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Investigators form the National Institutes of Health (NIH), in the United States, have prospectively studied 60 patients with Takayasus's arteritis over a period of 20 years. Unique observations resulted from the requirement that all patients be part of Institutional Review Board-approved standardized protocols that required periodic complete clinical, laboratory and angiographic evaluations, regardless of degree of disease activity. Patients judged to have active disease received protocol defined treatment that always included prednisone, and to which cytotoxic agents were added in the event that relapse followed tapering or withdrawal of corticosteroids. The prospective standard approach applied to this cohort has provided new insights into the presentation, course and treatment-responsiveness of Takayasu's arteritis. This article will focus on the questions raised by this study and implications for patient care.

Objective: To estimate the prevalence, annual mortality, and geographic distribution of Wegener's granulomatosis., Methods: Analysis of national vital statistics data and hospitalization data from a national survey and from all New York State inpatient facilities., Results: Between 1979 and 1988, 1,784 death certificates in the United States listed Wegener's granulomatosis as a cause of death. Nationally, an estimated 10,771 hospitalizations included Wegener's granulomatosis among the discharge diagnoses. In New York State, there were 978 hospitalizations among 571 individuals with Wegener's granulomatosis., Conclusion: The prevalence of Wegener's granulomatosis in the United States is approximately 3.0 per 100,000 persons. Clear differences in the geographic distribution of Wegener's granulomatosis are apparent when analysis consider rates of disease in individual counties. Contrary to previous reports, associations between disease exacerbations and season were not apparent.

To manage Wegener's granulomatosis (WG) effectively, the clinician must establish the diagnosis without delay, recognize variability in clinical course and severity, critically monitor disease activity, and anticipate disease-related and treatment-related morbidity. These issues represent the focus of approach to the diagnosis and treatment of WG.

Objective: To determine the efficacy of low-dose methotrexate (MTX) plus prednisone in the treatment of Wegener's granulomatosis (WG)., Methods: An open-label study of weekly low-dose MTX plus prednisone for the treatment of WG was performed. Forty-two patients who did not have immediately life-threatening disease were enrolled into the study. Outcome was determined by clinical characteristics and pathologic, laboratory, and radiographic findings., Results: Weekly administration of MTX and prednisone resulted in remission of disease in 30 of the 42 patients (71%). The median time to remission was 4.2 months. The estimated median time to relapse for all patients in whom remission was achieved was 29 months. Eight patients who had relapses were treated with a second course of MTX plus prednisone, and a second remission was induced in 6 of the 8 (75%)., Conclusion: Weekly low-dose MTX was shown in this study to be an acceptable alternative form of therapy for selected patients with WG who do not have immediately life-threatening disease or who have developed serious cyclophosphamide-associated toxicity.

The upper airway is usually the source of initial concern, but lung involvement eventually emerges. Thus, the disease is a reminder that the diagnosis of persistent upper airway problems should have more than a regional focus. Combinations of glucocorticoids and cytotoxic drugs have yielded a dramatic improvement in survival.

Objective: Currently, a reliable, noninvasive means of detecting the active vasculitic lesions of Takayasu's arteritis does not exist. Based on the cellular infiltrates seen in active lesions, we postulated that indium-111 labelled mixed leukocytes could be used to scintigraphically detect sites of active vasculitis., Methods: Fifteen In-111 mixed leukocyte scans were performed in 10 patients with Takayasu's arteritis and correlated with clinical, laboratory, and radiographic findings. Patients had either active, stable/smoldering, or inactive disease at the time when 8, 4, and 3 scans were performed, respectively., Results: Two of the 8 scans performed in patients with active disease were positive for increased vessel uptake (sensitivity = 25%). All other scans were interpreted as negative for active arteritis., Conclusion: We conclude that In-111 mixed leukocyte scans have a low sensitivity for detection of active Takayasu's arteritis.

The systemic necrotizing vasculitides represent a difficult group of diseases from a therapeutic perspective. Even with successful therapy patients often experience a high degree of disease and treatment morbidity. Refractory disease, or that which fails to respond to standard therapy, is particularly challenging. A clinical approach to several vasculitic syndromes is outlined in this article with emphasis given to therapies supported by controlled investigations and those supported by consensus opinion where available.

