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Many patients on haemodialysis (HD) therapy suffer from a dry mouth and xerostomia. This can be relieved by mechanical and gustatory stimulation or palliative care. The aim of this crossover study was to investigate the effect and preferences of a sugar-free chewing gum (Freedent White) and a xanthan gum-based artificial saliva (Xialine) in the management of xerostomia in chronic HD patients. Sixty-five HD patients participated in a 6-week crossover trial. The artificial saliva was rated significantly lower than the chewing gum for effectiveness, taste and a global assessment. No preference differences were found for gender and age, although older subjects rated the artificial saliva with a higher mark. Thirty-nine subjects (60%) preferred chewing gum, 15% (n=10) preferred the artificial saliva. Therefore, both chewing gum and artificial saliva could play an important role in the palliative care of xerostomia in HD patients. [ABSTRACT FROM AUTHOR]

Background: Glucose and glucose degradation products (GDPs) in peritoneal dialysis fluids (PDFs) are both thought to mediate progressive peritoneal worsening., Methods: In a multicenter, prospective, randomized crossover study, incident continuous ambulatory peritoneal dialysis patients were treated either with conventional lactate-buffered PDF (sPD regimen) or with a regimen low in glucose and GDPs: Nutrineal×1, Extraneal×1, and Physioneal×2 (NEPP regimen; all solutions: Baxter Healthcare, Utrecht, The Netherlands). After 6 months, patients were switched to the alternative regimen for another 6 months. After 6 weeks of run-in, before the switch, and at the end of the study, 4-hour peritoneal equilibration tests were performed, and overnight effluents were analyzed for cells and biomarkers. Differences between the regimens were assessed by multivariate analysis corrected for time and regimen sequence., Results: The 45 patients who completed the study were equally distributed over both groups. During NEPP treatment, D(4)/D(0) glucose was lower (p < 0.01) and D/P creatinine was higher (p = 0.04). In NEPP overnight effluent, mesothelial cells (p < 0.0001), cancer antigen 125 (p < 0.0001), hyaluronan (p < 0.0001), leukocytes (p < 0.001), interleukins 6 (p = 0.001) and 8 (p = 0.0001), and vascular endothelial growth factor (VEGF, p < 0.0001) were increased by a factor of 2-3 compared with levels in sPD effluent. The NEPP regimen was associated with higher transport parameters, but that association disappeared after the addition of VEGF to the model. The association between NEPP and higher effluent levels of VEGF could not be attributed to glucose and GDP loads., Conclusions: Study results indicate preservation of the mesothelium and increased peritoneal activation during NEPP treatment. Whether the increase in VEGF reflects an increase in mesothelial cell mass or whether it points to another, undesirable mechanism cannot be determined from the present study. Longitudinal studies are needed to finally evaluate the usefulness of the NEPP regimen for further clinical use.

Background: Standard peritoneal dialysis (PD) solutions contain high levels of glucose and glucose degradation products (GDPs), both contributing to the formation of advanced glycation end products (AGEs). We studied the contribution to plasma GDP and AGE levels of 2 PD regimens that differ in glucose and GDP loads: high load [standard PD (sPD) using 4 glucose-lactate exchanges] and low load [1 amino acid exchange, 1 icodextrin exchange, and 2 glucose-bicarbonate/lactate exchanges ("NEPP")]., Methods: In a prospective crossover study (2 periods of 24 weeks), new continuous ambulatory PD patients were randomized to NEPP-sPD (n = 23) or to sPD-NEPP (n = 27)., Results: After the start of PD, absolute increases were observed in plasma levels of 3-deoxyglucosone (3-DG, 220.4 nmol/L, p < 0.0001) and in N(ε)-(carboxymethyl) lysine (CML) in plasma proteins (0.02 μmol/L CML per 1 mol/L lysine, p < 0.0001). During the first 6 weeks, 3-DG tended to increase more with sPD treatment (p = 0.08), and CML, with NEPP treatment (p = 0.002). In both groups, N(ε)-(carboxyethyl)lysine (CEL) in plasma proteins declined significantly with the start of PD. Treatment with NEPP resulted in higher levels of methylglyoxal (MGO) and lower levels of 3-DG and CEL. Pentosidine in the albumin fraction tended to increase less during NEPP treatment., Conclusions: A low glucose and GDP PD regimen (NEPP) resulted in plasma levels of 3-DG and CEL that were lower than those with a glucose-based sPD regimen. Starting PD with NEPP was associated with a steeper increase in CML, and continuing treatment with NEPP resulted in higher MGO levels.

