Serum and urine monoclonal immunoglobulins in malignant non-Hodgkin's lymphoma

62 consecutive patients with newly diagnosed malignant non-Hodgkin's lymphoma (NHL) were investigated for the presence, type, and amount of serum and urine monoclonal immunoglobulin abnormalities. The overall incidence of monoclonal gammopathy (MG) was 81%. M components of the IgM and IgG classes were found in the serum of 52% of the patients. Their concentration was below 10 g/l in 54% of cases and above 20 g/l in 26% of cases. The highest incidence of serum M components (75%) was seen in plasmacytoid lymphocytic lymphoma (PLL) and the lowest (38%) in follicular center cell lymphoma. A monoclonal free light chain, i.e., Bence Jones protein (BJP), was documented in the urine of 61% of cases with a daily excretion comprised between 0.01 and 9.24 g. The isolated urinary excretion of BJP was a major finding accounting for 36% of all MG found in association with NHL. It occurred in all histopathological subtypes with a frequency ranging from 17% of PLL to 37% of small lymphocytic lymphoma.     

High incidence of monoclonal proteins in the serum and urine of chronic lymphocytic leukemia patients

Chronic lymphocytic leukemia (CLL) is generally considered a nonsecretory B cell immunoproliferative disorder. Conventional electrophoretic and immunoelectrophoretic methods have revealed serum monoclonal proteins in less than 10% of these patients. However, there is increasing experimental evidence from in vitro studies demonstrating that CLL cells may secrete immunoglobulins, particularly free light chains. We examined the serum and urine of 36 consecutive CLL patients for monoclonal proteins using sensitive immunochemical methods (high resolution agarose gel electrophoresis combined with immunofixation). The results obtained were correlated with the Rai stage, quantitative immunoglobulin levels, and lymphocyte membrane immunoglobulin phenotype of the leukemic cells. Twenty-three monoclonal proteins were identified in the serum or urine of 22 patients, an incidence of 61%. Six patients had serum monoclonal proteins, seven had only urinary monoclonal proteins, and nine had monoclonal proteins in serum and urine. In every instance the monoclonal protein was the same light chain type as expressed on the leukemic cells. Our findings suggest that the monoclonal proteins observed in the serum or urine of CLL patients are secretory products of the tumor cells and that their discovery is a function of the sensitivity of the method used for their detection.     

Free immunoglobulin light-chain serum levels in the follow-up of patients with monoclonal gammopathies: correlation with 24-hr urinary light-chain excretion

In patients with light-chain myeloma or primary AL-amyloidosis, 24-hr light-chain excretion in the urine is considered an essential marker of the tumor mass. However, 24-hr urine collection and analysis may be cumbersome and prone to inaccuracy. Recently, a sensitive immunonephelometric assay for immunoglobulin free light chains (FLC) in the serum was developed. We sought to determine whether the serum level of monoclonal FLC could be used as an indicator of urinary excretion and disease evolution. Seven patients with light-chain myeloma and AL-amyloidosis were studied, all of which had a monoclonal FLC that could be detected in the urine using standard methods. In four of these patients, follow-up revealed a remarkable correlation between FLC serum levels and daily urinary excretions. The ratio of serum level to urinary light-chain excretion, although stable in a given patient, was extremely variable between patients. In the three remaining cases featuring hardly measurable amounts of light chain in the urine, the serum FLC assay proved sensitive enough for correlation with clinical events. Thus, immunonephelometric measurement of serum FLCs is a reliable method for the follow-up of patients with light-chain secreting monoclonal gammopathies.     

