Search

Summary Seventy-five Norwegian patients with ankylosing spondylitis (AS) were studied for class-specific antibody response against synthetic peptide, P81, representing the sequence of plasmid-coded outer membrane protein of Yersinia (YOP1) containing four amino acid homology (TDRK) with HLA-B27 sequence. Ten (16.7%), five (8.3%) and seven (11.2%) of 60 male AS patients showed elevated anti-YOPI P81 antibody of IgA, IgG, and IgM class, respectively, whereas for each isotype only one (4%) of 25 healthy male controls was positive. Differences were not observed between female patients and controls. In all isotypes, antibody-positive patients were more frequently found in patients with active disease. The anti-YOP1 P81 antibody levels of the patients were generally not correlated with the antibody levels against the peptide representing the hypervariable region of HLA-B27 (B27 peptide). However, in one patient the antibody was shown to react with both peptides by cross-inhibition analysis. Overall, it appears that any causal relationship between YOP1 and pathogenesis of AS is not strong. Immunogenicity and cross-reactivity of the YOP1 region encompassing the TDRE sequence particularly at the T cell level require further study.

We report on a patient with peripheral facial nerve palsy and blurred near vision in association with sulphasalazine treatment. The possibility of this being an adverse reaction to sulphasalazine is discussed.

Peripheral neuropathy (PN) is reported to occur in 5-27% of patients with systemic lupus erythematosus (SLE) mostly as a length-dependent sensorimotor axonopathy. Studies over time have not been performed. Design - Longitudinal study.Thirty-three Caucasian SLE patients consented to participate in the study and were subjected to clinical examination, laboratory tests, and nerve conduction velocity (NCV) studies. At the follow-up 7 years later, 7 patients (21%) were dead, 4 refused to participate, and 2 did not want to perform NCV studies. Twenty patients were thus available for longitudinal study.When all SLE patients were considered on a group basis at follow-up, 8 (33%) out of 24 NCV parameters showed significant deterioration despite correction for time, while 16 (67%) were unchanged. Analysis of change from baseline showed that, except for F-responses, several NCV changes were highly dependent (negative regression coefficients) on baseline levels at start of study. No demographic, laboratory, or disease associated quantitative factor was associated with these changes in NCV parameters over time. Nor was a consistent effect on NCV parameters from any qualitative demographic or disease associated factor confirmed by Repeated Measures ANOVA analyses.A modest progressive neuropathic process exists in patients with SLE. Important is also the finding that, over time, the abnormalities of NCV parameters fluctuate in the individual patients, and the impairments are not necessarily irreversible. This study also shows no association to medication, demographic-, or other disease associated factors.

Headaches--especially of migrainous type--have been considered part of the disease spectrum of systemic lupus erythematosus (SLE). We wished to characterize prevalence and types of headaches in SLE and find out if headache is associated with disease, personality traits, or other psychological factors.Fifty-eight consecutive Caucasian patients with SLE were given a clinical examination. We recorded SLE disease activity according to the SLE Disease Activity Index, types of headache according to International Headache Society criteria, and personality traits and emotional status according to Minnesota Multiphasic Personality Inventory-2 and Beck Depression Inventory (BDI).Thirty-eight SLE patients (66%) were headache sufferers; of these, 22 patients (38%) had migraine and 21 (36%) had tension-type headache. Headaches were not associated with disease activity or any other disease associated variable, including tests for antiphospholipid antibodies. Migraine was associated only with a tendency to social isolation and anxiety, while tension-type headache was associated with psychological distress, such as anxiety, somatic complaints, reduced energy, mental tension, social discomfort and withdrawal, and depressive mood according to the BDI. CONCLUSION; Migraine and tension-type headaches occur frequently in patients with SLE. Migraine shows the same clinical presentation as in a non-SLE population, and may not be part of a neuropsychiatric disease spectrum. This also applies to tension-type headache, which in contrast to migraine shows some associations with emotional and personality traits, and could represent components of a chronic pain syndrome.