Introduction: Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare recessive disorder of cholesterol metabolism characterized by the absence of high density lipoprotein (HDL) and the triad of corneal opacification, hemolytic anemia and glomerulopathy., Patients: We here report on FLD in three siblings of a kindred of Moroccan descent with HDL deficiency. In all cases (17, 12 and 3 years of age) corneal opacification and proteinuria were observed. In the 17-year-old female proband, anemia with target cells was observed., Results: Homozygosity for a mutation in LCAT resulted in the exchange of cysteine to tyrosine at position 337, disrupting the second disulfide bond in LCAT. LCAT protein and activity were undetectable in the patients' plasma and in media of COS7 cells transfected with an expression vector with mutant LCAT cDNA. Upon treatment with an ACE inhibitor and a thiazide diuretic, proteinuria in the proband decreased from 6g to 2g/24h., Conclusion: This is the first report that FLD can cause nephropathy at a very early age., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates., Methods: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions., Results: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015)., Conclusions: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

Case report of a 62-year-old woman who developed acute renal failure due to nephrocalcinosis, also called acute phosphate nephropathy, after large bowel cleansing in preparation for colonoscopy using oral sodium phosphate solution (Phosphoral, de Witt, Cheshire, UK). Subsequently her renal insufficiency resolved only partially resulting in stage 4 chronic kidney disease. In retrospect multiple risk factors for this condition (hypertension, diuretics, AT-II receptor blocker, female gender, advanced age and volume depleting due to vomiting and nausea) were identified. If these factors had been taken into consideration prior to prescribing this drug, acute and chronic renal failure would have been prevented. Future investigation of potential risk factors and the exact mechanism of this complication is necessary to identify those patients prone to develop this complication. In the meantime prescribing physicians should be made aware of this complication. On the basis of the current state of knowledge the evidence seems to be quite compelling not to prescribe these drugs in patients with one or more associated risk factors. It could even be argued that these drugs should not be prescribed at all.

Aims: To evaluate acute effects of hemodialysis (HD) on the salivary flow rate, pH and biochemical composition before, during and after completion of a dialysis session., Material and Methods: Unstimulated whole saliva (UWS) and chewing-stimulated whole saliva (CH-SWS) were collected in 94 HD patients. Salivary flow rate, pH, concentrations of total protein, albumin, cystatin C, secretory immunoglobulin A (S-IgA) and of sodium, potassium and urea were measured., Results: HD had an acute stimulating effect on the salivary flow rate (UWSbefore = 0.30+/-0.22 ml/min, UWSduring = 0.39+/-0.25 ml/min, p < 0.005). The mean pH of UWS showed a small but significant increase during HD mainly due to an increased watery secretion from the salivary glands. The salivary biochemical constituents changed markedly, but no significant difference in output was found. The electrolyte concentration did not change significantly during dialysis. The level of urea in CH-SWS declined to 40% (Ureabefore = 25.+/-6.4 mmol/l, Ureaduring = 15.3+/-4.5 mmol/1)., Conclusions: This study shows that HD has significant acute effects on both salivary secretion rate and protein concentrations in saliva. We conclude that the observed changes in salivary concentrations and proteins are mainly due to an increased watery secretion from the salivary glands.

Background: Most patients on haemodialysis (HD) have to maintain a fluid-restricted diet to prevent a high interdialytic weight gain (IWG). The prevalence of xerostomia (the feeling of a dry mouth) is higher in HD patients than in controls. Recently, we demonstrated that xerostomia and thirst were positively correlated with IWG in HD patients. Thus, this may play a role as a stimulus for fluid intake between dialysis sessions. The aim of the present study was to investigate the effect of chewing gum or a saliva substitute on xerostomia, thirst and IWG., Methods: This study was a randomized two-treatment crossover design with repeated measures. After the use of chewing gum or saliva substitute for 2 weeks, a wash-out period of 2 weeks was introduced and hereafter the other regimen was carried out. Xerostomia and thirst were assessed by validated questionnaires as xerostomia inventory (XI) and dialysis thirst inventory (DTI), at baseline and after each treatment period, as were IWG and salivary flow rates., Results: Sixty-five HD patients (42 men, 54.6+/-14.1 years; 23 women, 54.7+/-16.3 years) participated in this study. Chewing gum decreased XI from 29.9+/-9.5 to 28.1+/-9.1 (P<0.05). Chewing gum as well as a saliva substitute reduced DTI significantly (P<0.05), but no differences occurred for the average IWG or salivary flow rates., Conclusions: The use of chewing gum and, to a lesser extent, a saliva substitute may alleviate thirst and xerostomia in some HD patients.

