation caused an immune-suppressed period that led to a critical imbalance in the patients' conditions, with an increased risk of multiple organ failure and mortality. METHODS: In eight patients with localized intra-abdominal infection (diverticulitis) and six patients with peritonitis due to perforation of a hollow viscus, we examined the cytokine response of CD3(+) T cells in the greater omentum and in the peripheral blood by in vitro stimulation, intracellular cytokine staining, and flow cytometry for TNF-alpha, IFN-gamma, IL-2, and IL-4. Follow-up cytokine assays were carried out on peripheral blood on days 3 and 7. Different levels of cytokine expression in each group were examined to determine the origin of the lymphocytes, both from omentum or peripheral blood. Cytokine production in the diverticulitis group was compared with that of the peritonitis patients. RESULTS: In localized infections (diverticulitis), there was higher expression of TNF-alpha (51%/35% positive cells in omentum/blood), IFN-gamma (47%/32%), and IL-2 (33%/20%) in the omentum than in the peripheral blood mononuclear cells (PMBCs), but this was not true for IL-4 expression (0.8%/1.3%). In patients with peritonitis, there were no differences in cytokine expression between lymphocytes from the greater omentum and from PMBCs for TNF-alpha (18%/21% omentum/blood), IFN-gamma (20%/22%), IL-2 (16%/12%), or IL-4 (10.9%/7.6%). Compared to the diverticulitis group, patients with peritonitis showed reduced expression for TNF-alpha, IFN-gamma, and IL-2, but there was a significantly higher response for IL-4 for both compartments. CONCLUSIONS: There was a shift from Th1 to Th2 in patients with severe clinical symptoms of peritonitis. Immune suppression is evident because of the T cell response in the greater omentum, but immunosuppression seems to not reach its maximum level before day 7 post operation. This differs from findings in multiple trauma and pancreatitis; however, it is parallel to the clinical situation in patients with peritonitis.

Low plasma protein Z levels in patients with ischemic colitis.

Hypercoagulable states have been suggested to play an important role in the pathogenesis of ischemic colitis. Since protein Z is, as recently demonstrated, important in the regulation of coagulation, we investigated the plasma levels of protein Z in connection to factor V Leiden (FVL) and anti-phospholipid antibodies in patients with a definite diagnosis of ischemic colitis. The plasma levels of protein Z were measured using a commercially available enzyme-linked immunosorbent assay in 33 patients with ischemic colitis, 13 patients with diverticulitis, and 33 healthy controls. Mean plasma protein Z levels were 1.38 +/- 0.52 microg/ml in patients with ischemic colitis and were significantly lower compared to healthy controls (1.86 +/- 0.49 microg/ml) and patients with diverticulitis (1.72 +/- 0.53 microg/ml) (P = 0.001). Protein Z deficiency was found in patients cases with ischemic colitis (18.2%) compared to one with diverticulitis (7.7%) and one healthy control (3.0%). In conclusion, our results suggest that low plasma protein Z levels may play a role in the disease development in some cases with ischemic colitis.

Significance of diminished factor XIII in Crohn's disease.

OBJECTIVE: Coagulation factor XIII is a plasma transglutaminase involved in crosslinking of fibrin, the last step of the coagulation system and a connective tissue factor contributing to the wound healing process. It circulates as a heterotetrameric molecule consisting of two identical proenzyme subunits (factor XIIIA) and two carrier protein subunits (factor XIIIS). The aim of this study was to determine the disease features associated with the diminution of factor XIII in Crohn's disease. METHODS: Factor XIIIA and factor XIIIS levels were assessed in patients presenting with Crohn's disease, ulcerative colitis, infectious colitis, or diverticulitis, in patients with rheumatoid arthritis, and in control subjects. Prothrombin fragment 1 + 2 assay, as a marker of the generation of thrombin and measurement of C-terminal telopeptide of type I collagen as an estimate of degradation of collagen type I, were performed. RESULTS: Factor XIIIA was significantly decreased in Crohn's disease, in ulcerative colitis, and in infectious colitis by comparison with subjects presenting with diverticulitis, normal, and rheumatoid subjects p = 0.0001). Factor XIIIS was unmodified in patients with Crohn's disease by comparison with controls but was reduced in those presenting with intestinal bleeding (p = 0.0002). In Crohn's disease, the lowest level of factor XIIIA was observed in patients with intestinal bleeding (p = 0.0003). Factor XIIIA was correlated with the Van Hees index (r = -0.5661; p = 0.0001) and with the C-terminal telopeptide of type I collagen (r = -0.4110; p = 0.0011) but not with prothrombin fragment 1 + 2. The multiple regression analysis showed that only Van Hees index and intestinal bleeding were independent variables for explaining the diminution of Factor XIIIA in Crohn's disease. CONCLUSIONS: Factor XIIIA subunit is an indicator of Crohn's disease activity. Our study suggests that a low factor XIIIA level is related to the presence of intestinal lesions and might be linked to intestinal repair mechanisms; loss in intestinal lumen could be also involved, especially in patients with intestinal bleeding.