To examine changes in health status, disease activity, and organ damage after 2 years and to study possible disease variables predicting change in health status, disease activity, and organ damage at followup in systemic lupus erythematosus (SLE). Second, to compare changes in health status in patients with SLE to that of matched patients with rheumatoid arthritis (RA) and matched healthy controls.A 2 year longitudinal observational study, measuring health status (Short-Form 36. visual analog scale for pain and fatigue, modified Health Assessment Questionnaire, patient global assessment of disease activity), disease activity, and organ damage in 87 patients with SLE. Health status measures in SLE were compared to 65 matched RA patients selected from the Oslo RA register and to 77 matched healthy controls from the population register.On a group level the SLE patients showed stable health status measures and disease activity scores 2 years after baseline, but organ damage scores increased significantly. Increase in organ damage was significantly and independently predicted by baseline scores of disease activity and organ damage, health status, and disease activity by the respective baseline scores. Changes in health status measures over 2 years were similar in SLE, RA, and healthy controls.Our 2 year longitudinal observational SLE study showed a stable course of health status and disease activity, whereas organ damage increased. Disease activity and organ damage at baseline predicted the latter. Our results indicate the value of careful monitoring of disease activity over time in SLE and individually tailored treatment guided by the predictors of course and outcome.

To examine health status in systemic lupus erythematosus (SLE), using both generic and arthritis-specific instruments, and compare the health status in patients with SLE to matched patients with rheumatoid arthritis (RA) and matched healthy controls. As well, to study possible correlations between health status measures and demographic and disease variables in the patients with SLE.Patients were recruited from the Oslo county registers of patients with SLE and RA, and the healthy controls from the county population register. Measures of health status (Medical Outcome Survey SF-36, joint pain and fatigue on visual analog scale, Modified Health Assessment Questionnaire) were obtained from 82 SLE and 82 RA patients matched for age, sex, and disease duration, and from 74 age and sex matched healthy controls. Disease activity and organ damage were assessed in the patients with SLE.Patients with SLE were significantly more affected in all dimensions of health status compared to controls, except in the SF-36 category role-emotional. Further, patients with SLE were significantly less affected than patients with RA with regard to physical function and joint pain, but scores were similar in all other dimensions of health status. Scores of health status correlated more strongly to the damage index than to disease activity, indicating that health status measures capture some of the same concept as the damage index, namely the consequence of the disease over time.Our study showed that patients with SLE and RA have a multidimensional involvement of health status compared to healthy controls. The findings call for a biopsychosocial approach in the management of SLE.

As part of our quality assurance programme we designed special questionnaires which addressed expectations concerning medical aspects and service at our out-patient rheumatology clinic, and the degree of satisfaction. These questionnaires were answered by 97 patients, 86 referring general practitioners and five rheumatologists. The principle purpose of the consultation with the specialist, both for patients and referring practitioners, was to obtain or confirm the diagnosis. 76% of the patients and 91% of the general practitioners were satisfied with the medical aspect of the consultation. The dissatisfied patients were mainly those with symptomatic diagnoses (pain syndromes) not explained by objective changes. As for the service, long waiting time before consultation or before receiving the specialist's report was the main reason for dissatisfaction among patients and referring practitioners respectively.

Twenty five patients (12 with systemic lupus erythematosus, 6 with Wegener's granulomatosis, and 7 with miscellaneous rheumatic diseases) who had been on intravenous or oral cyclophosphamide pulse therapy for more than 3 months were evaluated for safety of treatment. Side effects were reported by 20 patients (80%), mainly nausea (17 patients, 68%). Complications were observed in 13 patients (52%), of whom 6 had severe infections (24%). Oral cyclophosphamide given in repeated low dose pulses (5 mg/kg for 3 consecutive days) is better tolerated with regard to nausea than intravenous administration. The use of cyclophosphamide therapy is recommended in patients with disease that does not respond to conventional regimens, although the attending physician should be aware that infections may appear at any time during treatment, and effective prophylaxis against nausea is required.

