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Background/objective The criterion standard for anti-topoisomerase I antibody (anti-topo I antibody) testing in systemic sclerosis (SSc) uses immunodiffusion (ID) techniques, but enzyme-linked immunosorbent assay (ELISA) and multiple-bead technology are often used in current settings to save time and cost. Our aim was to assess the performance of the multiple-bead assay, ELISA, and ID testing methods. Methods We conducted a retrospective study of patients at the University of Michigan whose extractable nuclear antigen 10 autoantibody panel tested positive for the anti-topo I antibody by multiple-bead technology during a 1-year period. All samples positive by multiple-bead assay were sent to the RDL Laboratories and reflexed for ELISA, and all anti-topo I antibodies positive by ELISA were further tested by ID. Clinical data were reviewed by a rheumatologist and assessed for presence of SSc. Data were analyzed via frequency tables. Results Approximately 9500 extractable nuclear antigen 10 panels were ordered by physicians at the University of Michigan. Of these, 129 patients were positive for the anti-topo I antibody by multiple-bead assay, 51 were positive by multiple-bead assay and ELISA, and 21 were positive by multiple-bead assay, ELISA, and ID. We found that 26.4% of patients positive by multiple-bead assay, 47.1% positive by multiple-bead assay and ELISA, and 95.2% positive by multiple-bead assay, ELISA, and ID had SSc. Conclusions Multiple-bead assays have a high rate of false-positive results for the anti-topo I antibody in patients without clinical evidence of SSc. A stepwise approach of confirmation of positive multiple-bead assay results using both ELISA and ID improves the predictive value of antibody testing for the diagnosis of SSc.

Sporadic inclusion body myositis (IBM) is the most common acquired myopathy affecting patients over age 50. The discovery of an autoantibody directed against a 43–44 kD protein (anti-cytosolic-5′-nucleotidase 1A or anti-cN1A) has provided support for the hypothesis of an immune-mediated pathogenesis. Previous studies have reported variable test sensitivity and specificity, and inconsistent results on the predictive value. In our cohort of 40 patients with clinico-pathologically or clinically defined IBM, we found the sensitivity of the anti-cN1A antibody test to be 50%. Comparing characteristics for test positive and test negative groups, we found that patients in our cohort testing positive for the anti-cN1A antibody were significantly more likely to be older than age 60 years at symptom onset. We found no positive association between anti-cN1A reactivity and other clinical, laboratory, and muscle histopathologic findings. Based on all clinical studies published to date including the present, the anti-cN1A antibody test shows high diagnostic specificity, moderate sensitivity, and a low predictive value in regards to age of onset, disease severity and other associated clinicopathological findings.

Purpose Sporadic inclusion body myositis (sIBM) is an autoimmune degenerative disease of the muscle, with inflammatory infiltrates and inclusion vacuoles. Its pathogenesis is not fully understood and the diagnosis is hampered by its imprecise characteristics, at times indistinguishable from other idiopathic inflammatory myopathies such as polymyositis and dermatomyositis. The diagnosis may be assisted by the detection of autoantibodies targeting Mup44, a skeletal muscle antigen identified as cytosolic 5′-nucleotidase 1A (cN-1A, NT5C1A). A novel standardized anti-cN-1A IgG ELISA was developed and its diagnostic performance was evaluated by two reference laboratories. Methods Recombinant human full-length cN-1A was expressed and purified, and subsequently utilized to set up a standardized ELISA. To evaluate the novel assay, laboratory A examined sera from North American patients with clinically and pathologically diagnosed definite sIBM (n = 17), suspected sIBM (n = 14), myositis controls (n = 110), non-myositis autoimmune controls (n = 93) and healthy subjects (n = 52). Laboratory B analyzed a Dutch cohort of definite sIBM patients (n = 51) and healthy controls (n = 202). Results Anti-cN-1A reactivity was most frequent in definite sIBM (39.2–47.1%), but absent in biopsy-proven classic polymyositis or dermatomyositis. Overall diagnostic sensitivity and specificity amounted to 35.5 and 96.1% (laboratory A) and 39.2 and 96.5% (laboratory B). Conclusions Anti-cN-1A autoantibodies were detected by ELISA with moderate sensitivity, but high specificity for sIBM and may therefore help diagnose this infrequent and difficult-to-diagnose myopathy. The novel anti-cN-1A IgG ELISA can improve and accelerate the diagnosis of sIBM using sera where muscle biopsy is delayed or unfeasible.