A long-term observation of development from monoclonal gammopathy of undetermined significance (MGUS) into primary amyloidosis

The term, "monoclonal gammopathy of undetermined significance (MGUS)" is used because it is not known at the time of recognition whether the M-component will remain stable or will develop into multiple myeloma (MM) or related disorders. Recently, we have encountered a case of MGUS in which a diagnosis of primary amyloidosis (PA) was made more than 10 years after the recognition of an M-component in the serum. A 64-year-old man presented in 1979 for evaluation of monoclonal gammopathy. The level of M-component (IgG-lambda) in the serum was 1.6 g/dl. The urinary Bence Jones proteins (BJP) were negative. Bone marrow aspirate contained 9.8% plasma cells. Skeletal surveys were normal. A diagnosis of MGUS was made. In 1982, a trace amount of BJP was detected in the urine. Since 1988, carpal tunnel syndrome, angina pectoris and congestive heart failure developed in succession. In November 1989, the patient was admitted to Kyoto University Hospital for examination. Serum electrophoretic pattern remained unchanged. The excreted amount of urinary BJP was less than 0.3 g/day. Bone marrow aspirate contained 5.4% plasma cells. Histologic studies of bone marrow biopsy specimens revealed amyloid deposition. An echocardiogram was thought to reveal amyloidosis. Significant uptake of Tc-99m (V) DMSA was found in carpal regions, kidneys and heart. A diagnosis of PA was made. It is noteworthy that the development of PA did not accompany an increase in the serum M-component. An early diagnosis of PA as well as MM should be kept in mind in the follow-up study of patients with MGUS.     

Demonstration and identification of monoclonal proteins in the urine of patients with Sj?gren's syndrome.

Fresh sera and concentrated urine from 17 patients with primary Sjögren''s syndrome (SS) were fractionated by high-resolution agarose electrophoresis to investigate the presence of monoclonal immunoglobulins or their components. Homogeneous protein bands were found in the gamma-globulin region in 47% of serum samples and 76% of urine specimens of all patients tested. These monoclonal proteins were detected more often in patients with extraglandular SS (77% in serum, 100% in the urine) than in patients with glandular SS (14% in serum, 43% in the urine). Immunofixation electrophoresis showed that the majority of these monoclonal proteins were free kappa or lambda light chains. Fractionation of unconcentrated parotid salivas from five SS patients failed to reveal the presence of monoclonal light chains or immunoglobulins. The present findings further substantiate our previous observation that a monoclonal process coexists with the polyclonal activation in SS patients.     

Kidney failure in a patient with chronic B-lymphocytic leukaemia (B-CLL) with underlying cast nephropathy. The value of free immunoglobulin light chain identification for early diagnosis of this complication

We describe a case of an untreated female patient monitored over 8 years for chronic B-lymphocytic leukaemia (B-CLL). Over the 8 years, the patient has gradually developed severe kidney failure, even though the criteria for B-CLL treatment had not been fulfilled. Kidney biopsy revealed renal damage due to lamda free light chains cast nephropathy as well as an infiltration of renal parenchyma with B-CLL cells. It was not before this biopsy that the presence of monoclonal immunoglobulins has been investigated. Immunofixation identified free monoclonal lamda light chains in the serum and urine. Their serum concentration, quantified by densitometry, was 2.6 g/l and urine concentration was 0.5 g/l. A specific evaluation of free light chains in the serum revealed an extremely high concentration of free X light chains, over 4500 mg/l, and normal concentration of K free light chains, 10 mg/l. The aim of this report is to emphasise that monoclonal immunoglobulin may be present in B-CLL as well as other lymphoprolipherative diseases and that it may cause damage to organs, similar to multiple myeloma or monoclonal gammopathy of undetermined significance. The described case confirms poor prognostic value of monoclonal immunoglobulin free light chains in patients with B-CLL and usefulness of an evaluation of their presence in patients with B-CLL, particularly if the patients have increased creatinine level. The described case also highlights the need for evaluation of the presence of free light chains in the serum of all patients with unclear cause of renal failure.     

The occurrence of renal involvement in primary Sj?gren's syndrome: a study of 78 patients.