About 20% of patients will have a monophasic, often self-limiting illness that does not require immunosuppressive therapy. Half of all patients that require corticosteroid therapy may achieve remission and discontinue medication without relapse. The other half of this group has glucocorticoid-resistant or relapsing disease, for which cytotoxic agents may induce remission or allow for disease control with lower doses of glucocorticoids. Although it is possible, it is desirable to distinguish those features of disease for which treatment is primarily best provided by immunosuppressive agents from those abnormalities that are due to critical vascular anatomic changes for which surgery or angioplasty are more appropriate.

The literature about the treatment of giant cell arteritis (GCA) is diverse and often includes patients with polymyalgia rheumatica (PMR) who do not have concurrent features of GCA. Consequent heterogeneity has contributed to controversy in the analysis of clinical data. Nevertheless, we have critically reviewed this literature to derive a rational approach to initial and maintenance corticosteroid (CS) therapy and thus define "CS-resistant GCA." In this article, the authors review what has been written about the treatment of presumed CS-resistant disease. Although firm recommendations are lacking, the authors provide algorithms for the treatment of GCA patients who fail to respond to initial CS therapy or who require potentially toxic maintenance-dose CS therapy. A study design that may help to resolve the dilemmas that were found during our analysis is also outlined.

The vasculitides represent a heterogeneous set of disorders that differ in prognosis and response to therapy. The initial approach to diagnosis should include distinguishing primary vasculitis from nonvasculitis disease and vasculitis associated with a separate underlying process. Subsequently, an attempt should be made to recognize the specific vasculitic disorder and initiate appropriate therapy. Diagnosis should be primarily made on the basis of the clinical pattern of disease and supported by tissue pathology, angiography, or appropriate laboratory tests.

Objective: To identify the role of methotrexate (MTX) in the treatment of persistent or recurrent Takayasu arteritis that is refractory to treatment with glucocorticoids (GC) alone., Methods: An open-label pilot study of weekly low-dose MTX+GC treatment was performed. Outcome was evaluated according to clinical characteristics, laboratory abnormalities, findings on routinely performed angiographic studies, and ability to withdraw GC and MTX therapy. Eighteen patients entered the study; 2 dropped out, and 16 were followed up for a mean period of 2.8 years (range 1.3-4.8 years)., Results: Weekly administration of MTX (mean stable dose of 17.1 mg) and GC resulted in remissions in 13 of 16 patients (81%). However, 7 patients (44%) had relapses as GC was tapered to or near discontinuation. Retreatment again led to remission, and 3 of 7 patients in this group have successfully stopped GC therapy. Of those patients who achieved remission, 8 (50%) have sustained remissions of 4-34 months (mean 18 months), and 4 of this group have not required GC or MTX therapy for 7-18 months (mean 11.3 months). Three patients experienced disease progression in spite of treatment., Conclusion: About half of all Takayasu arteritis patients have chronic active disease for which GC therapy alone does not provide sustained remissions that allow withdrawal of treatment. Weekly low-dose MTX is an effective means of inducing remission and minimizing GC therapy and toxicity in most of these patients. Further long-term studies will be required to assess the durability of remission and the need for maintenance MTX therapy in this subset of Takayasu arteritis patients.

We observed systematic vasculitis (polyarteritis nodosa and Wegener's granulomatosis) in several members of 2 different families. Our experience and a review of the literature suggests that genetic factors are important but not sufficient to express clinical features of these diseases.