To identify peripheral blood autoantibody and cytokine profiles that characterise clinically relevant subgroups of patients with early rheumatoid arthritis using arthritis antigen microarrays and a multiplex cytokine assay.Serum samples from 56 patients with a diagnosis of rheumatoid arthritis of6 months' duration were tested. Cytokine profiles were also determined in samples from patients with psoriatic arthritis (PsA) and ankylosing spondylitis (n = 21), and from healthy individuals (n = 19). Data were analysed using Kruskal-Wallis test with Dunn's adjustment for multiple comparisons, linear correlation tests, significance analysis of microarrays (SAM) and hierarchical clustering software.Distinct antibody profiles were associated with subgroups of patients who exhibited high serum levels of tumour necrosis factor (TNF)alpha, interleukin (IL)1beta, IL6, IL13, IL15 and granulocyte macrophage colony-stimulating factor. Significantly increased autoantibody reactivity against citrullinated epitopes was observed in patients within the cytokine "high" subgroup. Increased levels of TNFalpha, IL1alpha, IL12p40 and IL13, and the chemokines eotaxin/CCL11, monocyte chemoattractant protein-1 and interferon-inducible protein 10, were present in early rheumatoid arthritis as compared with controls (p0.001). Chemokines showed some of the most impressive differences. Only IL8/CXCL8 concentrations were higher in patients with PsA/ankylosing spondylitis (p = 0.02).Increased blood levels of proinflammatory cytokines are associated with autoantibody targeting of citrullinated antigens and surrogate markers of disease activity in patients with early rheumatoid arthritis. Proteomic analysis of serum autoantibodies, cytokines and chemokines enables stratification of patients with early rheumatoid arthritis into molecular subgroups.

Objective To test the hypotheses that some plasmin-reactive anticardiolipin antibodies (aCL) may bind to tissue plasminogen activator (tPA) and that some of the tPA-reactive aCL may inhibit tPA activity. Methods We studied the reactivity of 8 patient-derived monoclonal aCL with tPA and examined the presence of IgG anti-tPA antibodies in patients with the antiphospholipid syndrome (APS). The effects of the reactive monoclonal aCL on the activity of tPA were also examined. Results Six patient-derived plasmin-reactive monoclonal aCL bound to tPA. Analysis of plasma samples revealed that 10 of 80 APS patients (12.5%) and 1 of 81 systemic lupus erythematosus patients (1.2%) had antibodies against fibrin-associated tPA, based on a cutoff value equal to the mean + 2SD of the level in 28 normal subjects. Of the 6 tPA-reactive monoclonal aCL, 2 of them (CL1 and CL15) inhibited tPA activity. Conclusion Some of the plasmin-reactive aCL in APS patients may bind to tPA. Of the tPA-reactive aCL, some (such as CL1 and CL15) may inhibit tPA activity and, thus, may be prothrombotic in the host.