Background: The high Levels of glucose, glucose degradation products (GDPs), and lactate buffer present in standard peritoneal dialysis (PD) solutions contribute to peritoneal damage, malnutrition, and dyslipidemia. Therefore, we studied the feasibility of a PD regimen as low as possible in glucose and GDPs., Methods: In a prospective 30-week study, patients new to continuous ambulatory PD (CAPD) were randomized to either a standard PD regimen (SPD; 4 dwells glucose-/lactate-based) or a low glucose-GDP regimen (NEPP; 1 dwell amino acids, 1 dwell icodextrin, and two dwells bicarbonate/lactate-buffered glucose-based solution)., Results: Results obtained during a 30-week study period for 63 new CAPD patients (30 NEPP, 33 SPD) were analyzed. Intraperitoneal glucose load was lower in the NEPP group (111 +/- 76 vs 159 +/- 40 g/day at 30 weeks, p < 0.001). Dialysis efficacy, ultrafiltration, weight, blood pressure, and laboratory results were similar in the groups, whereas, in the NEPP group, cancer antigen 125 in dialysate effluents decreased less but dialysate-to-plasma ratios were slightly higher., Conclusion: Short-term treatment of new CAPD patients with a PD regimen low in glucose and GDPs is feasible. Dialysis efficacy, ultrafiltration, and metabolic consequences are similar to those during a standard glucose-lactate-based regimen, whereas peritoneal transport seems slightly higher and preservation of mesothelial cell mass better during NEPP.

Background: Patients receiving hemodialysis (HD) have to maintain a fluid-restricted diet. Severe thirst can induce noncompliance to this diet, resulting in an increase of interdialytic weight gain (IWG = weight predialysis - postdialysis) associated with poor patient outcomes. Because oral dryness may contribute to experienced thirst, we investigated the possible relation between thirst, salivary flow rate, xerostomia, and IWG., Methods: Unstimulated (UWS) and stimulated (CH-SWS) whole saliva were collected from 94 HD patients (64 men, 54.8 +/- 15.5 years; 30 women, 59.5 +/- 18.7 years). Secretion rates of saliva were determined gravimetrically. Xerostomia was assessed with a validated Xerostomia Inventory (XI), and thirst with a newly developed Dialysis Thirst Inventory (DTI)., Results: Before dialysis, 36.2% of the patients had hyposalivation (UWS < or =0.15 mL/min). The XI scores had a positive relation with IWG (r=.250, P < 0.001). Gender and age differences were observed for thirst, salivary flow rates, and xerostomia. The prevalence and severity of thirst and xerostomia were greater in younger subjects. Patients with urine output did not differ from those without urine output with respect to thirst, xerostomia, and IWG. Correlations were found between thirst (DTI) and both IWG and xerostomia (XI) (r=.329, P < 0.001, respectively; r=.740, P < 0.001). Other correlations were observed between xerostomia and both the salivary flow rate and total number of medications (r=-.252, P < 0.05, respectively; r=.235, P <.05)., Conclusion: In HD patients, xerostomia (XI) and thirst (DTI) are associated with a higher IWG. Our data provide evidence that, in HD patients, xerostomia is related to both salivary flow rate and thirst (DTI).

Dialysis patients show impaired responses to several vaccines. Limited recent data are available on influenza vaccination in these patients. In the 1998-1999 influenza season, 44 dialysis patients received a standard trivalent vaccination followed by a booster two months later. The serum antibody responses in these patients were compared with those found in healthy subjects. A fourfold rise in serum hemagglutination inhibition titre was achieved in 23-58% of all patients. Protective titres were reached in 53-93% of the patients. Since protective antibody titers can be induced, it is recommended to vaccinate dialysis patients annually against influenza.

Standard glucose-based peritoneal dialysis (PD) solutions have unfavorable effects on the peritoneum and contribute to metabolic abnormalities. A PD regimen in which solutions with an alternative osmotic agent (icodextrin, amino acids) and solutions with a bicarbonate/lactate buffer are combined may reduce those effects. In a prospective crossover study, we randomized new continuous ambulatory peritoneal dialysis (CAPD) patients to one of two groups. One group used 4 exchanges of standard PD (SPD) solution (Dianeal: Baxter Healthcare BV, Utrecht, Netherlands) daily. The second group used 1 exchange of Nutrineal (Baxter Healthcare BV), 1 exchange of Extraneal (Baxter Healthcare BV), and 2 exchanges of Physioneal (Baxter Healthcare BV) daily (NEPP). After 30 weeks of treatment, each group switched over to the other regimen for 24 weeks. Statistical analysis used analysis of variance (ANOVA) for repeated measurements. Of the 74 patients enrolled into the study, 50 completed the full study period (24 NEPP-SPD, 26 SPD-NEPP). With regard to daily ultrafiltration and dialysis efficacy (Kt/V), the NEPP regimen was as efficacious as the standard regimen. The NEPP regimen was found to be safe: body weight, blood pressure, decline in urine volume, residual creatinine clearance, and laboratory measurements did not differ statistically significantly from those measured in the standard regimen. The NEPP regimen was well tolerated and was not accompanied by serious side effects. During the NEPP regimen, bicarbonate was found to be significantly higher in both groups. The NEPP regimen is a feasible treatment schedule for patients starting CAPD.