A population survey of the Sami (Lapp) population of the municipalities Karasjok and Kautokeino in north Norway revealed a prevalence of ankylosing spondylitis (AS) according to the New York criteria of 1.8%. Eleven cases of AS were found, 7 men and 4 women. Only 4 of the 11 observed cases of AS were aware of the diagnosis of AS prior to the survey. Ten of 11 patients with AS possessed HLA-B27 (91%) which is found in 24% of the general Sami population in this area. It was calculated that 6.8% of B27 positive persons had AS.

The article describes two cases of adult Still's disease and reviews the relevant literature. Adult onset Still's disease is characterized by high peaks of fever, arthritis, arthralgia, rash, increased erythrocyte sedimentation rate, leucocytosis, liver dysfunction and negative tests for antinuclear antibodies and rheumatoid factors. Still's disease should be regarded as a possible differential diagnosis in adult patients who present such features.

We systematically evaluated muscular weakness in a series of patients with systemic lupus erythematosus (SLE) using standardized neurological scoring systems, namely Neuropathy Symptom Score for symptoms, and Neurological Disability Score for signs. Symptoms of weakness were statistically associated with clinical and electrophysiological evidence of nerve and muscle disease. Signs of weakness were statistically associated with malaise, disease activity, anemia, age, and raised erythrocyte sedimentation rate. Various disease associated variables influenced symptoms and signs differently. It is important to define a baseline characterizing muscular weakness in SLE before conclusions are drawn regarding its significance and prevalence.

Systemic lupus erythematosus is a disease characterized by multiple autoimmune phenomena, and a broad clinical spectrum. Involvement of the central nervous system is common, and in the majority of patients occurs mainly as an organic brain syndrome or as migraineous headache. Cerebral atrophy as judged by CT scan is common. Cerebral infarction occurs in a minority of patients, mainly those with high disease activity and a high titer of anti-phospholipid antibodies. Systemic lupus erythematosus should be considered as a possible diagnosis in patients with certain central nervous system aberrations, especially young females.

Systemic lupus erythematosus (SLE) gives rise to a variety of autoimmune and clinical phenomena in a multisystem manner. Both the central and peripheral nervous systems are involved as well as skeletal muscle. Based on our work with SLE patients, we describe the different categories of peripheral neuropathy and myopathy. We suggest that the disease be considered as a possible diagnosis, especially when evaluating women with symptoms and signs of neuromuscular abnormalities.

Summary Eight children with chronic acquired bullous disease were studied by direct immunofluorescence. Multiple jejunal biopsies were examined as well as tissue antigens (HLA-andthcDRw3 B cell allo-antigen). Juvenile dermatitis herpetiformis (JDH) was diagnosed in seven patients and chronic bullous disease of childhood (CBDC) in one. The use of these different laboratory techniques may make it possible to differentiate more clearly between the different chronic acquired bullous diseases seen in childhood.

The primary structure of the variable region of an amyloid-fibril protein GIL of immunoglobulin lambda-light-chain origin (AL) was determined. The AL protein obtained from the fibrils in the spleen of a 54-year-old man with primary systemic amyloidosis could be assigned to subgroup IV of the lambda variable-region sequence. About 50% of the protein was found to be truncated in the N-terminus and lacked the first six amino acid residues. The polypeptides consisted of about 146 amino acid residues and contained traces of carbohydrate. An acceptor site for N-glycosylation was found in positions 90-93, but no glycopeptide could be isolated. Comparison of the amino acid sequence of AL protein GIL with that of the only Bence-Jones protein of subgroup IV previously studied revealed a sequence homology of 89%. A similar comparison made with other AL proteins gave sequence homologies below 66%.

The amino acid sequence of the variable region of a carbohydrate-containing amyloid-fibril protein MOL of immunoglobulin-light-chain type (AL) was elucidated. The sequence determination involved cleaving the protein with CNBr, BNPS-skatole, thermolysin and trypsin. The sequenced protein consisted of about 130 amino acid residues; however, gel-filtration and N-terminal analysis studies revealed AL proteins ranging in Mr from about 10,000 to 25,000. The oligosaccharide chain was found to be bound in the hypervariable region. By sequence homology to other lambda chains the AL protein MOL was shown to be of the V lambda III subgroup.