The following are some of the conclusions and proposals made at the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis. 1. Although not a prerequisite component of the definitions, patient age is recognized as a useful discriminator between Takayasu arteritis and giant cell (temporal) arteritis. 2. The name "polyarteritis nodosa," or alternatively, the name "classic polyarteritis nodosa," is restricted to disease in which there is arteritis in medium-sized and small arteries without involvement of smaller vessels. Therefore, patients with vasculitis affecting arterioles, venules, or capillaries, including glomerular capillaries (i.e., with glomerulonephritis), are excluded from this diagnostic category. 3. The name "Wegener's granulomatosis" is restricted to patients with granulomatous inflammation. Patients with exclusively nongranulomatous small vessel vasculitis involving the upper or lower respiratory tract (e.g., alveolar capillaritis) fall into the category of microscopic polyangiitis (microscopic polyarteritis). 4. The term "hypersensitivity vasculitis" is not used. Most patients who would have been given this diagnosis fall into the category of microscopic polyangiitis (microscopic polyarteritis) or cutaneous leukocytoclastic angiitis. 5. The name "microscopic polyangiitis," or alternatively, "microscopic polyarteritis," connotes pauci-immune (i.e., few or no immune deposits) necrotizing vasculitis affecting small vessels, with or without involvement of medium-sized arteries. Cryoglobulinemic vasculitis, Henoch-Schönlein purpura, and other forms of immune complex-mediated small vessel vasculitis must be ruled out to make this diagnosis. 6. The name "cutaneous leukocytoclastic angiitis" is restricted to vasculitis in the skin without involvement of vessels in any other organ. 7. Mucocutaneous lymph node syndrome must be present to make a diagnosis of Kawasaki disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To assess the correlation and prognostic value of antineutrophil cytoplasmic antibody (cANCA) titers with disease activity in patients with Wegener's granulomatosis (WG)., Methods: One hundred six patients with WG had serum ANCA determinations; 72 had serial titers obtained routinely at 1-3-month intervals. One hundred twelve subjects (19 of whom were healthy donors) served as controls. All serum samples were tested for cANCA by an indirect immunofluorescence technique. A prospective analysis of disease activity and cANCA values was performed. Disease activity was assessed according to clinical, laboratory, radiographic, and histopathologic findings., Results: Positivity for cANCA was a sensitive (88%) marker of active WG. However, changes in serial titers temporally correlated with a change in disease status in only 64% of patients. Furthermore, an increase in the cANCA titer preceded clinical exacerbation of disease in only 24% of patients who had been in remission or had low-grade, smoldering disease., Conclusion: A rise in cANCA titer alone should not be considered adequate evidence of an impending clinical exacerbation, and therefore does not justify initiating or increasing immunosuppressive therapy.

The following review is intended to summarize currently accepted, as well as newly appreciated therapies for the chronic systemic vasculitides. In recent years, a great deal has been learned about enhancement and inhibition of immunoinflammatory phenomena. Biological, immunomodulatory agents with focussed actions are just beginning to be tested in the clinical setting. However, until these promising approaches have been more thoroughly evaluated, it will continue to be necessary to cautiously titrate broadly immunosuppressive medications for the treatment of these disorders.

We prospectively studied and compared clinical features, treatment, course of illness, and long-term morbidity and mortality rates for Wegener granulomatosis in 23 childhood-onset patients with those of 135 adult-onset patients who were studied concurrently. Treatment was usually provided with glucocorticoids and cyclophosphamide. The mean follow-up period was 8.7 years for childhood-onset and 7.6 years for adult-onset Wegener granulomatosis. Most aspects of Wegener granulomatosis were similar in childhood-onset and adult-onset patients. Permanent morbidity from disease occurred in 86% of both groups. However, some features were significantly different. Wegener granulomatosis in childhood-onset patients was complicated five times more often by subglottic stenosis and twice as often by nasal deformity. Treatment-related permanent morbidity occurred in 22% of childhood-onset patients and 45% of adult-onset patients. After similar periods of cyclophosphamide therapy and follow-up, cyclophosphamide-related malignancies were less likely (0% vs 11%) to have developed in childhood-onset patients. Although 89% of patients treated with glucocorticoids and cyclophosphamide had remission, prolonged delay in achieving remission and relapses led in both patient groups to freedom from active disease for approximately 50% of the total patient-years. As a result, morbidity was substantial and has led to comparative studies of alternative therapies.