Intrahepatic cholestasis of pregnancy (ICP) is a rare disease occurring mainly during the last trimester of pregnancy. Pruritus, often accompanied by excoriation of the skin but without other skin lesions, and elevated concentrations of bile acids are characteristic for this disorder. We present a 30-year-old woman with pruritus, elevated bile acids, ASAT and ALAT in the 22nd week of pregnancy. Treatment with ursodeoxycholic acid resulted in complete disappearance of the pruritus and normalisation of the bile acids, ASAT and ALAT. A healthy child was born at term. In the differential diagnosis of liver function abnormalities during pregnancy, ICP should be included. ICP responds very well to treatment with ursodeoxycholic acid, with no detrimental effects for mother and child.

The efficacy and safety of oral pamidronate was examined in a double-blind, placebo-controlled trial in women and men with established osteoporosis. Seventy-eight postmenopausal women and 23 men with at least one prevalent vertebral fracture were randomized separately to 150 mg/day of pamidronate or placebo for 3 years followed by 150 mg/day of pamidronate for an additional 2 years. In addition, all patients received 400 U/day of cholecalciferol and 500 mg/day of elemental calcium. Pamidronate increased significantly bone mineral density of the lumbar spine (LS-BMD) and of the femoral neck (FN-BMD). The total increase in BMD of the spine after 5 years of treatment was 14.3%. Lateral spine radiographs were obtained at baseline and after 3 years of treatment. Fractures of previously normal vertebrae occurred in 15 of 45 patients treated with placebo (33.3%) and in 5 of 46 patients treated with pamidronate (11%). The relative risk was 0.33 (95% CI, 0.14-0.77). Treatment was well tolerated and there was no difference in gastrointestinal toxicity between pamidronate and placebo-treated patients. One hundred fifty milligrams daily of pamidronate is an effective and safe treatment of women and men with established osteoporosis.

The clinical course of a pregnant patient, who presented with progressive dyspnea and heart failure is described. Despite intensive care and resuscitative efforts to mother and child, both expired. The autopsy revealed giant cell myocarditis in the mother. Giant cell myocarditis can affect pregnant patients and should therefore be considered in the differential diagnosis of progressive dyspnea.

In two pregnant women aged 39 and 35, who presented with fever and diarrhoea, Campylobacter was cultured from a blood sample. They were treated with antibiotics. One had a healthy neonate, in the other intrauterine foetal death had occurred. Campylobacter species have increasingly been recognized as possible causes of septic abortion, premature labour and neonatal sepsis. Early recognition and treatment of maternal Campylobacter infection may reduce the risk of serious foetal or neonatal complications.

In 1981 an active programme was started in our centre for living-related kidney donation (LRD). The structure of this LRD programme is described in this paper. Retrospectively the results of this LRD programme were studied. Between 1981 and 1988 139 potential living donors were evaluated. Of all potential donors 47 (34%) actually donated a kidney, including 24 HLA non-identical combinations. Follow-up was obtained until 1990. An acceptable incidence of morbidity and mortality for donors and recipients was observed. A high number of potential donors was excluded during the selection procedure (66%). They were often refused for medical reasons (29%), with a high incidence of renal dysfunction (16%). No long-term adverse effects of nephrectomy regarding decreased renal function, hypertension, or proteinuria were seen. Of all actual donors 23% experienced minor complications after donation. Living-related kidney transplants showed better graft function than cadaveric grafts.

Objective: To determine the quality of care in an intensive care unit., Design: Prospective investigation for one year. Comparison with results from the literature., Setting: Surgical intensive care unit of a community hospital., Patients: Measurement of the APACHE-II-score was performed on days 1, 3 and 7 in all surgical intensive care unit patients admitted during a one-year period. The predicted mortality from the literature was compared with the actual mortality in our hospital., Results: A total of 301 patients were admitted to the intensive care unit. Overall mortality was 9%. All the patients with an APACHE II score above 25 on admission died. The actual mortality was comparable with the predicted mortality from the literature., Conclusion: The APACHE II score can be used to determine the quality of care in an intensive care unit. Early prediction of a bad prognosis makes transportation to a more specialized hospital possible, before irreversible organ damage develops.