The amino acid sequence of an amyloid-fibril protein of immunoglobulin light-chain type (AL) was elucidated. The sequence determination involved digesting the protein with trypsin, thermolysin and pepsin. The protein was found to consist of 154 amino acid residues and is thus missing about half of the constant region of a light chain. A certain heterogeneity in the length of the polypeptide was observed in the C-terminal region. The amino acid sequence from CDR (complementary-determining region) 1 and FR (framework region) 3 indicated an oligoclonal origin of the protein. By comparing the primary structure of protein AR with other lambda- and even kappa-chains, it was revealed that protein AR had an insertion of two residues of aspartic acid, namely residues 68 and 69, which has not been reported previously in light chains. The overall sequence homology in the variable region showed that protein AR is more similar to V lambda V than to the other subgroups [Kabat, Wu & Bilofsky (1979) Variable regions of Immunoglobulin Chains, Medical Computer Systems, Bolt, Beranek and Newman, Cambridge, MA].

Amyloid-related serum protein (SAA) was analysed by radioimmunoassay in 32 patients with cystic fibrosis, and compared with other acute phase reactants and lung function. The level of SAA showed significant correlation with impaired lung function due to active Pseudomonas aeruginosa infection, and also to C-reactive protein. SAA seemed to correlate better to the presence of bacteria in sputum than C-reactive protein. Ten of the patients received extensive antibiotic treatment for their pulmonary infection, and falling serum levels of SAA paralleled the clinical response to treatment. Thus the concentration of SAA in these patients was a valuable guide for the selection of patients for antibiotic treatment as well as a good parameter of the response to therapy.

In a retrospective study of 148 patients with well-defined ankylosing spondylitis (AS), psoriatic arthritis (PSA) or reactive arthritis (ReA) an 11% prevalence of idiopathic hematuria, proteinuria, or cylinduria was found in the former two groups. None of the patients with ReA had unexplained pathological urinary findings. Such findings were associated with raised ESR and presence of peripheral arthritis in AS and with the duration of disease in PSA. No patient lacking sacroiliitis showed pathological urinary findings. We believe that such findings may reflect nephropathy associated with AS and PSA.

Amyloid-related serum protein (SAA) was studied with a double immunodiffusion method. Only 2 of 21 patients with inherited systemic amyloidosis and lattice corneal dystrophy had elevated SAA levels in their sera. Several pseudo-exfoliation patients had elevated levels of SAA, but it was not possible to differentiate an age-related elevation of SAA from that associated with this disease. In addition, SAA was found in the sera of many groups of patients with acute viral infections, including 10 of 11 patients with measles and 7 of 11 persons vaccinated against rubella. Elevation of SAA protein appeared in the serum before the 6th day after the vaccination, had its peak value between days 6 and 12, but was absent already on the 20th day. In this relation the SAA protein appears to behave as an acute-phase reactant.

Organ cultures and primary cell cultures were established from synovial tissue collected from patients with rheumatoid arthritis. Hyaluronic acid measured by the incorporation of [3H]glucosamine into the polysaccharide was found to be synthesised in the cultures immediately after transfer from in-vivo to in-vitro conditions. This was in contrast to the primary cultures established from cells isolated from normal joints. The latter cells did not synthesise any detectable hyaluronate. 90-100% of the cells in primary culture were found to be esterase positive, indicating their macrophage nature. The molecular weight of the hyaluronate produced by the pathological cells was low (approximately 50 000) compared with the molecular weight of hyaluronate found in joint fluid from normal or rheumatoid joints. Cell lines of fibroblasts established from rheumatoid joints and studied after four or seven passages also produced hyaluronate of low molecular weight. It is known that similar cell lines from normal joints produce a high molecular weight polymer.