OBJECTIVE:To ascertain the occurrence of renal involvement in patients with primary Sj?gren's syndrome (pSS). METHODS:Urinary total protein excretion from 24 h urine collection, as well as urinary excretion rates of albumin, alpha-1 microglobulin (alpha1m) and IgG from overnight 8 h collections, were determined from 78 pSS patients (75 females, three males). Urine acidification capacity after oral ammonium chloride load was tested in 55 of these patients. RESULTS:Mild proteinuria (0.15-0.42 g/24 h) was observed in 34 patients (44%). Increased urinary excretion rates of albumin (>/=20 microgram/min), alpha1m (>/=7.0 microgram/min) or IgG (>/=5.0 microgram/min) were detected in nine (12%), nine (12%) and 11 patients (14%), respectively. Latent or overt distal renal tubular acidosis (dRTA) was observed in 18 out of 55 patients with pSS (33%). These patients had a longer duration of the disease (10+/-4 vs 8+/-4 yr; P相似文献   

Monoclonal gammopathy of undetermined significance. Natural history in 241 cases

Two hundred forty-one patients with a monoclonal protein in the serum but initially no evidence of multiple myeloma, macroglobulinemia, amyloidosis or lymphoma were followed up for more than five years. At the conclusion of the studies the patients were classified as follows: Group 1, patients without significant increase in monoclonal protein, 57 per cent; group 2, patients with more than 50 per cent increase in monoclonal serum protein or development of monoclonal urine protein, 9 per cent; group 3, patients who died without five-year serum studies, 23 per cent; and group 4, patients in whom myeloma, macroglobulinemia or amyloidosis developed, 11 per cent. Initially, the hemoglobin level, size of serum monoclonal protein peak, number of plasma cells in the bone marrow and levels of normal immunoglobulins were not significantly different among the four groups. The median interval from recognition of the monoclonal protein to diagnosis of multiple myeloma was 64 months, of macroglobulinemia 103 months and of amyloidosis 92 months. A significant increase of the monoclonal protein or development of myeloma, macroglobulinemia or amyloidosis occurred in 18 per cent of the patients with monoclonal immunoglobulin G(IgG), in 28 per cent with immunoglobulin A (IgA) and in 25 per cent with immunoglobulin M (IgM). Retrospective analysis of age, sex, presence of organomegaly, hemoglobin level, size and type of serum monoclonal protein peak, presence of small amounts monoclonal light chain in the urine, serum albumin level, levels of uninvolved immunoglobulins, IgG subclass and level of plasma cells in the bone marrow did not show how to distinguish initially between stable benign disease and progressive disease. Therefore, periodic reexamination of patients with monoclonal gammopathy is essential.     

Selective urinary excretion of phosphatidyl ethanolamine in patients with chronic glomerular diseases

Urinary phospholipids and lipoproteins in chronic glomerular diseases were analyzed. The subjects used were 26 patients consisting of 14 with chronic glomerulonephritis and 12 with nephrotic syndrome. Nine healthy normals served as controls. Phospholipids were isolated by one-dimensional thin-layer chromatography (TLC) using an internal standard for quantification and partially by two-dimensional TLC and, furthermore, quantified by two different methods to ascertain the kinds of phospholipids. Urinary lipoproteins were isolated by density gradient ultracentrifugation and analyzed by electrophoresis. The urinary excretion of phosphatidyl ethanolamine (PE) was recognized exclusively in the patient group and that of phosphatidyl serine (PS) in most cases with nephrotic syndrome. The daily urinary PE excretion rate was closely correlated to the urinary albumin excretion rate. However, phosphatidyl choline (PC) and sphingomyelin (SPH), which are main phospholipids in serum and red blood cell membranes, in most cases were hardly detected in urine. These observations were confirmed by two-dimensional TLC using valuable spot tests for identification of phospholipids and also by the two different quantification methods. In density gradient ultracentrifugation, urinary lipoproteins did not form such peaks as seen in the profiles of serum lipoproteins. The presence of urinary lipoproteins in two nephrotic patients has been shown, but although the method used was not very sensitive, it was suggested that lipoproteins were hardly excreted into urine as the lipoprotein deficient fraction (LPDF) (d > 1.21 g/ml), in which albumin is predominant. PE was found mainly in LPDF of urine, although the amount of PE in urinary lipoproteins was very limited. These data gave a basis for a postulate that the urinary excretion of PE may not be related to the excretion of lipoproteins but to LPDF albumins. From the practical absence of PC and SPH in urine, it was further postulated that choline-containing phospholipids (PC, SPH) may not have been excreted in sufficient quantities in these patients.     

