Epidemiological and prognostic factors involved in upper gastrointestinal bleeding: results of a French prospective multicenter study.

BACKGROUND AND STUDY AIMS: The mortality rate from upper gastrointestinal bleeding (UGIB) remains high, at 5 % - 10 %. The aim of the current study was to describe the epidemiological characteristics, prognostic factors, and actual practice in a cohort of patients with UGIB admitted to French general hospitals. METHODS: From March 2005 to February 2006, a prospective multicenter study was conducted at 53 French hospitals. A total of 3298 patients admitted for UGIB were enrolled consecutively. Patient data were collected up to the date of discharge from hospital. RESULTS: Data were available for 2130 men and 1073 women (mean age 63 ± 18 years), one-third of whom were taking drugs that would increase the risk of UGIB. The two main causes of bleeding were peptic ulcers (38 %) and esophagogastric varices (EGV) or portal hypertensive gastropathy (24.5 %). Mean Rockall score was 5.0 ± 2.3. Endoscopy was performed on 96 % of patients (within 24 hours in 79 %), and 66 % of those with ulcers and 62.5 % of the EGV patients underwent hemostatic therapy when indicated. Rebleeding occurred in 9.9 % of the patients, and 8.3 % died. Independent predictors of rebleeding were: need for transfusion (odds ratio [OR] 19.1; 95 % confidence interval [95 %CI] 10.1 - 35.9); hemoglobin < 10 g/dL (OR: 1.7; 95 %CI 1.1 - 3.3); Rockall score (OR: 1.4 for each 1 point score increase; 95 %CI 1.0 - 1.9), systolic blood pressure < 100 mmHg (OR: 1.9; 95 %CI 1.4 - 2.5), and signs of recent bleeding (OR: 2.4; 95 %CI 1.7 - 3.5). Independent predictors of mortality were: Rockall score (OR: 2.8; 95 %CI 2.0 - 4.0), co-morbidities (OR: 3.6 for each additional co-morbidity; 95 %CI 2.0 - 6.3), and systolic blood pressure < 100 mmHg (OR: 2.1; 95 %CI 1.8 - 2.8). Rockall score, blood pressure and co-morbidities were taken as continuous variables meaning that the OR was 1.4 for every point increase, it was the same for blood pressure. CONCLUSION: UGIB still occurs mainly as a result of peptic ulcers and portal hypertension in France, and causes significant rates of mortality. There is scope for improvement via better prevention (better use of UGIB-facilitating drugs), endoscopic therapy, and management of co-morbidities.

Nephropathy caused by Chinese herbs in the UK.

The use of Chinese herbal remedies is increasing in the UK. We report the presence of a nephrotoxic compound in herb samples, which led to end-stage renal failure in two patients. We suggest that use of these products is regulated more tightly.

Abnormal mucus in cap polyposis.

BACKGROUND: Cap polyposis is a rare disease characterised by mucoid and bloody diarrhoea, with polyps covered by a cap of mucoid and fibrinopurulent exudate. The pathogenesis is not known. AIMS: To pour some light on cap polyposis pathogenesis, by examining the mucus of patients and analysing the expression of five mucin genes, MUC2, MUC3, MUC4, MUC5AC, and MUC5B. PATIENT AND METHODS: The study was performed on biopsy specimens taken from a patient with recurrent cap polyposis. Histochemical examination, electron microscopy, and mRNA in situ hybridisation were used. RESULTS: The mucus of cap polyposis differed in three respects from that of normal adult colon: abnormal ultrastructure of the mucus in the goblet cells, predominance of non-sulphated mucins, abnormal expression of the MUC4, MUC3, and MUC5AC genes. CONCLUSIONS: Most of these abnormalities have been reported for other pathological situations, suggesting that the abnormalities observed in the mucus of this patient with cap polyposis are probably secondary phenomena rather than primary. However, the mucin abnormalities detected, which reflect deregulation of the expression of three apomucin genes, abnormal glycosylation, and abnormalities of the secretion process, are also probably involved in the clinical manifestations of cap polyposis.

Long term effect of renal transplantation on dialysis-related amyloid deposits and symptomatology.