Parathyroid subtraction scintigraphy has been performed in 108 patients. In 41 cases scintigraphic findings are correlated with surgical and histologic results. Comparison of sequential data acquisition and dual channel acquisition has been made. As the results of these two protocols are comparable, we prefer the dual channel acquisition because of the smaller chance of introducing subtraction artefacts caused by patient movement.

In a prospective study of 38 patients who presented with hematuria of renal origin, 15 patients were found to have primary IgA nephropathy and 23 had other renal disorders. Sera and renal biopsy specimens of these patients were studied for the presence of macromolecular IgA1 and IgA2 using monoclonal antibodies, and the presence of J-chain as demonstrated either by immunofluorescence or its capacity to bind free secretory component. Circulating macromolecular IgA was found exclusively in the sera of patients (80%) with primary IgA nephropathy. In these sera the polymer/monomer ratio for IgA1 (0.64 +/- 0.13) was significantly higher than for normal human serum (0.39 +/- 0.01) (P less than 0.001), while no differences were found for IgA2. The polymeric IgA1 was isolated from serum by gel chromatography and was shown to have the capacity to bind free secretory component. Direct two-color immunofluorescence studies revealed the presence of only IgA1 in the mesangial deposits and also its capacity to bind free secretory component. We conclude (1) that demonstration of circulating macromolecular IgA in patients with renal hematuria is of diagnostic value and (2) that antigenetic similarities between the circulating and the mesangial macromolecular IgA suggest that dimeric IgA1 is deposited in the mesangium of patients with primary IgA nephropathy.

Two patients, who had had pulmonary sarcoidosis, developed renal failure due to sarcoid granulomatous interstitial nephritis after their original pulmonary symptoms had subsided. Treatment with prednisone resulted in almost complete recovery of renal function. Lysozyme and angiotensin-converting enzyme levels and gallium scintigraphy can be of diagnostic value.

Alcoholic liver disease (ALD) is characterized by elevated serum IgA concentrations, the presence of circulating immune complexes containing IgA, and IgA deposits along sinusoids in the liver. When combined with the presupposed IgA-clearance function of the liver, a causal association between IgA abnormalities and the liver disease in ALD can be suggested. This prompted us to study the presence and concentration of circulating IgA-containing immune complexes (IgA-CIC) in 41 patients with ALD and 41 patients with other nonalcoholic liver diseases having comparable serum IgA levels. We searched for relationships among IgA-CIC and history of alcohol abuse, liver histopathology, and IgA deposits in the liver. Using an anti-IgA inhibition binding assay, 56% of the patients exhibited IgA-CIC in polyethylene glycol precipitate of serum and 38% showed IgA-CIC in whole serum. The prevalence and concentration of IgA-CIC was lowest in cases with nonspecific changes or steatosis in the liver biopsy and highest in cases with hepatitis or cirrhosis (P less than 0.01). The occurrence of IgA-CIC was not related to a history of alcohol abuse or to the presence of IgA deposits along hepatic sinusoids (which occurred in 78% of ALD and 20% of non-ALD cases). A skin biopsy was available from 34 patients (19 with ALD and 15 with non-ALD). In 68% of these biopsies, IgA deposits were observed in superficial blood capillaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic vasculitis is a well-known complication of rheumatoid arthritis (RA). Rapidly progressive glomerulonephritis is commonly associated with vasculitis syndromes but rarely found in RA. This report describes two RA patients with complicating systemic vasculitis who developed rapidly progressive glomerulonephritis with glomerular crescent formation. One recovered after treatment with corticosteroids and cytostatic drugs and the other died of severe systemic vasculitis despite similar therapy.

Macromolecular IgA is found with a relatively high frequency in the sera of patients with IgA nephropathy (IgAN). This macromolecular IgA consists of polymeric IgA, IgA-containing immune complexes, or both. The presence of polymeric IgA antibodies reflects a recent IgA response. Vaccination data in patients with IgAN suggest that these patients respond more vigorously with their mucosal immune system than do controls. The association of exacerbations with upper respiratory tract infections suggests that the immunogenic stimuli probably are of microbial origin and are presented to mucosal surfaces. Analysis by sucrose density ultracentrifugation has shown that the macromolecular IgA may contain IgG, IgA rheumatoid factor, and C3. The search for the antigen or antigens specifically responsible for IgAN has been unsuccessful. Although IgG and IgA rheumatoid factor may contribute, they do not account for the pathogenesis of the disease in all patients. Alternative mechanisms have to be assumed for patients who do not have detectable levels of IgA-containing immune complexes. They could have polymeric IgA or IgA-containing immune complexes intermittently, as has been shown in children with relapsing IgAN. The binding of circulating IgA antibodies to antigens present in the mesangium can lead to the local formation of deposits in the absence of circulating IgA complexes.