Wegener's granulomatosis (WG) is a multisystem inflammatory disease characterized by vasculitis, granuloma formation, and necrosis. Among 158 patients treated at the National Institutes of Health during the past 24 years, 145 (92%) had an otolaryngologic manifestation of their disease and 25 (16%) had subglottic stenosis (SGS). SGS varied from asymptomatic to life-threatening. Sixteen (80%) of 20 patients with fixed SGS required surgical intervention, including manual dilations, carbon-dioxide laser resections, and laryngotracheoplasty (LTP). LTP was performed with and without microvascular reconstruction. Thirteen of the patients required tracheostomy and all 13 were ultimately decannulated. Five patients who repeatedly failed dilations and/or endoscopic laser surgery underwent LTP. Since 1987, two patients have undergone LTP with microvascular free flaps. Both patients were subsequently decannulated. The authors' experience demonstrates that management of SGS in WG is complex, requiring individualized frequent multimodality interventions to achieve satisfactory results. Microvascular laryngotracheal reconstruction should be considered in the surgical armamentarium for patients with persistent stenoses.

Objective: To identify alternatives to daily low-dose cyclophosphamide (CYC) in the treatment of Wegener's granulomatosis (WG)., Methods: An open-label pilot study of weekly low-dose methotrexate (MTX) plus glucocorticoids (GC) for treatment of patients with WG was performed. Twenty-nine patients who did not have immediately life-threatening disease were included. Outcome was determined by clinical characteristics, pathologic findings, course of illness, laboratory and radiographic findings, and successful withdrawal of GC therapy., Results: Weekly administration of MTX (at a mean stable dosage of 20 mg) and GC resulted in marked improvement in 76% of the 29 patients. Remission was achieved in 69% of the patients, 7% improved but had intermittent smoldering disease that precluded total withdrawal of GC, and 17% had progressive disease within 2-6 months of starting the study treatment. Two patients who initially achieved remission later had relapses after GC was discontinued. Of those who remain in remission (mean followup time 14.5 months), 72% have not required GC for a mean period of 10 months., Conclusion: Although standard therapy for WG (daily CYC and GC) has dramatically improved outcome in this often-fatal disease, treatment morbidity has led to attempts to identify effective interventions that have less toxicity. Weekly low-dose MTX was shown in this study to be a feasible alternative to CYC in patients whose illness was not immediately life-threatening or in whom prior CYC treatment was ineffective or produced serious toxicity. Although these results are preliminary, they are encouraging and justify further studies in which MTX, CYC, and other alternative therapeutic approaches are compared concurrently.

A unique patient with type VIII Ehlers-Danlos syndrome and cutaneous vasculitis, resorptive osteolysis, and cardiac valvular disease is described. Collagen analyses identified morphologic and physical abnormalities of type I collagen. The patient's T lymphocytes could be propagated in vitro with type I collagen and produced a 60-kd lymphokine that bound this protein. Cellular autoimmunity to type I collagen may be responsible for this patient's intractable clinical condition.