We report the five year outcome of nine patients with dialysis-related amyloid (DRA) who underwent successful renal transplantation (RT) and six patients who remained on hemodialysis (HD). Amyloid bone cysts, a radiologic feature of DRA, and scintigraphy with 123I-labeled serum amyloid P component (SAP), a specific technique for evaluating amyloid deposits in vivo, were monitored and compared with clinical features. In all HD patients there was clinical, scintigraphic and/or radiologic evidence that DRA progressed. In contrast, eight of the RT patients experienced profound early relief of DRA symptoms following transplantation that persisted throughout follow-up, despite the reduction or withdrawal of corticosteroids. Amyloid bone cysts improved in four patients and SAP scans demonstrated regression of articular amyloid in eight out of nine cases. The modest radiographic improvement suggests that amyloid is mobilized more slowly in bone cysts than elsewhere or that cystic bone is remodeled poorly. This is the first objective evidence that DRA regresses following renal transplantation, and suggests that this may contribute to the long-term relief of DRA symptoms in transplant recipients who discontinue corticosteroids.

Cap polyposis occurring in the postoperative course of pelvic surgery.

The case is reported of a 42 year old woman who presented with the characteristic clinical, sigmoidoscopic, and histological features of cap polyposis occurring in the postoperative course of pelvic surgery. Pathogenesis of cap polyposis is unknown. In this patient, abnormal colonic motility was not a likely aetiological factor as suggested in previous cases. Despite some arguments favouring an infectious origin or participation, no specific viral or bacterial agent was identified. Cap polyposis remains a poorly recognised condition, which may be confused with inflammatory bowel disease.

Prevalence of antibodies to hepatitis C in dialysis patients and transplant recipients with possible routes of transmission.

The prevalence of hepatitis C infection and possible predisposing factors was assessed in a renal unit. Of 343 patients at our renal dialysis centre, 37 (10.8%) were anti-HCV positive by a 1st-generation assay (ELISA, Ortho/Chiron) and confirmed positive in 35 (10.2%) with a 2nd-generation test (UBI, New York). Anti-HCV positivity was significantly associated with: duration of renal replacement therapy (P < 0.0001); quantity of blood transfused (P < 0.002); duration of hospital haemodialysis (P = 0.0001); duration with a functional renal transplant (P = 0.039); and aspartate aminotransferase (P < 0.0001). Logistic regression determined the following variables to be independent risk factors: duration of renal replacement therapy with a relative risk of 34.3 for 5-9 years and 87.4 when the duration was in excess of 10 years; renal transplant for less than 1 year (relative risk of 5.0); transfusion in excess of 50 units of blood (relative risk of 11.6). Clinical assessment of anti-HCV-positive patients revealed peripheral signs of chronic liver disease in 40%, hepatomegaly in 34%, and splenomegaly in 9%. This prevalence of hepatitis C infection is similar to other European and North American centres, but contrasts with low prevalence rates reported from dialysis populations in the UK. It adds further support for routine screening of blood and possibly organ donors and implementation of further infection control measures in dialysis centres.

Serum amyloid P component in chronic renal failure and dialysis.

A normal reference interval for serum amyloid P component (SAP) concentration in the serum was established in 500 healthy adult individuals (274 women, 226 men), by electroimmunoassay calibrated with standards of highly purified, isolated SAP. The mass of SAP in these was determined from the extinction coefficient of SAP at 280 nm measured here precisely for the first time by spectrophotometry and cryogenic drying. The mean (SD, range) SAP concentration was significantly lower in women: 24 mg/l (8, 8-55), compared to 32 mg/l (7, 12-50) in men (P less than 0.001). In renal insufficiency patients, 38 with chronic renal failure, 79 on hemodialysis and 66 on continuous ambulatory peritoneal dialysis, the mean values for SAP concentration were all significantly higher than normal (range of means, 39-59 mg/l in men and 35-42 mg/l in women), but did not correlate with serum creatinine, duration of dialysis or the presence of an acute phase response. The metabolism of SAP is thus altered in renal failure and is not normalized by dialysis, but it is not clear whether this is relevant to the pathogenesis of dialysis related arthropathy and amyloidosis.

Imaging of haemodialysis-associated amyloidosis with 123I-serum amyloid P component.