Previous studies have documented humoral and cell-mediated immunologic defects in patients with vitiligo.This 24-week study assessed the efficacy and safety of tacrolimus 0.1% ointment in patients with generalized vitiligo as well as the pretreatment and post-treatment expression of cytokines in the depigmented and normal skin of patients compared with controls.Twenty-three patients were enrolled in this investigation, and 19 patients completed the study; 8 were male and 11 were female. Fifteen age-, race-, and sex-matched control subjects were also included. Patients were treated with tacrolimus 0.1% ointment applied twice daily. Repeat evaluations were performed at 4, 8, 12, 16, 20, and 24 weeks. Three-millimeter punch biopsy specimens were taken from the depigmented, non-sun-exposed skin and adjacent normal skin of patients at baseline and 24 weeks, and from normal, non-sun-exposed skin of controls. Cellular messenger RNA expression for interleukin 2 (IL-2), IL-4, IL-10, tumor necrosis factor alfa (TFN-alpha), and interferon gamma (IFN-gamma) were determined by real-time quantitative polymerase chain reaction.At 24 weeks, 17 of 19 patients (89%) achieved varying levels of repigmentation. There was a statistically significant decrease in overall disease severity scores at 24 weeks. Thirteen patients (68%) had greater than 75% repigmentation of face and/or neck lesions. Signs and symptoms of irritation were minimal. At baseline, compared with healthy controls, vitiligo patients demonstrated a statistically significant increase in the expression of IFN-gamma in involved and adjacent uninvolved skin (P=.05 and P=.02, respectively); significantly increased TNF-alpha expression in involved and uninvolved skin (P=.01 and P=0.02, respectively); and significantly increased IL-10 expression in involved and uninvolved skin (P=.01 and P=.04, respectively). Posttreatment, TNF-alpha expression decreased in the depigmented and adjacent uninvolved skin (P.001). There was no statistically significant change in IL-10 or IFN-gamma posttreatment. These data suggest that tacrolimus 0.1% ointment is a safe and effective therapy for patients with vitiligo. It further suggests that an imbalance in local cytokine expression may play a role in the pathogenesis of vitiligo. Suppression of TNF-alpha after topical tacrolimus application may be associated with repigmentation of vitiligo.

OBJECTIVE To assess the efficacy of pulse/synchronization cyclophosphamide/apheresis in patients with proliferative lupus nephritis. METHODS Eighteen patients with Class III or IV renal biopsies and chronicity indices

Of 500 patients with systemic lupus erythematosus observed at our center, 150 fulfilled criteria for lupus nephritis. Of these 150 patients, 91% were female, and 67% were white. The mean age of onset was 26.2 years, and the mean follow-up duration was 11.7 years. Biopsies (n = 142) performed on 107 patients showed the following World Health Organization (WHO) class distribution: class I, n=1; class II, n=13; class III, n=19; class IV, n=69; class V, n=17; class VI, n=8; and class not determinable, n=15. Ninety-five patients were nephrotic. Therapeutic intervention courses given to all patients (n = 356) included parenteral (IV) cyclophosphamide (n = 58), high-dose oral steroids (n = 126), pulse steroids (n = 49), apheresis (n = 39), azathioprine (n = 43), oral cyclophosphamide (n = 5), nitrogen mustard (n = 27), and chlorambucil (n = 6). In addition to examining the course of disease for various subsets, various predictors for fatality and end-stage renal disease (ESRD) were analyzed. Descriptive data for the short-term response to five therapies are provided for the complete patient sample, proliferative disease, and nephrotic syndrome. Twenty patients died, primarily from cardiovascular complications and sepsis, with 97% and 92% 5-and 10-year survival rates, respectively. Twenty-nine were dialyzed, and 11 were transplanted. Risk of ESRD by WHO class at 5 years was as follows: class III, 0%; IV, 9%; V, 16% ( P = .04 for class V v other patterns). Blacks had a higher risk of death and ESRD. Class III was clearly associated with a lower risk of death and ESRD than class IV or V. Ten-year probabilities of ESRD are 25% for nephrotic patients versus 4% for nonnephrotic patients. IV cyclophosphamide and high-dose oral steroids both appeared to be beneficial for proliferative disease and nephrosis. Treatment with pulse steroids (given with cytotoxic drugs 85% of the time) was associated with nephritis improvement.

The influence of silicone breast implants on patients who develop systemic lupus erythematosus (SLE) and scleroderma are not known. Thirty SLE and 15 scleroderma patients who developed their diseases after under-going augmentation mammoplasty with silicone breast implants were studied. Clinical, laboratory, and treatment features for SLE were compared with age-, sex-, and race-matched controls from our 570-patient cohort. Comparisons were also made with a 75-patient university medical center scleroderma cohort. The SLE implant patients had milder disease but greater frequencies of cutaneous findings, cognitive impairment, and fibromyalgia than SLE patients without implants (p < 0.05). The scleroderma implant group also tended to have milder disease. Of the 45 patients, 26 had their implants removed. Subjective, clinical, and serologic remission after explantation occurred in two of the patients (both with SLE). Twenty-four additional patients had transient subjective improvement or no improvement after explantation; one patient developed malignant hypertension and a scleroderma kidney weeks after explantation.In conclusion, most lupus and scleroderma patients with implants experienced milder, although apparently classical, disease. Dramatic changes in disease course occurred in 3 of the 26 patients immediately after explantation. Because idiopathic disease patients have a 2-10% spontaneous remission rate, more time will be needed to evaluate the natural disease course in the remaining explanted patients.