Persistent clonal expansions of peripheral blood CD4+ lymphocytes in chronic inflammatory bowel disease.

It is increasingly recognized that chronic Ag exposure may lead to clonal expansions of T cells, including those within the peripheral blood. Inflammatory bowel disease is a chronic, multisystemic disease of unknown origin that predominantly affects the intestine. We sought to determine whether clonal expansions of T cells are present in the peripheral blood of patients with inflammatory bowel disease by an examination of TCR usage. Positively selected CD4+ and CD8+ peripheral blood T cells were isolated from subjects with active ulcerative colitis, Crohn's disease, and diverticulitis and from normal controls. Analysis of complementarity determining region 3 lengths of 24 TCR-beta chain V region families from CD4+ and CD8+ peripheral blood T cells showed a skewed distribution in the three inflammatory groups, consistent with expansion of T cell clones, in comparison to the normally distributed pattern observed among the control donors. Random sequencing of the PCR amplification products of CD4+ peripheral blood T cells from the subjects with ulcerative colitis, Crohn's disease, and diverticulitis revealed reiterative TCR-beta chain sequences that were not found in the normal donors. In subjects with Crohn's disease, the reiterative TCR-beta chain sequences from the CD4+ peripheral blood T cells were persistent over at least a 1-yr period. The persistently expanded TCR-beta chain sequences of CD4+ peripheral blood T cells were identifiable in genomic DNA isolated from archival tissue of intestine from subjects with Crohn's disease and ulcerative colitis by Southern blotting and direct DNA sequencing. An identical twin pair, concordant for Crohn's disease, shared the same reiterative TCR-beta chain sequences in their CD4+ peripheral blood T cells. These studies show that chronic intestinal inflammation is associated with expansions of CD4+ peripheral blood T cells. Furthermore, in inflammatory bowel disease these T cell clonal expansions are persistent and shared among HLA-identical individuals, implicating a response to specific, persistent, and stimulating Ags in these diseases.

Peptide YY abnormalities in gastrointestinal diseases.

Plasma concentrations of peptide YY (PYY), a newly isolated peptide produced by ileal and colonic endocrine cells, were measured in several groups of patients with digestive disorders after a standardized normal breakfast. Peptide YY levels were found to be grossly elevated in patients with steatorrhea due to small intestinal mucosal atrophy (tropical sprue). Basal levels in these patients were 79 +/- 18 pM, which was nearly 10-fold higher than those seen in healthy controls (8.5 +/- 0.8 pM). Patients with steatorrhea due to chronic destructive pancreatitis also had substantially increased basal PYY levels (47.5 +/- 6.3 pM), and their postprandial response was also greater than that of normal subjects. Moderately elevated plasma PYY concentrations were seen in patients with inflammatory bowel disease and patients recovering from acute infective diarrhea. In contrast, patients with diverticular disease, duodenal ulcer, and functional bowel disease had normal PYY responses. These changes in the secretion of PYY responses. These changes in the secretion, may shed light on the physiologic role of this newly discovered peptide and on intestinal adaptation to common digestive disorders.

Endotoxinemia in renal transplant recipients.

Endotoxinemia in renal transplant recipients. In immunosuppressed renal transplant recipients a high incidence of endotoxinemia was found during chest or urinary tract infections. Although the endotoxinemia was protracted, indicating inability to eradicate the infection, yet in general the effects were benign and adverse renal damage was not seen. The Limulus gelation test has a positive contribution to make in the diagnosis of illness in transplant recipients.