Gastroesophageal reflux (GER) in infants can be secondary to food allergy. We have evaluated the frequency with which GER is associated with cow's milk protein allergy (CMPA) in infants < 1 yr old ...and tried to indicate the laboratory and instrumental examinations useful in diagnosing GER + CMPA. We studied 140 infants (60 M, 80 F), mean age 6.0 +/- 2.8 months. After 24-h esophageal pH-metry, esophageal endoscopy, and elimination diet, followed by a double-blind challenge, the patients were divided into four groups: primary GER, GER secondary to CMPA, CMPA without GER, and a control group with subjects suffering from neither GER nor CMPA. Thirty of 72 patients with GER were also suffering from CMPA. No differences were observed as regards age, sex, symptoms, and clinical or family history between patients with GER only and those with GER + CMPA. The immunological test most useful for GER + CMPA diagnosis was the IgG anti-beta-lactoglobulin assay: positive in 27/30 subjects with GER + CMPA and in 4/42 patients with GER only. We also observed a characteristic pattern of the pH-monitoring tracing in 26/30 patients with GER + CMPA but in none of the 42 patients with GER only. This consisted of a progressive, constant reduction in esophageal pH at the end of a feed, which continued up to the following feed, when pH rose steeply. We conclude that the evidence of this characteristic tracing and of a high IgG anti-beta-lactoglobulin value are specific and sensitive tests for GER + CMPA diagnosis.
Bronchiolitis obliterans syndrome (BOS) is the major cause of late graft failure after lung transplantation. The objective was to determine whether de novo donor human leukocyte antigen ...(HLA)-specific antibodies (DSA) are associated with the development of BOS or patient survival. Data were analyzed from 188 lung transplant recipients with a follow-up period up to 8 years.
HLA antibody monitoring was performed at 3-month intervals post-transplant at routine outpatient clinic attendances and during the investigation of any acute deterioration. HLA antibody data were available for 148 patients; 66 (45%) had produced HLA antibodies after transplant, of which 38 (26%) were DSA and 28 (19%) non-donor-specific HLA antibodies.
De novo DSA was associated with development of BOS Stage 1 (BOS1; hazard ratio HR = 2.302, p = 0.0015), BOS2 (HR = 3.627, p < 0.0001) and BOS3 (HR = 5.736, p < 0.0001). De novo persistent DSA correlated strongly with shorter time to onset of BOS3 (HR = 6.506, p = 0.0001). There was a significant reduction in patient survival associated with de novo DSA (HR = 1.886, p = 0.047). In multivariable analyses, de novo DSA was an independent predictor for development of all stages of BOS as well as an independent predictor of poor patient survival.
De novo DSA is a major risk factor for progression to BOS and shorter patient survival. Treatments to remove antibodies or limit antibody-mediated damage could be considered when DSA are first detected. However, a randomized, controlled trial of treatment options would enable a clearer understanding of the benefits, if any, of antibody-removal therapies.
Abdominal ultrasound has shown a frequent association between abdominal lymphadenopathy (LA) and chronic liver disease, but contradictory data have been reported on its relationship with the main ...parameters of hepatic function. The aim of this study was to correlate the prevalence of LA in patients who were chronic hepatitis-anti-hepatitis C virus positive prospectively followed-up over the last 3 years and its relationship with biochemical and histological data.
136 RIBA II confirmed positive patients with ALT levels >2N were included. None of these had been or was at the time of study on interferon treatment. Ultrasound was performed using a Toshiba SSA 240 A apparatus with a 3.75 MHz convex probe; the operator was unaware of the other results. Diagnosis of chronic hepatitis in all cases was made on biopsy specimens; the histological activity index (HAI) score, according to Knodell, and the grading (G) and staging (S) scores, according to Desmet, were also evaluated.