Immunoassay-based anti-nuclear antibody (ANA) screens are increasingly used in the initial evaluation of autoimmune disorders, but these tests offer no “pattern information” comparable to the information from indirect fluorescence assay-based screens. Thus, there is no indication of “next steps” when a positive result is obtained. To improve the utility of immunoassay-based ANA screening, we evaluated a new method that combines a multiplex immunoassay with a k nearest neighbor (kNN) algorithm for computer-assisted pattern recognition. We assembled a training set, consisting of 1,152 sera from patients with various rheumatic diseases and nondiseased patients. The clinical sensitivity and specificity of the multiplex method and algorithm were evaluated with a test set that consisted of 173 sera collected at a rheumatology clinic from patients diagnosed by using standard criteria, as well as 152 age- and sex-matched sera from presumably healthy individuals (sera collected at a blood bank). The test set was also evaluated with a HEp-2 cell-based enzyme-linked immunosorbent assay (ELISA). Both the ELISA and multiplex immunoassay results were positive for 94% of the systemic lupus erythematosus (SLE) patients. The kNN algorithm correctly proposed an SLE pattern for 84% of the antibody-positive SLE patients. For patients with no connective tissue disease, the multiplex method found fewer positive results than the ELISA screen, and no disease was proposed by the kNN algorithm for most of these patients. In conclusion, the automated algorithm could identify SLE patterns and may be useful in the identification of patients who would benefit from early referral to a specialist, as well as patients who do not require further evaluation.

Hydroxychloroquine has several less well-known actions that may have clinical relevance in treating systemic lupus erythematosus (SLE). (1) Hydroxychloroquine has a possible antithrombotic action. It is a platelet inhibitor and appears to decrease the risk of thromboembolism in patients with anticardiolipin antibodies. (2) Hydroxychloroquine is associated with lower serum cholesterol and low-density lipoprotein levels compared to those present in patients who are taking corticosteroids but not antimalarials for SLE. (3) It may also decrease abnormal levels of cytokines. Interleukin-6 (IL-6), soluble CD8 and soluble IL-2 receptors (sIL-2R) are lower in patients taking antimalarials compared to those on corticosteroids alone or on neither medication. Serum levels of CDS and sIL-2R decrease after 6 weeks of hydroxychloroquine treatment. These findings may help explain the favorable response of SLE patients treated with antimalarials.

Objectives: The treatment of lupus membranous nephritis (LMN), a lupus subset that carries a high morbidity, is unsatisfactory. We report our experience in treating LMN with the immunosuppressive drug cyclosporine (CYS). Methods: We treated 10 patients with systemic lupus erythematosus fulfilling ACR criteria with CYS for at least 12 months and followed renal function, serologic activity and SLEDAI scores. Patient characteristics:8 females, 2 males, 50% Caucasian, mean age 37.3 y (range 22–48), disease duration 108.7 months (range 16–216), nephritis duration 35.5 months (range 12–59), date of biopsy to date of starting treatment 10.7 months (range 0–90). The patients were started on CYS with a mean dose of 3.8 mg/kg (range 2.2–6) and followed for a mean duration of 24.8 months (range 12–59). A Medline search identified all patients with lupus who were given CYS or had LMN in articles from 1966–1999. Results: Proteinuria improved from a baseline mean of 5588 mg/24 h (range 2712–11 055) to 1404 mg/24 h (range < 150–2652). Serum albumin increased from a baseline mean of 2.8 g=100 ml (range 1.31–3.8) to a mean of 3.9 g/100 ml (range 3–4.5) at last follow-up. There was no significant change in lupus activity as measured by SLEDAI. Nephrotoxicity was common as evidenced by an increase in serum creatinine but it returned to baseline with adjustment of the dose of CYS (20% decrease in the dose of CYS for a 20% increase in serum creatinine). More antihypertensive medications were required to control the blood pressure in these ten patients at the end of the study compared to the onset (total number = 13 versus 6). Conclusion: Proteinuria and serum albumin improved in all patients on CYS. A literature review is consistent with this. Controlled studies of the use of CYS for membranous lupus nephritis would be useful.