Serum levels and urinary excretion of soluble receptors for tumor necrosis factor (sTNF R) in patients with primary glomerulonephritis

Tumor necrosis factor alpha (TNF-alpha) is a pro-inflammatory cytokine and has multiple physiological function. Its binding to specific receptors produced the reactions of TNF. In sera and urine of healthy persons and diseased patients two soluble types of TNF receptors--p55--sTNF I and p 75--sTNF RII have been detected. They can protect cells against excessive cytotoxic activity TNF-alpha in vitro and in vivo. The aim of the work was to investigate the prognostic significance and role of sTNF R in various types of glomerular diseases. We studied 49 patients with primary glomerular diseases (5 minimal change--MC; 4 focal glomerulosclerosis--FS; 4 membranous nephropathy--MN; 12--mesangial proliferative GN--MesPGN; 18 IgA nephropathy--IgAN; and 6 membranoproliferative GR--MPGN) and 10 healthy persons. Renal biopsies were evaluated by light and immunofluorescence microscopy. sTNF RI and sTNF RII concentrations were measured by ELISA (BIOSOURCE International kits). The treatment of patients consisted of 3 to 5 i.v. methylprednisolone pulses (1.0 g per single dose, average total 1.0 g/20 kg given alternate days) followed by oral prednisone 20 to 25 mg/day and six monthly i.v. cyclophosphamide 0.6 g/l m2/month. The study groups showed a significantly higher concentration of sTNF RI and sTNF RII in their sera and urine compared with the control. In patient groups serum Cr showed significant correlations with interstitial volume in renal biopsy, correlation serum Cr with serum sTNF RI, serum sTNF RI with serum sTNF RII and with urinary sTNF RI, serum sTNF RII with urinary sTNF RI and with urinary sTNF RII. The ratio of serum sTNF RI to serum sTNF RII in patients was unchanged compared to the controls but ratio urinary sTNF RI to sTNF RII was higher in all patient groups except patients with MC. In patients with renal sufficiency (Cr < 1.3 mg%) and reduction of proteinuria > 50% after 1 year treatment urinary secretion of sTNF RII was higher before treatment than in patients with protein reduction < 50%. In patients with renal insufficiency and reduction of proteinuria > 50% urinary excretion of sTNF RI was lower than in patients with lower reduction of proteinuria (< 50%) after 1 year treatment. These results suggest that serum sTNF R could be useful as indicator of clinical disease activity but urinary excretion permits prediction of reduction in proteinuria.     

Urinary phospholipase A2 excretion in chronic pancreatic diseases.

This study was performed to investigate the behavior of phospholipase A2 (PLA2) in serum and urine of patients with chronic pancreatic diseases and to ascertain whether any factors influenced the results. In 30 controls, 45 patients with pancreatic cancer, 54 with chronic pancreatitis, and 64 with extrapancreatic diseases, serum and urinary PLA2, pancreatic isoamylase and RNase, and urinary N-acetylglucosaminidase (NAG) were measured. Serum PLA2 levels were higher in patients with chronic pancreatitis than in all the other groups. In our patients, only occasionally was urinary PLA2 elevated, the increase occurring almost exclusively in the presence of an acute inflammatory disease, e.g., relapsed chronic pancreatitis or active inflammatory bowel disease. A correlation was found between serum PLA2 and serum RNase, an indicator of tissue damage, but not between serum PLA2 and pancreatic isoamylase. Urinary PLA2 output was correlated with its renal input and with RNase output. No correlation was found between PLA2 output and pancreatic isoamylase or NAG urinary excretion. In conclusion, (1) the determination of serum PLA2 activity may be an aspecific test of pancreatic disease; (2) PLA2 urinary excretion occasionally increases, especially in the presence of severe phlogosis, which occurs in chronic pancreatitis, in particular during relapse; and (3) irrespective of the tissue origin of urinary PLA2, its increased excretion may be accounted for in part by its increased circulating levels. It is, however, more likely the consequence of a renal tubular dysfunction, which is sometimes found in patients with pancreatic diseases.     