The antiplatelet effect of antilymphocyte globulin (ALG) was studied during 49 courses of therapy of 4-5 d given to 43 patients with severe aplastic anaemia. Concomitant corticosteroid therapy was usually given in moderate ( MDC ) dosages from 10 to 30 mg daily (40 courses); in nine courses the ALG infusions were combined with high dose (20 mg/kg) methylprednisolone (HDC). Clinical side effects were mainly seen during the first ALG infusion. In all MDC -treated patients a decrease of the peripheral-blood leucocyte count to 20-30% of the pretreatment level during the first ALG infusion was associated with a severely shortened platelet survival. During subsequent infusions, which were tolerated much better, the survival of transfused platelets increased considerably. In the HDC-treated patients platelet survival was only slightly shortened on the first day of therapy, but the decrease of the leucocyte count was also less in these patients. Diffuse intravascular coagulation, circulating immune complexes and complement activation were excluded as major causes of the shortened platelet survival. Although ALG reacted with platelets in vitro and in vivo (as detected with indirect immunofluorescence), bystander destruction was likely during the first ALG infusion when massive leucocyte destruction occurred.

The frequency of monoclonal gammapathies (MG) and their possible origin were investigated in renal graft recipients undergoing immunosuppressive treatment. In a cross-sectional study, homogeneous immunoglobulins were found in 30% of the patients investigated. This incidence was 10-times higher than that in a control group of patients with chronic renal failure on dialysis treatment. The increase in the frequency of homogeneous immunoglobulins in the renal transplant recipients was related to the age of the patients but not to the duration of the immunosuppressive treatment. A longitudinal study in 55 patients demonstrated that most of the MG reflected transient B-cell monoclonal proliferations, probably due to an immunodeficiency; however, the incidence of benign and malignant B-cell neoplasias seemed also to be unusually high. These findings indicate that the immunosuppressive treatment enhances and accelerates an immunodeficiency which develops spontaneously with aging of the immune system; it also may contribute to the development of other age-related, both benign and malignant monoclonal B-cell proliferative disorders.

Twelve of 60 consecutive adult recipients of cadaver kidney transplants had increased polyethyleneglycol (PEG) precipitable IgM immune complex-like material in their circulation in the first 4 months after transplantation. All 10 recipients with primary CMV and two of four with secondary CMV infections had significant elevations in PEG precipitable IgM that coincided with rises in their CMV antibody titres. Ultracentrifuge analysis demonstrated two peaks of PEG precipitable material with sedimentation rates of about 20S and 40S. Total IgM immunoglobulin levels also were increased in transplant recipients with CMV infections, but this was less specific and occurred in patients without CMV infections. The Clq binding assay, which is more sensitive for IgG than IgM containing complexes, was positive in only three of 10 patients with primary CMV and none of four with secondary CMV. Granular deposits of IgM, but not IgG, were detected in the glomeruli of six of seven transplants biopsied during CMV infection. The PEG-IgM assay was not influenced by rejection or prednisone therapy. Thus, transplant patients, who develop primary CMV infections, produce elevated levels of circulating IgM and IgM immune complex-like material. These findings may help to differentiate CMV infection from transplant rejection as well as to increase our understanding of the special pathogenic properties of CMV in transplant recipients.

Circulating immune complexes were determined with the 125I-Clq binding assay and the conglutinin binding assay in a prospective, longitudinal study of 40 patients with infective endocarditis, 34 patients with endocardial defects and nonseptic fever and 25 patients with septicemia without endocarditis. Fourteen patients with uncomplicated valvular lesions constituted a control group. Upon admission, 63 percent of the patients with infective endocarditis had a positive 125I-Clq binding assay versus 9, 12 and 7 percent, respectively, of the other three groups (p less than 0.001). The incidence of positive conglutinin binding assays became significantly higher during the course of infective endocarditis (53 percent) than during the course of nonseptic fever (21 percent), but, upon admission, this difference was not significant. The high incidence of Clq-binding immune complexes among patients with infective endocarditis could be attributed mainly to those patients with the characteristic features of subacute endocarditis. The incidence of circulating immune complexes in acute endocarditis was low and did not contribute to making the clinically important distinction from septicemia without endocarditis. A rise in the 125I-Clq binding assay levels during the course of infective endocarditis correlated significantly (p less than 0.01) with failure of antibiotic treatment. With the 125I-Clq binding assay, significantly higher levels were found in patients with signs of renal involvement of cutaneous vasculitis than in patients without these extracardiac manifestations of endocarditis. These results show that the determination of circulating immune complexes has clinical implications for both the diagnosis and the management of infective endocarditis and that circulating immune complexes are probably involved in the development of glomerulonephritis and vasculitis.