The elevated expression of IL-6 and IL-10 may have an important role in SLE pathogenesis. IL-6 production by normal monocytes can be inhibited by IL-10, and it has been suggested that SLE monocytes are refractory to this negative signal. To examine this possibility, the effects of regulatory factors on IL-6 expression by SLE PBMC (N = 51) were compared to effects on control PBMC (N = 21). We found that (1) exogenous rIL-10 and rIL-4 mediated reduction of constitutive and lectin-induced IL-6 in monocytes of SLE patients as effectively as that of controls; (2) IL-6 mRNA decay was significantly delayed in SLE with active disease (P < 0.001); (3) adding rIL-10 or neutralizing endogenous IL-1 beta and TNF-alpha down-regulated IL-6 mainly by destabilizing IL-6 transcripts, whereas exogenous IL-4 and TGF beta 1 down-regulated IL-6 transcriptionally; (4) time kinetics and levels of IL-10 were lower than those of IL-6 and IL-1 beta. Thus, contrary to a previous report, IL-6 production by SLE PBMC responds normally to regulatory signals, and the IL-6 overexpression in SLE may be due, at least in part, to the kinetics and availability of regulatory cytokines.

Patients with silicone breast implants have been reported to have a variety of autoantibodies including antinuclear antibodies1, abnormal western blots 2,3, antibodies to silicone surface associated antigens4 and anticollagen antibodies5. Reports of the prevalence of antinuclear antibodies have ranged from 20% to as high as 58%,6,7,8,9. We hypothesized that this wide range may be due to practice site and geographic differences or small sample size and we will therefore report data on over 3000 symptomatic women. Recently Bridges reported a high prevalence of antinuclear antibodies in patients with fibromyalgia using a Hep2 technique 10. We hypothesized the increased prevalence of antinuclear antibodies in symptomatic women with breast implants could not be explained by an increased prevalence of fibromyalgia. Clinicians have found a high prevalence of sicca symptoms in patients with silicone breast implants 10. We hypothesized that these sicca symptoms would not be associated with classic autoantibodies of antiRo and antiLa.

Five hundred seventy lupus erythematosus patients observed in a private practice between 1980 and 1989 were surveyed. Fifty-five percent were diagnosed after 1980. Five hundred three fulfilled criteria for systemic lupus erythematosus ( [SLE]; 464 idiopathic, 23 overlap, 16 drug-induced) and 67 had biopsy-documented cutaneous (discoid) lupus. In the idiopathic SLE group, symptoms began at a mean age of 31 years and patients were observed for a mean of 6 years. Findings in idiopathic SLE patients were (1) 27% have a family history of autoimmune disease; (2) nephritis patients without nephrotic syndrome rarely develop renal failure (4%); (3) nephrotic syndrome patients are relatively cyclophosphamide-resistant; (4) organ-threatening disease is present in 54%; and (5) 13% of women who become pregnant are recurrent aborters and 26% never conceive. In an analysis of cohort data, 5- and 10-year survivals were 97% +/- 2% and 93% +/- 3%, respectively. Additionally, men and patients with renal disease or thrombocytopenia had a poorer prognosis. Blacks had similar clinical findings and survival to whites. Approximately 50% of deaths were from active disease and 50% from complications of therapy. Prolonged survival has resulted from new diagnostic procedures and serologic tests, and improved antibiotics and antihypertensive agents, as well as more efficacious treatment modalities.