Long-term haemodialysis is frequently complicated by amyloid deposition in which the fibrils consist of beta 2-microglobulin. Dialysis-related amyloid disease causes extensive morbidity and has been associated with deaths in some cases. All amyloid deposits contain amyloid P component that is derived from the normal circulating protein, serum amyloid P component (SAP). We have used scintigraphic imaging after injection of 123I-labelled SAP to assess the distribution of amyloidosis in 38 patients receiving long-term haemodialysis for end-stage renal failure. There was focal localisation of tracer at all sites where histological examination confirmed amyloid deposition. Splenic uptake was seen in 12 patients, indicating splenic amyloidosis, but there was no evidence of other visceral involvement. 6 control subjects who had been dialysed for under 1.5 years showed no localisation of tracer, nor was there any uptake of 123I-labelled human serum albumin in 3 long-term dialysis patients with histologically confirmed amyloidosis and positive 123I-SAP images. Negative scans were also obtained in 5 patients who had been transplanted 0.8-2.4 years previously, despite past evidence of dialysis arthropathy (5) and histologically proven amyloidosis (4). 123I-SAP scintigraphy may be helpful as a non-invasive method for both the diagnosis and monitoring of dialysis-associated amyloidosis.

Dialysis arthropathy: a clinical, biochemical, radiological and histological study of 36 patients.

Out of a population of 97 haemodialysis patients, 36 patients with dialysis arthropathy were identified. Dialysis arthropathy is a chronic symmetrical polyarthritis which affected 97 per cent of the patients who had been undergoing cuprophane haemodialysis for more than 10 years. It commonly affected the shoulders, hips, hands, knees and wrists, worsening with time and extending to other joints. Fifty-eight per cent of the patients complained of morning stiffness and 47 per cent complained of exacerbation of shoulder pain during or after haemodialysis. Half of the patients also suffered from carpal tunnel syndrome, which recurred and was associated with a long-lasting disability. The most common radiological abnormality was periarticular bone cysts, followed by articular erosions and a destructive spondyloarthropathy, but clinical symptoms were more common than radiological signs. Patients with dialysis arthropathy had a higher C-reactive protein level than patients without arthropathy (18.6 mg/l versus 11.4 mg/l), indicative of an inflammatory process. Some of the clinical manifestations of the disease correlated with levels of C-reactive protein and ferritin. Serum ferritin levels correlated strongly with the units of blood transfused in the past five years (RS = 0.83), and the logarithm of ferritin level correlated weakly with C-reactive protein (r = 0.32). Haemarthroses were documented in 19 per cent of patients. Mean serum beta 2-microglobulin was elevated in the patients with (57.3 mg/l) and without arthropathy (50.7 mg/l), and there was no difference in the parathormone or aluminium levels between these groups. Articular tissue was obtained in 25 patients; beta 2-microglobulin amyloid was present in 24. Larger deposits were present in the capsular tissue, and these appeared to replace collagen bundles in eight cases. Amyloid deposits replaced the lining layer in six cases. It is likely therefore that amyloid disrupts normal joint function by replacing normal joint tissue. Mild chronic synovitis with haemosiderin deposition were found in approximately 60 per cent of cases. These findings suggest that amyloid derived from beta 2-microglobulin has a primary role in the pathogenesis of dialysis arthropathy, but there was also evidence of inflammatory processes. It is suggested that iron overload or haemarthroses might contribute to the inflammation, but other factors, such as dialysis-related bioincompatibility reactions, may also have a role.

Ultrastructural immunogold studies of heparan sulphate proteoglycan in normal human glomeruli and glomerulonephritis.

The distribution of heparan sulphate proteoglycans (HSPG) has been investigated in normal human glomeruli, membranous glomerulonephritis, mesangial IgA disease, and anti-glomerular basement membrane disease. HSPG was localized using anti-bovine HSPG antibody and 10 nm gold-labelled secondary antibody on paraformaldehyde-fixed, Lowicryl K4M resin-embedded kidneys. HSPG was present in all glomeruli and there was a zonation of its distribution in that it was predominantly on the epithelial aspect of the glomerular basement membrane (GBM) and mesangium with little in the central regions of the mesangial matrix. In the cases of immune complex glomerulonephritis, no HSPG was found in the electron-dense deposits. These findings contrast with our previous studies using the same technique in which type IV collagen and fibronectin were found predominantly on the endothelial aspect of the GBM.

Macroglossia and amyloidoma of the buttock: evidence of systemic involvement in dialysis amyloid.