The relation between renal histologic features and the presence of circulating immune complexes was studied in 50 patients with hematuria. Primary IgA nephropathy was found in 25 patients, and various other forms of glomerulopathy were seen in the remaining 25 patients. Circulating immune complexes were detected with the 125I-C1q-binding assay, the conglutinin-binding assay, and the anti-IgA inhibition binding assay, the latter detecting specifically IgA-containing immune complex-like material. The 125I-C1q-binding assay gave negative findings for all patients except one. With the conglutinin-binding assay, immune complexes were found in a similar frequency for patients with and without IgA nephropathy. However, the anti-IgA inhibition binding assay gave positive results only in patients with primary IgA nephropathy (68 percent) and in none of the other patients. Sucrose density ultracentrifugation, as well as experiments in which the anti-IgA inhibition binding assay was performed with and without pretreatment of serum with polyethylene glycol, showed the presumed IgA immune complexes to have intermediate sedimentation coefficients (11 to 21S). The presence and level of this macromolecular IgA in the circulation correlated significantly (p less than 0.001) with the presence of hematuria in patients who had this clinical manifestation intermittently. Furthermore, a significant correlation (r = 0.69, p less than 0.0001) was found between the degree of hematuria and the degree of positive findings of the anti-IgA inhibition binding assay. This study shows that in patients presenting with hematuria, a positive finding on the anti-IgA inhibition binding assay is restricted to patients with primary IgA nephropathy and therefore could be of diagnostic value.

Using an in-vitro test, the presence of formaldehyde-specific IgE antibodies was investigated in sera from four groups of individuals exposed to formaldehyde by different routes and concentrations. Group (A) 28 subjects living or working in rooms or places where formaldehyde-containing construction materials were used; (B) 18 subjects occupationally exposed to relatively high concentrations of formaldehyde; (C) 12 paramedic employees working in a renal dialysis unit where formaldehyde-sterilized dialysers were being used; and (D) 28 subjects undergoing haemodialysis with these formaldehyde-sterilized dialysers. Formaldehyde-specific IgE antibodies could be detected in only one of the 86 serum samples. This particular sample was from a worker occupationally exposed to formaldehyde (group (B], but who did not show any work-related symptoms. In two pools of control sera from unexposed subjects no specific IgE antibodies to formaldehyde were detected. It is concluded that exposure to formaldehyde, even in relatively high concentrations, rarely evokes the production of specific IgE antibodies. The presence of these specific antibodies is not necessarily attended by allergic symptoms. On the other hand, the symptoms supposed to be related to formaldehyde exposure and reported in this study by 24 out of 28 subjects in group (A), and some of the subjects in groups (B) and (C), cannot be attributed to an IgE-mediated sensitization to formaldehyde.

Serial serum samples from 33 patients with systemic lupus erythematosus were tested for CH50, C3, C4, and circulating immune complexes. Circulating immune complexes were determined by 5 different assays. Disease activity was determined by a scoring system we devised. On an interpatient analysis, overall disease activity correlated significantly with levels of CH50, C3, and a positive result on C1q binding assay. However, with the exception of depressed C3 levels, the sensitivity, specificity, and predictive values of all the serologic tests were low. An intrapatient analysis revealed a patient-specific activity parameter in 11 of the 33 patients. We conclude that these serologic tests are not reliable in assessing disease activity in patients with systemic lupus erythematosus, although a small subgroup of patients will exhibit a patient-specific activity parameter.

An immune complex assay using radiolabelled immunospecific antibodies against human IgG and polyethylene glycol precipitation (IgG-PEG assay) is described. The material reactive in this assay was evaluated using aggregated immunoglobulins, immune complexes prepared in vitro, sera of patients with a variety of disorders and normal human serum. Sucrose density gradient ultracentrifugation showed that only large-sized immune complexes (greater than 25 S) were detected. Comparison of the results of the IgG-PEG assay with those of the C1q binding assay showed a highly significant positive correlation (p less than 0.001). It was found that rheumatoid factors do not influence the results of the IgG-PEG assay. The method described in this study detects specifically immune complexes containing IgG and might be extended to the detection of other constituents of circulating immune complexes.