purpose: The effects of hydroxychloroquine (HCQ) on serum levels of cholesterol, triglycerides, and high- (HDL) and low-density lipoprotein (LDL) were studied in patients with rheumatoid arthritis or systemic lupus erythematosus. patients and methods: A total of 155 women were divided into the following treatment groups: Group A: patients taking HCQ and no steroids (n = 58); Group B: patients taking steroids and no HCQ (n = 35); Group C: patients receiving both HCQ and steroids (n = 18); and Group D: patients receiving neither HCQ nor steroids (n = 44). results: HCQ therapy had a high statistical association with low serum levels of cholesterol (181 mg/dL; p=0.0006), triglycerides (106 mg/dL; p=0.0459), and LDL (101 mg/dL; p=0.0004), irrespective of concomitant steroid administration. The HCQ-treated group (A) had lower cholesterol (181 mg/dL; p=0.0039) and LDL (101 mg/dL; p=0.007) levels than those receiving neither HCQ nor steroids (205 mg/dL) and 128 mg/dL) (Group D). No HDL differences were observed. conclusion: The effects of HCQ do not appear to be due to changes in diet or weight, and the drug was well tolerated. Although the mechanism of cholesterol lowering by HCQ is not known, this drug deserves further investigation for its lipid-lowering properties.

The effects of cholecystectomy on the hepatic secretion rates of biliary lipids and the relative lipid composition of hepatic bile were examined in 8 American Indian patients with cholesterol gallstones. Using a marker dilution technique, the hepatic secretion rates of cholesterol, bile acids, and phospholipids were measured during continuous duodenal infusion of formula before and several months after cholecystectomy. Before surgery, the Indian patients with gallstones secreted hepatic bile that was more lithogenic than that in a group of white women without stones. When bile was sampled under identical conditions after cholecystectomy, there was no change in biliary lipid composition or in hepatic secretion rates. Thus, cholecystectomy apparently does not correct the defect leading to lithogenic bile in these patients.

Detailed analysis of the progressive roentgenographic changes found in complete serial skeletal surveys of 2 men with multicentric reticulohistiocytosis (MR) have been correlated with pathologic findings and compared to features previously reported. The lesions of MR predominate in skin and synovium and result in the following characteristic features: (1) sharply circumscribed, rapidly progressive, strikingly bilaterally symmetric erosions spreading from joint margins to articular surfaces; (2) interphalangeal joint predominance; (3) early and severe atlanto-axial involvement; (4) disproportion between severity of joint destruction and mildness of symptoms; (5) absent or minimal periosteal reaction; (6) absent or disproportionately mild osteoporosis compared to the severity of erosions; and (7) prominent, uncalcified soft tissue nodules. Since arthritis often precedes cutaneous manifestations, careful roentgenologic evaluation may play a key role in early diagnosis.

A method has been developed for the measurement of the hourly outputs into the duodenum of biliary lipids—cholesterol, bile acids, and phospholipids—in patients with an intact biliary system. This method employs duodenal intubation with two- or three-lumen tubes; liquid formula diets are infused at constant rates, and biliary lipid outputs are estimated by marker dilution techniques. Determinations can be made with either radioactive or nonradioactive markers. In this investigation, studies of biliary lipid output were carried out for periods of 18 to 30 hr. During the first 4 to 6 hr of formula infusion outputs were high due to gallbladder bile, but thereafter a steady state in output was achieved. Thus, it was concluded that during the steady state duodenal outputs corresponded to rates of hepatic secretion. In the steady state, outputs of cholesterol ranged from 28 to 85 mg per hr for different patients, and hourly variations in output were small. Average scretion rates of bile acids were much greater (234 to 1440 mg per hr), and larger fluctuations from hour to hour could probably be explained by variable rates of reabsorption of bile acids from the distal small intestine. Hourly outputs of phospholipids, which ranged from 311 to 578 mg per hr, showed less variability than did bile acids. When outputs of cholesterol, bile acids, and phospholipids were combined, a continuous pattern of total lipid composition of bile was obtained during the period of formula feeding. It was our conclusion that this method offers several advantages for the study of the metabolism of biliary lipids in man.

Electron microscopy of synovial tissue in a patient with palindromic rheumatism showed tubular structures in the endothelial cells similar to those reported by others in the tissues of patients with other rheumatic diseases, neoplasms, infections and a variety of other idiopathic conditions.