The concentrations of immunoreactive vasoactive intestinal polypeptide (ir-VIP), immunoreactive pancreatic polypeptide (ir-PP), ir-somatostatin, and ir-secretin were measured in serum and synovial fluid from patients suffering from various inflammatory joint diseases. One group of patients were not taking any medication, while another group received anti-inflammatory treatment at the time of sampling. High levels of ir-VIP in the synovial fluid were observed in the untreated group of patients, and the concentration of ir-VIP in the synovial fluid was significantly higher than in parallel serum samples. On the other hand, no significant differences in the concentrations of the other peptides were observed either between serum and synovial fluid or between the two groups of patients. It is suggested that VIP is released locally at the inflammatory site and that VIP may be of significance in inflammatory disorders.

In 9 families of which at least two members were affected by rheumatoid arthritis (RA), no specific combination of HLA genes, i.e., HLA haplotype was found to be associated with transmission of disease susceptibility. The results suggested an important role of HLA-DR4 in the etiology of RA, irrespective of other HLA markers. In addition, it may be concluded that genetic markers other than DR4 may act together with this HLA antigen in determining which individuals are at risk of developing this rheumatic disorder.

Lymphocytes separated from synovial fluid in rheumatoid arthritis by means of gradient centrifugation were characterized with regard to B- and T-lymphocyte properties. Membrane-bound Ig detectable with immunofluorescence technique was utilized as a marker of B-lymphocytes, while the ability to bind sheep erythrocytes and form rosettes was interpreted as a T-lymphocyte characteristic. In 9 out of 18 patients studied no Ig-positive lymphocytes were found in synovial fluid, while the remaining 9 patients had 1% or less. Appropriate control experiments indicated that the absence of membrane-bound Ig on lymphocytes was not due to in vivo induced redistribution with subsequent endocytosis of Ig receptors. The percentages of B-lymphocytes in peripheral blood from patients (mean 11% and range 3–19%) were not significantly different from those of 54 normal individuals (mean 10% and range 3–22%). Rosette-forming lymphocytes were found in synovial fluid of 11 patients studied, with mean 29.6% and range 19.0–60.2%, which are significantly higher than the corresponding values in peripheral blood, 22.7% and 0.9–41.1%. The latter values were also significantly higher than those of peripheral blood from 32 normals (mean 14.8% and range 0.9–34.7%). The increased proportions of T-lymphocytes in synovial fluid in rheumatoid arthritis in contrast to the absence or very low numbers of B-lymphocytes may indicate an important role for the former in the pathogenesis of rheumatoid inflammation.

Amyloid fibrils from two cases of cancer-associated, systemic amyloidosis with renal cell carcinoma and mesothelioma as the respective underlying disorders were studied. The immunochemical studies suggested strongly that amyloid A comprised a principal fibril component in both cases of cancer-associated amyloidosis. This was definitively proven by amino acid sequence analyses, which revealed structural homology between a purified subcomponent of the amyloid fibrils from both of the two cases of cancer-associated amyloidosis and previously sequenced amyloid A proteins. The chemical composition of the amyloid fibrils from systemic amyloidosis associated with cancer thus corresponded to that seen in amyloidosis reactive to inflammatory diseases and Hodgkin's disease. Amyloid proteins of immunoglobulin light chain type, which are found associated with myelomatosis, macroglobulinemia, and idiopathic (primary) amyloidosis, were not found in the two amyloid preparations. Renal cell carcinoma appears to be an effective stimulator of amyloid formation, while only one case of amyloidosis associated with mesothelioma has been reported previously.

Five patients with interstitial nephritis who presented with a variety of clinical profiles were studied with particular emphasis on documentation of the cellular types of potentially immunocompetent lymphocytes and mononuclear cells present within interstitial renal infiltrates. Immunohistologic studies coupled with conventional light and electron microscopic observations indicated that most mononuclear cells making up renal interstitial infiltrates were T cells. Some chronic inflammatory cell foci within renal interstitium were characterized by clusters of Ia antigen-positive T cells considered to be markers for activated lymphocytes. B cells were present in very small proportions (5 percent or less). The profile of immunocompetent cells present in lesions of interstitial nephritis suggests a major role for cell-mediated immunity in this disorder. Increase in tissue lymphocytes of the T gamma subclass with receptors for the Fc portion of immunoglobulin G (IgG) also suggests local activation of intrinsic suppressor cell mechanisms.