Four immune complex assays (PEG assays) are described; they are based on the binding of radio-labelled immunospecific antibodies to immune complexes containing IgG, IgA, C3 or C4, and subsequent precipitation with polyethylene glycol. Comparison of the results of the IgA-PEG assay with those of an existing immune complex assay (alpha-IgA-InhBA) showed that the former detects only large-sized (greater than 25 S) material. This was also demonstrated by sucrose density gradient ultracentrifugation of immune complexes in patients' sera as well as in preparations of aggregates containing IgA, C3 or C4. By using aggregates of mixed composition (IgG, IgA, C3 and C4) it was shown that each constituent could be detected by one of the 4 assays. Immune complexes containing the various constituents could also be detected in sera of patients with a variety of disorders. Further studies are needed to establish whether these constituents occur within the same complex or within different complexes.

To evaluate the role of some immunological phenomena involved in the pathogenesis of preeclamptic toxaemia, we studied the humoral immune reactivity in patients with preeclamptic toxaemia during the third trimester of pregnancy, and three days and six weeks after delivery. The results were compared with those of patients with intrauterine growth retardation and with uneventful pregnancy. During the third trimester, patients with complicated preeclamptic toxaemia had significantly lower IgG, CH50, C4 and C3 levels than normal pregnants. Post-partum levels of IgM were significantly higher than in all other groups of patients. Circulating immune complexes were not detectable by a C1q binding assay in patients and controls. However, with a conglutinin binding assay and a granulocyte phagocytosis test complexes were demonstrable in patients with complicated preeclampsia (incidence 44% and 33%, respectively). In addition, 66% of these patients showed deposits of immunoglobulins and complement components in superficial blood vessels of the skin biopsy, suggestive of the presence of tissue deposits of immune complexes. This was found in about 30% of the other patient groups and in none of control pregnants. Allo-antibodies to lymphocytes were present in 63% of complicated preeclamptic toxaemia patients and 22% of normal pregnants. Our data show several changes in humoral immune reactivity in preeclamptic toxaemia which may contribute to the pathogenesis of this disorder.

The formation of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) after single intravenous injections of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) was examined in four patients with chronic renal failure on regular haemodialysis. Following 1-3 micrograms 1 alpha-OHD3, administered at weekly intervals, 1,25-(OH)2D3 appeared in the circulation within 1 h, and peak concentrations were reached between 2 h and 5 h. By 8 h serum 1,25-(OH)2D3 concentrations had started declining and by 44 h they had returned to baseline after 1 microgram 1 alpha-OHD3, but they were still above basal after 2 and 3 micrograms by an average of 30 pmol/l. One week after injections, concentrations were back to basal in all patients studied. The serum 1,25-(OH)2D3 dose response to injected 1 alpha-OHD3 was linear, indicating ample capacity of the liver 25-hydroxylase to further hydroxylate 1 alpha-OHD3. However, examination of the individual responses revealed lower increments in serum 1,25-(OH)2D3 concentrations in the patients with the highest basal serum 25-hydroxyvitamin D concentrations. Intravenous 1 alpha-OHD3 may be useful in the further study of the interactions between 1,25-(OH)2D3, calcium and PTH in chronic renal failure, as well as of the hepatic metabolism of vitamin D.

In a group of 14 patients with chronic renal failure and secondary hyperparathyroidism, subtraction scintigraphy with 201Tl and 99mTc for parathyroid localisation was performed prior to subtotal parathyroidectomy. Fourteen of 38 (37%) enlarged hyperplastic glands found at first operation corresponded with the hot spots seen on the preoperative scans. Four of five (80%) found at a second operation had also been detected this way preoperatively. Postoperative scans were performed in nine patients. All hot foci seen on the preoperative scans had disappeared. In two patients new hot spots emerged correlating with known residual parathyroid tissue, and also in one patient with recurrent secondary hyperparathyroidism. We conclude that this diagnostic method is of limited value prior to the first neck exploration in secondary hyperparathyroidism of chronic renal failure. However it might be a useful method in the evaluation of patients with signs of persistent or recurrent hyperparathyroidism.

Serum and synovial fluid (SF) from 68 patients with rheumatoid arthritis (RA) were studied for the presence of immune complexes (IC) and the results correlated with extraarticular features and/or disease activity. IC were measured by the 125I Clq binding assay (ClqBA) and with one detecting IgG, IgA, C3 or C4 in IC. Disease activity correlated significantly with IgG or IgA containing and Clq binding IC. The IgA containing IC were found only in 25% of the patients, including all but one case of rheumatoid vasculitis, but otherwise only in seropositive active RA. C3 and C4 IC did not correlated with disease activity, seropositivity or vasculitis. IC in serum did not correlate with SF levels, but C4 containing IC were more frequent in SF (60%) than in serum (30%). Thus serum IC did not reflect SF levels. Patients with vasculitis showed more IC in the sera than in SF.