Pernicious anemia (PA), previously considered rare among American Indians, was diagnosed in 18 Indians during a 16-yr period at the Phoenix Indian Medical Center. These patients, from ten different tribes, did not vary significantly from all adult hospital admissions in proportionate sex, tribe, or blood group distribution. The current minimum prevalence of PA for southwestern Indians is 1:514 beyond 50 yr of age and 1:293 after 60 yr of age. Despite a marked predominance of blood group 0 (81%), the Indians developed PA as frequently as other ethnic groups in which PA is strongly associated with blood group A. Their clinical and hematologic manifestations were similar to those of whites with PA. Of the 13 subjects tested immunologically, 11 demonstrated parietal cell antibodies, and six had blocking antibodies to intrinsic factor. During follow-up none developed gastric carcinoma, although this tumor— the most frequent malignancy among southwestern Indians-is correlated with PA in whites. The findings establish that PA in full-blooded south-western Indians is not rare and is clinically and immunologically similar to PA in whites.

DISODIUM etidronate has been reported to be effective in the management of calcification due to myositis ossificans progressiva1 , 2 and dermatomyositis.3 , 4 We have evaluated the efficacy of this...

THE remarkable association of the second segregant series histocompatibility antigen (HL-A) W27 with idiopathic ankylosing spondylitis is firmly established. Ninety per cent of patients with this disorder are W27 positive as compared to 8 per cent of normal white control subjects.1 , 2 W27 has also been reported with unusual frequency in anterior uveitis of diverse causes as well as in Reiter's syndrome, raising the possibility of shared pathogenetic mechanisms in these disorders.3 4 5 It is well recognized that spondylitis and a peripheral seronegative arthritis occur in a large number of patients with chronic inflammatory bowel disease.6 , 7 Although the peripheral arthropathy has several . . .

RECENTLY, an extraordinary correlation between the second-segregant series histocompatibility antigen (HL-A), W27, and a well characterized rheumatic disease, ankylosing spondylitis was reported.1 , 2 Indeed, 90 per cent of patients with the disease are W27 positive. Because ankylosing spondylitis has a strong heredofamilial distribution,3 and since the second-segregant series of HL-A antigens in certain animals is linked to immune-response genes,4 this highly important association suggests that the pathogenesis of the disease might be directly related to some aberrant, genetically controlled, cellular immune response. Reiter's syndrome is a puzzling disease with several features in common with ankylosing spondylitis — i.e., male predominance, young . . .

Presented is an unusual case of reticulum cell sarcoma whose initial manifestation was a complexity of cardiac arrhythmias which fit the description of the “sick sinus node syndrome.” In addition, the clinical presentation included pericarditis and refractory congestive heart failure. At autopsy, the sinus node and cardiac conduction system were found to be extensively involved with reticulum cell sarcoma.

Hepatic secretions of biliary lipids were determined in eight young women with cholesterol gallstones and 14 white women without gallstones. All of the gallstone patients were non-Indian; seven were white and one was black. Hourly outputs of biliary cholesterol were significantly greater in gallstone patients than in white controls. This increased cholesterol output was a major factor in the production of lithogenic bile. The greater cholesterol output in gallstone patients was apparently related to obesity. Despite an increased hepatic secretion of cholesterol, secretion rates of bile acids were relatively low in gallstone patients. However, there was considerable overlap between secretion rates of bile acids in subjects with and without stones, and it was not demonstrated that an absolute deficiency of bile acids existed in gallstone patients. Nevertheless, the contribution of an increased output of biliary cholesterol to the formation of lithogenic bile was clearly evident in our patients.

Forty subjects with psoriatic arthritis (PA) underwent HL-A tissue typing. HL-A W27 was significantly increased in psoriatic spondylitis (35%), whereas statistical significance was not reached in patients with peripheral arthritis alone, although W27 was present in a frequency greater than in controls. Psoriatic spondylitis (often asymptomatic) occurred in 57% (23 of 40) of our PA patients. Of interest, psoriatic spondylitis was more often W27 negative than W27 positive; nevertheless, W27-positive and W27-negative spondylitis was clinically and radiographically indistinguishable except that W27-positive disease occurred exclusively in males and the duration of the psoriasis was shorter when compared to W27-negative spondylitis.