The frequency of HLA antigens has been investigated in patients with definite rheumatoid arthritis (RA) who lacked characteristic erosive radiographic changes that we called nonerosive rheumatoid arthritis ( NERA ). The frequency of HLA-DR4 in patients with NERA was significantly lower than that in classical, erosive RA. A normal frequency of HLA antigens was also found in patients with palindromic rheumatism (PR). Those of the PR patients who however, developed RA during followup, carried HLA-DR4. The patients with PR, NERA and RA who had familial RA demonstrated increased frequency of HLA-DR4.

Thirteen families were studied for the frequency of HLA-B27 and allotypes of the components of complement, C2, C4 and Bf. The 13 probands all suffered from definite ankylosing spondylitis (AS) as defined by the New York criteria. The results showed that HLA-B27 positive haplotypes in AS patients possessed different complement allotypes. Thus, it is postulated that the gene conferring predisposition to the development of AS is either HLA-B27 itself or another gene in very close proximity to the HLA-B locus.

Serum IgE concentrations were elevated in thirty-seven out of sixty-seven patients (55%) with acute or chronic liver disease of widely differing aetiology. The mean IgE concentrations in these patients showed an eight-fold increase above that observed in control subjects. Increased IgE levels in patients with liver disease occurred in the absence of eosinophilia, clinical evidence of atopy or other known causes of IgE elevation. No IgE-containing plasma cells were detected in the liver biopsies from thirty-two of the sixty-seven patients tested. Peripheral blood T cells were significantly decreased from normal in the patients with liver disease, but no correlation emerged between serum IgE levels and absolute peripheral blood T-cell numbers. These findings emphasize the importance of liver disease as a significant cause of serum IgE elevation.

In spite of an apparent decrease in its occurrence during the last 2-3 decades, amyloidosis associated with rheumatoid arthritis is a significant cause of increased morbidity and early death in both juvenile- and adult-onset rheumatoid arthritis (RA). Like other forms of reactive amyloidosis, the amyloid fibrils associated with rheumatoid disorders are of the protein AA type, and the acute phase reactant SAA, which is complexed to high density lipoprotein in serum, is its putative precursor. Raised SAA appears to be one of the prerequisites for the development of reactive, AA amyloid. Effective treatment of the underlying disorder i.e. rheumatoid arthritis, which lowers the levels of SAA is, therefore, recommended both as a prophylactic and therapeutic measure against reactive amyloidosis. As renal disease is the most severe and life-threatening consequence of reactive amyloidosis, both hemodialysis and renal transplantation are also to be considered in such patients.

Frozen sections of kidney tissue from 12 patients with systemic lupus erythematosus were examined for the expression of oncogene proteins. Polyclonal rabbit antibody to c-myc peptide or to whole 65,000 D c-myc protein, was used to identify c-myc protein within tissue sections. Patterns of nuclear staining in the Hep-2 cell line were similar to those seen with monospecific human SLE sera showing anti-Sm reactivity. In addition c-myc staining was not abolished by prior incubation of tissue sections with human serum containing anti-Sm antibodies. Five of 12 kidney biopsy tissues from patients with systemic lupus erythematosus (SLE) showed positive speckled c-myc protein staining within nuclei of monocyte/macrophage cells of glomerular tufts. Positive staining was in all instances completely abolished by prior absorption of anti-c-myc antibody with c-myc protein. No c-myc protein was identified within SLE immune complex deposits.

Seventy-four hospitalized patients with ankylosing spondylitis (HOSP AS) were compared clinically with 27 AS patients found in an epidemiological study (EPI AS). The distribution of radiographic changes, initial symptoms and age at onset of AS, frequency of HLA-B27 and acute anterior uveitis were similar in the 2 groups. The EPI AS patients had less restricted spinal and chest mobility than the hospitalized patients. Restriction of mobility thus appears to be an important factor for referral of patients with AS to hospital. A higher frequency of employment among EPI AS patients was found.