We report the pulmonary pathologic features in 87 open lung biopsies from 67 patients with Wegener's granulomatosis (WG) who were treated at a single institution from 1968 to 1990. At the time of open lung biopsy, 48 patients (72%) had classical WG with renal involvement; 19 (28%) had limited WG without renal involvement. The pathologic features were divided into major and minor manifestations. In the 82 specimens demonstrating no infectious organism, the three major pathologic manifestations of classical WG observed were also useful diagnostic criteria and included: (a) parenchymal necrosis, (b) vasculitis, and (c) granulomatous inflammation accompanied by an inflammatory infiltrate composed of a mixture of neutrophils, lymphocytes, plasma cells, histiocytes, and eosinophils. Parenchymal necrosis was found in 84% of biopsy specimens either as neutrophilic microabscesses (65% of specimens) or as large (67%) or small (69%) areas of geographic necrosis. Areas of geographic necrosis were usually surrounded by palisading histiocytes and giant cells. Additional granulomatous lesions consisted of microabscesses surrounded by giant cells (69%), poorly formed granulomas (59%), and scattered giant cells (79%). Sarcoid-like granulomas were uncommon (4%), and in only one specimen (1%) appeared within an inflammatory lesion of WG. Vascular changes were identified in 94% of biopsy specimens. Vascular inflammation was classified as chronic (37% arterial, 64% venous), acute (37% arterial, 29% venous), non-necrotizing granulomatous (22% arterial, 9% venous), and necrotizing granulomatous (22% arterial, 10% venous). Fibrinoid necrosis was relatively uncommon (11% arterial, 6% venous). Cicatricial changes were found in arteries in 41% of biopsy specimens and in veins in 16%. Capillaritis was present in 31% of specimens. Minor pathologic lesions were commonly observed in biopsy specimens associated with classical WG lesions, but they were usually inconspicuous and not useful diagnostic criteria. These included interstitial fibrosis (26%), alveolar hemorrhage (49%), tissue eosinophils (100%), organizing intraluminal fibrosis (70%), endogenous lipoid pneumonia (59%), lymphoid aggregates (37%), and a variety of bronchial/bronchiolar lesions including acute and chronic bronchiolitis (51% and 64%), follicular bronchiolitis (28%), and bronchiolitis obliterans (31%). These minor lesions were often found at the periphery of typical nodules of WG. However, in 15 specimens (18%) a minor pathologic feature represented the dominant or major finding: pulmonary fibrosis (six specimens, 7%), diffuse pulmonary hemorrhage (six specimens, 7%), lipoid pneumonia (one specimen, 1%), acute bronchopneumonia (one specimen, 1%), and chronic bronchiolitis, bronchiolitic obliterans with organizing pneumonia (BOOP), and bronchocentric granulomatosis (one specimen, 1%).(ABSTRACT TRUNCATED AT 400 WORDS)

Wegener's granulomatosis (WG) is a small-vessel vasculitis of unknown etiology that usually involves the upper and lower respiratory tract and the kidneys. Recently, an association has been made between the presence of serum antineutrophil cytoplasmic antibodies (ANCA) and WG. Because WG frequently involves the lung, we sought to evaluate bronchoalveolar lavage (BAL) fluids obtained from 14 patients with WG for the presence of ANCA. Immunoglobulin (Ig) G ANCA was found in the BAL with the same staining patterns as observed in the serum. Patients with active disease had the highest serum and BAL IgG ANCA titers. IgA or IgM ANCA was not detected in the serum or BAL of these patients. Protein analysis of BAL fluid revealed that patients with active, untreated WG had approximately a fourfold elevation in total protein (41.3 versus 10.5 mg/dl), with a disproportionately greater increase in the ratio of IgG to albumin (BAL IgG index = 1.49, normal = 0.74; p = 0.027). The increase of the IgG index in patients with active WG suggests that local production of IgG ANCA occurs in the lungs.