LA was found in 54 out of 136 patients (40%); accordingly, patients were divided into two groups: the LN + ve group included 54 patients (M 33, mean age 48.1+/-11.7 yr) and the LN-ve group included 82 patients (M 69, mean age 45.3+/-11.9 yr). LN + ve patients showed significantly higher serum levels of AST (p < 0.0005), ALT (p < 0.001), gammaGLO (p < 0.05) and gammaGT (p < 0.02) than LN - ve patients. There was a more severe degree of liver disease in LN + ve patients, expressed by the higher HAI (p < 0.002), G (p < 0.002), and S (p < 0.005). The chi2 test for linear association analysis confirmed the trend toward greater histological severity in LN + ve patients (chi2 MH = 10.2; p < 0.002). Logistic regression confirmed the association between the presence of LA and AST (p < 0.02), ALT (p < 0.03), G (p < 0.02), and S (p < 0.02).
This study showed a moderate prevalence of LA in chronic hepatitis C, lower than that reported in other studies. LA was associated with serum parameters of cytolysis, and above all, with the severity of histological damage.
Following the discovery of hepatitis C virus, more liver biopsies (LB) than before are being performed to assess the severity of liver disease. In this study, following the recommendations for ...outpatient LB made by the Patient Care Committee of the American Gastroenterological Association, we assessed the feasibility and benefits of LB performed as an outpatient versus inpatient procedure over the last 7 years in our centre. The study included 1,581 patients consecutively examined in our institute; all LBs were performed by a single operator with a 16-gauge needle using the Menghini technique, and in all cases the puncture site was determined using prebiopsy ultrasound. Liver lesions were classified using grading and staging scores. Ultrasound-guided LB of focal lesions were excluded from this study. LB was performed on 1,318 outpatients and 263 hospitalized patients. The mean age of the hospitalized patients was higher than that of the outpatients (p < 0.0001). As major side effects, one death and one haemoperitoneum requiring blood transfusion were recorded in the hospitalized patients. As minor side effects, one haemorrhage occurred in the hospitalized patients, whereas a case of haemobilia and 2 cases of subcapsular haematoma were recorded in the outpatients. In both groups pain at the puncture site was the most frequent minor complication which easily resolved after non-steroid drug administration. Severe histological diagnoses, both in terms of grading and staging, were significantly associated with hospitalized patients. In conclusion, by carefully selecting patients and using prebiopsy ultrasound to assess the puncture site, outpatient LB can be safely performed in most cases; this procedure should be more widely used, because it has met with the favour of patients who are able to return home the same day and reduces public health care service costs.
Nutrients malabsorption frequently occurs in human immunodeficiency virus (HIV)-infected patients, but very few studies have investigated exocrine pancreatic digestive capacity in these patients. We ...therefore evaluated the frequency of exocrine pancreatic impairment and its eventual relation with fat malabsorption in HIV-infected patients.
Thirty-five HIV-infected patients (30 male, 5 female: mean age +/- standard deviation, 33.6 +/- 7.2 years) and 51 sex- and age-matched controls without gastroenterologic diseases were studied. In all subjects fecal elastase 1 (EL-1) was assayed, and fecal fat excretion was evaluated with the steatocrit test.
Nineteen of 35 (54%) HIV-infected patients showed subnormal EL-1 values, whereas all the controls had normal values; furthermore, EL-1 values were significantly lower in patients than in controls: mean (95% confidence intervals), 207 ( 164-251 ) microg/g versus 312 (291-332) microg/g (P < 0.0001). Increased fecal fat excretion was observed in almost all (25 of 35) HIV-infected patients, and an inverse but not significant correlation was found between fecal EL-1 and steatocrit values. No association was found between reduced fecal EL-1 and the severity of HIV disease or nutritional and immunologic status. Opportunistic infections and drug administration had no influence on EL-1 concentrations in stools.
Reduced exopancreatic function is frequent in HIV-infected patients but does not seem to be a major factor contributing to fat malabsorption.