Immunoglobulin abnormalities in malignant non-Hodgkin's lymphoma

The association of monoclonal gammopathy and lymphoma was investigated in 100 consecutive, untreated cases of chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL) of B-cell type, classified according to the criteria of Lukes & Collins (9). The overall incidence of monoclonal immunoglobulins (Ig) was 24%. The highest incidence (57%) was seen in plasmacytoid lymphocytic lymphoma and the lowest (7.9%) in cases of CLL. IgM was the predominant class of monoclonal Ig. It is concluded that the presence of monoclonal gammopathy in NHL reflects the stage of differentiation and maturation of the malignant B-cell clone.     

Myeloma protein kinetics following chemotherapy

The effects of chemotherapy were evaluated in 43 multiple myeloma patients with high monoclonal globulin levels in both serum and urine. In responding patients, Bence Jones protein excretion declined more rapidly and markedly than the serum myeloma protein. Bence Jones protein excretion was reduced by 50% within 2 mo in responders, remained unchanged in nonresponders, and declined with a slow halving time of 2-7 mo in patients with partial disease control. Three patients with clinical resistance to treatment showed atypical protein changes and progressively more Bence Jones protein excretion relative to their serum monoclonal component. Serial measurements of Bence Jones protein excretion provided an early and reliable index of tumor mass change in patients with multiple myeloma.     

Serum level and urinary excretion of RANTES in patients with primary glomerulonephritis

Proteinuria plays a central role in the progression of glomerular disease, and there is growing evidence suggesting that it may determine tubular cell activation with release of proinflammatory chemokines and fibrogenic factors, leading to interstitial inflammatory reaction. Chemokines are proteins that contribute to the migration of leukocytes to sites of tissue injury. C-C chemokine receptor 5 is receptor for the C-C chemokine RANTES, which is expressed in inflammatory kidney diseases. To better understand the role of RANTES in various types of human glomerular diseases, we studied 53 patients with primary glomerular diseases (5 minimal change--MC; 4 focal glomerulosclerosis--FS; 4 membranous nephropathy--MN; 12--mesangial proliferative GN--MesPGN; 18 IgA nephropathy--IgAN; 6 membranoproliferative GN-MPGN, and 4 extracapillary GN-ExGN) and 10 healthy person. Renal biopsies were evaluated by light and immunofluorescence microscopy. RANTES concentrations in serum and urine were measured by ELISA (BIOSOURCE international kits). The treatment of patients consisted of 3 to 5 i.v. methylprednisolone pulses (1.0 g per single dose, average total 1.0 g/20 kg given alternate days) followed by oral prednisone 20 to 25 mg/day and six monthly i.v. cyclophosphamide 0.6 g/l m2/month. The study groups (except FS) showed a significantly higher concentration of RANTES in their sera compared with the control. The increase of urinary excretion for RANTES was 2-fold in patients with MN, and 8-fold in patients with ExGN but in patients with FS a significant decrease in urinary RANTES excretion was found. There was no significant differences in the urinary excretion of RANTES in other groups compared to a control group. In patient groups serum Cr showed significant correlations with interstitial volume in renal biopsy. No significant correlation was found between serum concentration of RANTES and their urinary excretion and other parameters considered (serum creatinine, urinary protein, serum protein concentration, and interstitial volume in renal biopsy). In patients with renal insufficiency (Cr > 1.3 mg%) and reduction of proteinuria > 50% after 1 year of treatment, the serum concentration and urinary secretion of RANTES was higher before treatment than in patients with protein reduction < 50%, and in patients with renal sufficiency. These results showed that patients with glomerular diseases who showed renal insufficiency and reduction of urinary protein after 1 year of immunosuppressive treatment revealed high levels of serum and urinary excretion of RANTES. It was thus suggested that the measurement of serum and urinary excretion of RANTES is useful in evaluating the degree of renal injury in patients with glomerular diseases after immunosuppressive treatment.     