In a double-blind study, patients were randomly selected for treatment using conventional doses (CD; 50 mg) or high doses (HD; 150 mg) of sodium aurothiomalate given weekly by injection. Twenty-three patients were assigned to the CD group and 24 to the HD group. Neither efficacy nor toxicity correlated with serum gold concentrations. Conventional doses were as efficacious as high doses with respect to both rapidity and degree of response. However, side effects were much more frequent and severe in the HD group. Thus there is no reason to recommend a 150 mg weekly dosage regimen.

Biliary lipid composition was determined on gallbladder bile and on hepatic bile during the diurnal cycle of feeding and fasting in American Indians with and without gallstones and in Caucasian women without gallstones. Fasting hepatic bile was consistently more lithogenic than gallbladder bile or hepatic bile obtained during feeding. Although lithogenicity was greater in Indians, even Caucasian women regularly produce more highly lithogenic bile during the fasting period, apparently because of an uncoupling of cholesterol and bile acid secretion. Although bile acids were sequestered in the gallbladder during late fasting, cholesterol secretion continued somewhat independently of bile acids, thus enhancing lithogenicity. This effect was more pronounced in Indian women, who have reduced pools of bile acids and increased cholesterol secretion. An increasing lithogenicity of hepatic bile throughout fasting might contribute to cholesterol gallstone formation if mixing in the gallbladder is incomplete...

Hepatic secretions of biliary lipids were estimated in 43 patients with and without cholesterol gallstones. Studies were carried out by a marker dilution technique employing duodenal intubation with a three-lumen tube. Hourly secretion rates of cholesterol, bile acids, and phospholipids were determined during constant infusion with liquid formula. In 17 American Indian women with gallstones, hourly outputs of biliary bile acids were significantly less than those in 7 Indian men and 12 Caucasian women without gallstones. These findings suggest that a decreased hepatic secretion of bile acids contributes significantly to the production of a lithogenic bile in Indian women. However, in Indian women with gallstones, secretion of biliary cholesterol was also significantly increased, as compared with Caucasian women without stones. Therefore, lithogenic bile in Indian women was, in most cases, due to a combined decrease in bile acid output and increase in cholesterol secretion. In an attempt to determine the mechanisms for these abnormalities, cholesterol balance studies were done in Indian women with gallstones and normal Indian men. Balance data were compared with results reported previously in non-Indian patients studied by the same techniques, and in general, Indian women showed a slight increase in fecal excretion of bile acids. Since bile acids in the enterohepatic circulation were relatively depleted in Indian women, these patients had a reduced fractional reabsorption. However, previous studies have shown that Caucasians can rapidly replenish bile acid pools in the presence of much greater intestinal losses, and it is suggested that among Indian women with gallstones, reduced secretion rates of bile acids are primarily the result of defective homeostatic regulation of bile acid synthesis. In Indian women with gallstones, at least two factors may have contributed to an increased availability of cholesterol in the liver for secretion into bile. First, cholesterol was inadequately converted into bile acids, and secondly, an increased amount of cholesterol was synthesized, as shown by the balance technique. This enhanced production of cholesterol can partially be explained by obesity, but other factors may also play a role.

A young man with diabetic ketoacidosis developed the clinical features of cerebral oedema. This resolved without specific treatment. The mortality from ketoacidosis might be reduced if the syndrome was suspected and treated earlier.

Twenty-two patients with polymyositis and dermatomyositis were treated with combined prednisone and intravenous methotrexate when moderate to high-dose cortisone alone was ineffective in c...

Excerpt To the Editor: In a recent Question of the Month (Rheumatology,Ann. Intern. Med. 68: 137, 1968) reference was made to the cause of a "biological false-positive test for syphilis" found in a...

Previously described cases of gonococcal arthritis have been secondary to genitourinary tract foci. A male patient first seen with gonorrheal pharyngitis subsequently developed gonococcal ...