This study was designed to assess patients with chronic hepatitis C (CHC) for the presence of thyroid autoimmunity and dysfunction, to evaluate the risk of thyroid disorders associated with ...interferon (IFN) therapy, and to survey the outcome of possible treatment-related thyroid injury. Out of 104 consecutive untreated patients (30 women and 74 men; mean age, 52.7 years), 8 (7.7%) were found seropositive for thyroid autoantibodies (ThyAb), whereas seropositivity in healthy controls was 1/98 (1.3%). The relative increase in risk of developing thyroid autoimmunity associated with CHC was 760% (95% CI, 220-1300%). No patients had abnormalities of thyroid function tests, but on IFN treatment, 3/3 patients showed a rapid over-range rise in circulating thyrotropin, which returned to normal after therapy discontinuation. In the other 5 seropositive patients who refused treatment, thyroid function remained normal. Out of the 58 initially seronegative patients who consented to IFN treatment, 9 (15.5%) developed thyroid autoimmunity. Seven of them (77.7%) had thyroid dysfunction: hypothyroidism in 4 cases, transient thyrotoxicosis in 2 cases. The last patient developed TSH-receptor antibodies and Graves' disease, requiring methimazole therapy. Thyroid function recovered in the former 6 cases following IFN discontinuation. In the 28 initially seronegative patients who refused IFN and participated in a preliminary tauroursodeoxycholic acid trial, antithyroglobulin antibodies alone appeared in one case, but no thyroid dysfunction was observed. The relative risk of thyroid autoimmune disorder associated with IFN therapy was 342% (28-636%). The patients with CHC were unlikely to develop thyroid dysfunction in the absence of IFN therapy, in spite of being ThyAb seropositive. Moreover, a considerable proportion of seronegative patients, when IFN-treated, developed thyroid autoimmunity and then thyroid dysfunction. Both in seropositive and seronegative patients immediate IFN discontinuation normalized thyroid function and hormone replacement therapy was not necessary.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The impact of Luminex-detected HLA antibodies on outcomes after lung transplantation is unclear. Herein we have undertaken a retrospective study of pre-transplant sera from 425 lung transplants ...performed between 1991 and 2003.
Pre-transplant sera, originally screened by complement-dependent cytotoxicity (CDC) assays, were retrospectively tested for the presence of HLA-specific antibodies using HLA-coated Luminex beads and C4d deposition on Luminex beads. The results were correlated with graft survival at 1 year.
Twenty-seven patients were retrospectively identified as having been transplanted against donor-specific HLA antibodies (DSA) and 36 patients against non-donor-specific HLA antibodies (NDSA). DSA-positive patients had 1-year survival of 51.9% compared with 77.8% for NDSA and 71.8% for antibody-negative patients (p = 0.029). One-year survival of patients with complement-fixing DSA was 12.5% compared with 62.5% for non-complement-fixing DSA, 75.8% for non-complement-fixing NDSA and 71.8% for antibody-negative patients (p < 0.0001). DSA-positive patients with mean fluorescence intensity (MFI) >5,000 had 1-year survival of 33.3% compared with 71.4% for MFI 2,000 to 5000 and 62.5% for MFI <2,000 (p = 0.0046). Multivariable analysis revealed DSA to be an independent predictor of poor patient survival within 1 year (p = 0.0010, hazard ratio HR = 3.569) as well as complement-fixing DSA (p < 0.0001, HR = 11.083) and DSA with MFI >5,000 (p = 0.0001, HR = 5.512).
Pre-formed DSA, particularly complement-fixing DSA, and high MFI are associated with poor survival within the first year after lung transplantation. Risk stratification according to complement fixation or MFI levels may allow for increased transplantation in sensitized patients.