A 48-year-old male on cuprophane haemodialysis for 18 years, with a history of dialysis arthropathy and recurrent carpal tunnel syndrome developed macroglossia and bilateral buttock tumoral masses. The tongue and buttock masses were biopsied. Histology of both biopsies showed amyloid deposits of the beta 2-microglobulin (B2M) variety. Amyloidomas in the gluteal region and macroglossia have not been previously described in amyloid derived from B2M. These findings suggest that systemic B2M amyloidosis can have a similar tissue distribution to AL amyloidosis. This case also stresses the importance of inspection of the tongue, and palpation of the gluteal region for masses, in the assessment of patients with dialysis arthropathy.

Technetium-99-labelled methylene diphosphonate uptake scans in patients with dialysis arthropathy.

Patients on long-term haemodialysis suffer from dialysis arthropathy due to the deposition of dialysis amyloid. We investigated the use of 99Tc-labelled methylene diphosphonate bone scans in 17 patients as a possible in vivo diagnostic technique. In most clinically affected joints, with the exception of shoulders and hands, there was increased radioisotope uptake consistent with uptake by periarticular bone. In addition, we describe intense soft-tissue uptake around some clinically affected large joints. In contrast, control groups of patients on haemodialysis without arthropathy and patients without renal failure did not have increased uptake. A semi-quantitative scale of uptake was devised, and the following correlations were significant: pain perception and isotope uptake score in the ankles and feet, and the number of radiological lesions and isotope uptake scores in the wrists and knees. The following sites where the radioisotope might bind in the affected joints are proposed: amyloid deposits, areas of soft-tissue calcification, or areas of increased bone turnover. It is concluded that whereas the scanning technique cannot make a definite diagnosis of amyloid and, therefore, cannot be expected to supersede histological diagnosis, it is a useful adjuvant investigation, of particular importance in those patients unable or unwilling to undergo biopsy.

Impaired bacterial flora in human excluded colon.

We compared the rectal microflora of 16 patients with surgically excluded colorectum with 16 healthy controls. The cause of diversion was inflammatory bowel disease (n = 10), colon cancer (n = 3), miscellaneous (n = 3). Six patients had a diversion colitis. In the excluded colorectum, the total bacterial count was only slightly lower than controls but the variety of the flora was significantly reduced. This reduction was confined to strict anaerobes, mainly the genus Eubacterium and Bifidobacterium. Among aerobes, enterobacteria were more often isolated than in controls. This altered microflora of excluded colorectum could be involved in the mucosal damage observed in some cases.

Dialysis-associated amyloid: systemic or local?

Dialysis-associated amyloidosis has been classified as one of the local amyloidoses. To test this, we examined post-mortem tissue from 14 long-term haemodialysis patients, ten with dialysis arthropathy and four without arthropathy. Tissue was obtained from the shoulder, knee, or hip joints and the following organs: brain, kidney, liver, heart, lung, spleen, and rectum. Congo-red stain was used to identify amyloid deposits and these were characterised further using an indirect immunoperoxidase technique with antibodies to beta 2-M, prealbumin, serum amyloid A protein, and kappa and lambda light chains. All patients with arthropathy had large deposits of beta 2-M amyloid in the articular tissues. In contrast to this, systemic amyloid deposits were only found in four patients and were small and mainly confined to vessel walls. The four patients without joint symptoms had no evidence of systemic or articular amyloidosis. In addition, subcutaneous fat aspirations were carried out in 13 patients with dialysis arthropathy and 12 without arthropathy. Amyloid deposits were only found in two patients with arthropathy. Our results show that dialysis-associated amyloidosis has a predilection for deposition in articular tissues, and that systemic deposits are infrequent, small, and mainly confined to vessel walls. The discrepancy between our post-mortem series and case reports describing large systemic deposits may be due to differences in patient susceptibility.

Clearance of beta-2-microglobulin using continuous ambulatory peritoneal dialysis.

In the 9 continuous ambulatory peritoneal dialysis (CAPD) patients studied, the mean clearance of beta 2-microglobulin was significantly higher using hypertonic as opposed to isotonic exchanges (1 ml/min and 0.75 ml/min, respectively). Clearance of beta 2-microglobulin correlated with the clearance of albumin. The daily mass transfer of beta 2-microglobulin ranged from 19 to 62 mg. Although all the daily production of beta 2-microglobulin is not eliminated in patients on CAPD their serum beta 2-microglobulin levels would be expected to be lower than in patients on haemodialysis. Long-term prospective studies are needed to determine whether lower serum beta 2-microglobulin levels lead to a lower incidence of dialysis amyloid.