Human amyloid-related protein SAA has been prepared and purified by gel filtration, ion-exchange and affinity chromatography techniques. It was shown that SAA, even after extensive purification, is an electrophoretically heterogeneous protein. In addition, prealbumin and fragments of albumin were detected in the SAA preparation. Most of the SAA molecules and the fragments of albumin were present in a free form, but some SAA was also found to be complexed with albumin fragments.

Amyloid obtained from the myocardium of a patient (Han) with familial amyloid cardiomyopathy of Danish origin was studied. Gel filtration and electrophoresis of purified and denatured amyloid fibrils Han revealed various fractions ranging in mol. wt from 40,000 to 8,000 daltons. Amyloid Han and fractions reacted with an antiserum against amyloid Han showing a reaction of identity with each other; partial identity between Han and human pre-albumin was observed, while no reaction was seen with AA or AL proteins. Cardiac tissue sections from Han showed reactivity with antisera to amyloid Han, pre-albumin and protein AP, but not with anti-AA or anti-AL in indirect immunofluorescence. Amino acid composition and sequence studies of a protein fraction of amyloid Han with mol. wt 15,000 daltons confirmed the structural relationship with pre-albumin.

Forty-four females and 82 male patients with ankylosing spondylitis (AS) were compared in a retrospective study. No differences were found with respect to age at onset of disease, initial symptoms, work performance or peripheral joint involvement. Furthermore, males and females did not differ in restriction of spinal mobility, chest expansion, frequency of acute anterior uveitis or mean concentration of IgA. Males had significantly higher frequency of elevated C-reactive protein whereas mean erythrocyte sedimentation rate showed no such difference.

In this study of protein composition of amyloid fibrils isolated from eight patients representative of the spectrum of amyloidosis found in Papua New Guinea has been investigated. All fibril preparations, including three from patients with amyloidosis secondary to lepromatous leprosy and one from an unusual juvenile case of primary amyloidosis, contained the non-immunogobulin amyloid protein, protein AA. However, only 44% of thirty-six amyloid patients had detectable levels of the protein AA-related serum component, protein SAA. Alkali-degraded material from each of the fibril preparations failed to react in double immunodiffusion test with antiserum to the amyloid-related light chain VgammaV, but evidence was found for this immunoglobulin light chain-specificity in the serum of one patient.

The amyloid fibril is the unique component of amyloid substances. Some amyloid fibrils (i.e. AL amyloid) are made up by homogeneous immunoglobulin light chains, and such fibrils are related to systemic and localized primary amyloidosis and amyloidosis associated with myelomatosis and Waldenstrøm's macroglobulinaemia. More lambda than kappa light chain proteins make up the amyloid in these cases, and it appears that lambda-chains are more prone to fibril formation than kappa-chains. Immunoglobulins are thus the precursor protein for AL amyloid, which shows that primary amyloidosis belongs to the plasma cell dyscrasias. Amyloid infiltration of the heart and the kidneys accounts for the most severe clinical consequences of AL amyloidosis. In addition, peripheral neuropathy, carpal tunnel syndrome, macroglossia, skin affections, amyloid arthropathy and autonomic disturbances (i.e. orthostatic hypotension) are characteristic features of the disease. Involvement of parenchymal organs (kidneys, liver, spleen, gastrointestinal tract and endocrine glands) are common to systemic AL amyloidosis and secondary amyloidosis. As protein AA is the major fibril constituent of secondary amyloid, this form of amyloid disease is not related to immunoglobulins. Like other forms of plasma cell dyscrasia, patients with AL amyloidosis are usually treated with cytotoxic drugs and corticosteroids, however, the prognosis is very poor with a reported survival time after diagnosis of less than two years.

During a 24 h infusion of highly diluted thromboplastin (Simplastin), high plasma levels of fibrinogen and of factor V, and a moderate drop in thrombocyte count were observed. In addition, a positive ethanol test was consistently found. At autopsy, immunofluorescent technique revealed deposits of fibrinogen-like material in the kidneys, whereas light microscopy gave equivocal results. No deposits were found in control animals by either technique. The associated finding of a positive ethanol test and deposited fibrinogen-like material by immunofluorescent technique suggests that the ethanol test may be of value for the diagnosis of low-grade disseminated intravascular coagulation.