The Physiopathological Significance of Benign Monoclonal Gammopathy: a Study of 64 Cases

Sixty-four patients with monoclonal protein in serum but initially without evidence of multiple myeloma, macroglobulinaemia, amyloidosis or lymphoma, were studied. Fifty patients (78%) were observed for a period exceeding 3 years. Based on the follow-up data the patients were classified into the following four groups: Group 1=patients with transient monoclonal gammopathy: 4.7%; Group 2 = patients without significant increase in monoclonal serum protein: 75%; Group 3 = patients with more than 50% increase in monoclonal serum protein: 14.1%; Group 4=patients in whom multiple myeloma developed: 6.2%. The mean interval from discovery of the serum monoclonal protein to evolution to multiple myeloma was 61 months. Retrospective analysis of age, sex, blood count, bone marrow picture, antigenic type and size of serum monoclonal proteins, presence of small amounts of homogeneous light chain in the urine, serum albumin level, levels of residual immunoglobulins, did not help to distinguish initially the patients in whom the monoclonal gammopathy evolved to multiple myeloma from patients in whom the disease remained benign and stable. The evolution to multiple myeloma had occurred abruptly after long periods of stable condition; and until this progression the follow-up data were similar to the patients with benign disease. The possible physiopathology of occurrence and evolution of benign monoclonal gammopathy is discussed.     

Immunophenotypic diagnosis of clinical and preclinical chronic lymphatic leukemia by using monoclonal antibodies against the cCLLa, a CLL-associated antigen

The clinical usefulness of monoclonal antibodies (MoAbs) against the cCLLa, an antigen restricted to B-chronic lymphatic leukemia (CLL) and its variants, was ascertained in 65 patients with overt CLL and 25 individuals with unexplained mild lymphocytosis. Healthy volunteers (n = 25) and patients with malignant and nonmalignant disorders (n = 58) served as controls. The following observations were made in CLL. (a) Anti-cCLLa MoAbs identified neoplastic CLL cells as judged by the high correlation (r = .985) between monoclonal surface immunoglobulins (Slgs) and cCLLa expression in all patients, and dual-label flow cytometry studies showing cCLLa expression by monoclonal Slg-bearing B- CLL cells but not by normal B lymphocytes. (b) The size of the circulating cCLLa-positive clone paralleled the degree of lymphocytosis (r = .987) and was associated with reciprocal (r = .893) relative T lymphopenia. Ten patients with borderline lymphocytosis exhibited a subset of monoclonal Slg/cCLLa-positive cells ranging from 16% to 45% of the total. These patients were indistinguishable from those with CLL in terms of age, clone lineage, and reciprocal relative T lymphopenia. Two patients have progressed to overt CLL within 19 months, but eight have not (observation time, 18 to 82 months). These data suggest that anti-cCLLa MoAbs are sensitive probes useful to identify and monitor cCLLa clones during their clinical and preclinical phases.     

Renal function in newly diagnosed multiple myeloma — A demographic study of 1353 patients

This study describes the occurrence of renal failure among 1353 newly diagnosed cases of multiple myeloma. Renal function was evaluated by serum creatinine concentration in 1353 cases, 31% of whom had renal failure at the time of diagnosis. In 1206 cases an estimation of creatinine clearance was made. When renal failure was defined by using creatinine clearance estimation, 49% had renal failure at the time of diagnosis. Renal failure was present in 24% of patients with an M component of IgG-, 31% of IgA- and 100% of IgD-type. 52% of patients with light chain disease had renal failure. The frequency of renal failure was similar in lambda-and kappa-light chain disease. Patients with a high excretion of Bence Jones protein in the urine (> 10 g/24 h) had renal failure significantly more often than patients with lower excretion. Renal failure was related to advanced disease; 41% of patients with stage III (Durie-Salmon) disease had renal failure. Renal failure was found in 45% of patients with hypercalcaemia. When estimated creatinine clearance was used as a predictor of renal function, the same trends were found as mentioned above. In addition, the proportion of patients with renal failure was found to increase with advancing age.     