Growing evidence indicates that lysosomal Cathepsins D (CD), B (CB) and L (CL) may promote carcinogenesis and tumor progression. Therefore, we evaluated their potential value as biochemical ...parameters of malignant progression in patients with benign diseases which may undergo malignant transformation, such as liver cirrhosis (LC) and chronic pancreatitis (CHP) as well as in hepatocellular carcinoma (HCC) and pancreatic cancer (DPC). CD, CB and CL serum levels were determined by immunoenzymatic assays in LC, CHP, HCC or DPC patients and correlated with a number of biochemical and clinical parameters of these diseases. CD serum levels were increased in LC, CHP and HCC, but not in the DPC group as compared to normal subjects (NS) (P < 0.01). Interestingly, higher levels of this enzyme were observed in LC patients compared to HCC patients ( P < 0.01). CB serum concentrations were increased in all patient groups (P < 0.01). However no difference was evidenced between benign and malignant diseases. CL serum levels were significantly increased only in DPC as compared to NS (P < 0.01) or CHP patients (P < 0.02) and in HCC as compared to NS (P < 0.01). The evaluation of CD, CB and CL serum pattern in LC, CHP, HCC and DPC patients may be useful as additional biochemical parameters in the differential diagnosis and therapeutic monitoring of these diseases. Prospective clinical investigations to assess the potential value of these enzymes as biochemical markers of malignant progression of LC or CHP are warranted by the present data.
Background: The possibility of assaying antiendomysial antibodies (EmA) on the human umbilical cord instead of monkey esophagus has recently been suggested. We therefore evaluated in patients with ...celiac disease (CD) the sensitivity and specificity of EmA and of antigliadin antibodies (AGA) for both umbilical cord and monkey esophagus. Methods: We studied 36 patients with CD and atrophy of the intestinal mucosa (median age, 1.4 years), 14 patients with CD on gluten-free diet for 8-12 months (median age, 3.0 years), 36 controls without gastrointestinal disease (median age, 4.0 years), and 72 patients with cow's milk protein enteropathy (CMPE) (median age, 1.2 years). AGA and EmA on monkey esophagus were assayed with commercially available kits; the slides with umbilical cord were prepared in our laboratory. Results: There was a perfect concordance between EmA results evaluated on umbilical cord and those on monkey esophagus; there was a doubtful result in only one case on human umbilical cord, which was positive with low liter on monkey esophagus. EmA specificity was 100%; the specificity of AGA IgG varied between 72% and 94% and of AGA IgA between 90% and 100% depending on whether controls without gastrointestinal disorders or patients with CMPE were considered. EmA sensitivity was 97%, AGA IgG was 89%, and AGA IgA 72% sensitive. The only false negative for EmA was positive for AGA IgG and AGA IgA. Conclusions: Using human umbilical cord as a substrate for EmA may provide the same sensitivity and specificity as offered by the test using monkey esophagus substrate, thus reducing costs and avoiding the use of endangered species.
Anti-endomysial antibodies (EmA) have been shown to have a high specificity and sensitivity in celiac disease (CD) diagnosis, and their use is considered effective in improving the diagnostic ...accuracy of CD screening.
To report the clinical details of transient IgA EmA positivity in a patient with Graves' disease.
We screened 48 patients (7 males, age range 19-79, median 58.3 years) for CD. They were hospitalized for thyroid disorders (30 patients had autoimmune hypothyroidism and 18 had Graves' disease with clinical hyperthyroidism associated with diffuse goitre). CD screening was carried out on all patients by assaying serum anti-gliadin antibodies (AGA) and EmA.
None of the 48 patients in our study were positive for IgA and/or IgG-class AGA and none showed IgA deficiency. Only 1 patient was positive for EmA; however, intestinal biopsy in this subject was normal both when thyroiditis was first diagnosed and subsequently after 2 and 3 years. Furthermore, EmA became negative after 2 years. New gastroenterological investigations performed 3 years after the diagnosis confirmed the normal intestinal histology and absorption capacity. Moreover, AGA, EmA and tissue transglutaminase antibodies were negative.
This study underlines the possibility of transient EmA positivity without any signs of CD in patients with autoimmune thyroid disorders.
PDF