Intestinal Permeability to 99mTc-Diethylenetriaminopentaacetic Acid in Inflammatory Bowel Disease

Intestinal permeability in inflammatory bowel disease and its relation to periods of disease activity has been investigated by measuring the urinary excretion of DTPA labeled with 99mTc. Urine excretion in 10 control subjects was 2.7 +/- 1% of the test dose. Twelve patients with ulcerative colitis excreted 5.08 +/- 1.6% in remission, 10.61 +/- 2% during periods of mild activity, 19.41 +/- 0.9% during moderate activity, and 15.41 +/- 6.3% with severe activity. Sixteen patients with Crohn's disease excreted 5.7 +/- 1.9% in remission, 8.47 +/- 2.8% during mild activity of the disease, and 14.29 +/- 5.8% during moderate activity. No differences were observed between ulcerative colitis and Crohn's disease, or between ileal and colonic forms of Crohn's disease. Excretion in remission was significantly greater than in control subjects and there was a correlation between excretion and disease activity. In serial determinations done in seven patients we found that urine excretion of the test substance correlated with disease activity. We also studied DTPA excretion in 10 cases with gastric or duodenal ulcer (2.28 +/- 1.4%), six cases of acute gastroenteritis (4.87 +/- 3.1%) and nine cases with other intestinal diseases (3.6 +/- 1.1%). In all these cases, DTPA excretion was lower than in inflammatory bowel disease. Our results show that the urinary excretion of DTPA is a simple test that measures accurately the degree of activity of inflammatory bowel disease. The test is useful in Crohn's disease as well as in ulcerative colitis, and detects intestinal permeability abnormalities even in clinical remission. Significantly lower excretions are found in other intestinal diseases. The test may be recommended as a screening test for use in clinical practice.     

Urinary monoclonal free light chains in primary Sj?gren's syndrome: an aid to the diagnosis of malignant lymphoma.

Three patients, two with typical primary Sjögren''s syndrome (SS) and the third with several features of SS, including abnormal sialography and reduced tear secretion, developed B cell non-Hodgkin''s lymphoma (NHL) of parotid or lung, or both. Isoelectric focusing of concentrated urine specimens in agarose, followed by immunofixation, demonstrated the presence in each patient''s urine of monoclonal free light chains of the same class as that shown on the tumour cells. In one patient the level of urinary free light chains was monitored and found to correlate with disease activity. Similar techniques showed no monoclonal light chains in the urine from a further 26 cases of SS with no clinical evidence of lymphoma. The detection of monoclonal urinary free light chains may provide an early diagnostic clue to the development of lymphoma in patients with SS and be a means of tumour monitoring.     

Renal stones in Wilson's disease.

Fifty-four patients with Wilson's disease were studied with regard to renal stones. Seven of the 45 patients (16 per cent) who underwent roentgenographic procedures of the urinary tract had unequivocal evidence of renal stones. In four of the seven patients with Wilson's disease who had renal stones, the stones were discovered at the time or before the diagnosis of Wilson's disease was made. Of the several possible factors that may predispose patients with Wilson's disease to renal stone formation, the renal tubular acidosis pattern of abnormality in acid-base excretion is probably the most significant. In general, patients with renal stones and unexplained neurologic, bony or hepatic abnormalities should be screened for Wilson's disease by slit-lamp examination, determination of serum copper and ceruloplasmin concentrations, and urinary excretion of copper, particularly if they have relatively alkaline urine.