A prospective analysis of bronchoalveolar lavage (BAL) in 13 patients with Wegener's granulomatosis (WG), 20 disease control subjects with idiopathic pulmonary fibrosis (IPF), and 24 normal control subjects was conducted to (1) evaluate the quality of the alveolar inflammatory response associated with active WG; (2) determine whether antineutrophil cytoplasmic antibody (ANCA) is present in alveolar fluid and produced in the lungs of patients with WG; and (3) determine whether inhaled particles or infectious agents may play an etiologic role in WG. BAL in untreated active WG had a marked increase in neutrophils (mean = 42% of total WBC count), and usually in eosinophils (mean = 4%) compared with that in normal control subjects (1.6% neutrophils, 0% eosinophils), and untreated WG in remission (5.9% neutrophils, 0% eosinophils). Disease control subjects with IPF, a process known to be associated with neutrophilic alveolitis, had an increased population of neutrophils (15.4%) and eosinophils (2.7%) in BAL. Leukocyte remnants, as well as intact leukocytes, could be identified within BAL macrophages in the patients with WG and IPF, and rarely in the normal control subjects. Normal subjects and control patients with IPF were all negative for ANCA in serum, whereas ANCA was found in serum and BAL in all patients with active WG who had generalized disease. Protein analysis of BAL revealed a disproportionate increase in the IgG to albumin ration compared with serum values (IgG index) in patients with active untreated disease. The increase in the IgG index suggests that IgG with ANCA reactivity is produced by pulmonary lymphoid tissue. An infectious agent in BAL was not identified by any of the techniques applied in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: Concerns regarding the long-term toxicity of daily cyclophosphamide (CP) therapy for the systemic vasculitides have led us to evaluate alternative approaches to treatment in an attempt to achieve comparable efficacy with less toxicity. This study sought to determine the efficacy, toxicity, and immunologic effects of glucocorticoids (GC) and intermittent high-dose intravenous CP ("pulse" CP) in the treatment of 14 patients with Wegener's granulomatosis (WG)., Patients and Methods: The diagnosis of active WG was supported by a typical clinical presentation and histopathologic findings of vasculitis, granulomatous inflammation, and tissue necrosis. GC treatment was initially provided on a daily basis and later tapered to an alternate-day schedule if vasculitis remained inactive. Pulse CP treatment was initially administered once a month for 6 months. If after 6 months remission had been attained and GC therapy had been discontinued, then pulse CP treatment was given at less frequent intervals thereafter. Treatment and evaluation were provided for participants as inpatients in a clinical research center (National Institutes of Health)., Results: Thirteen of 14 patients (93%) initially experienced unequivocal improvement with pulse CP therapy, and seven of 14 (50%) achieved remission within 4 months. However, treatment was associated with significant toxicity in two patients and later relapses in nine patients, so that a total of 79% either failed to achieve sustained remission or were unable to continue therapy. Three of 14 (21%) patients have achieved sustained remissions with the pulse CP protocol and one additional patient (who had a limited exacerbation of WG) continues to receive that therapy after 14 to 22 months (mean 17 months)., Conclusions: The use of pulse CP and GC therapy in 14 patients with WG was associated with a high initial response rate. However, failure to respond initially to treatment, to sustain improvement, or to tolerate continued treatment was noted in 79% of patients within a period of 1 to 22 months. These observations indicate that this particular pulse CP protocol does not achieve a high degree of lasting efficacy.

AMP deaminase activity was undetectable by a sensitive spectrophotometric assay in the muscle biopsy of a 37-year-old man with gout and exercise-related cramps and myalgia. Venous ammonia failed to rise after ischemic exercise, but the diagnostic value of this test is uncertain because changes of plasma ammonia after exercise varied greatly in different normal individuals. In the patient, AMP deaminase activity was normal not only in erythrocytes, leukocytes and cultured fibroblasts but also in muscle cultures. Presence of AMP deaminase in muscle cultures was probably due to the expression of a fetal isoenzyme under separate genetic control from adult muscle AMP deaminase.

Although transurethral resection of the prostate provides an effective treatment for obstructive voiding symptoms associated with prostate cancer, there is growing concern about the possible role of transurethral resection in the dissemination of this malignancy. To determine the effect of transurethral resection on the rate of development of distant metastasis, we analyzed a large series of patients (379) treated at our institution with definitive radiotherapy for localized prostate cancer that was diagnosed by either needle biopsy or transurethral prostatic resection. In our series the presence of lymph node metastasis was documented by pelvic lymph node dissection in all patients. An initial univariate analysis suggested that patients diagnosed by transurethral resection had distant metastases significantly more rapidly than patients diagnosed by needle biopsy. However, transurethral resection usually was performed because of the presence of obstructive voiding symptoms and such patients were much more likely to have positive lymph node dissections than patients without obstructive voiding symptoms. A proportional hazards regression analysis showed that nodal status and the degree of obstructive voiding symptoms at diagnosis were independent and powerful predictors of the interval to distant metastases, along with stage and grade. The type of initial biopsy (transurethral prostatic resection versus needle biopsy) had no independent prognostic significance in this analysis. Among patients who had substantial obstructive voiding symptoms there was no significant difference in interval to distant metastases between the transurethral prostatic resection and needle biopsy groups. We conclude that the apparent adverse effect of transurethral prostatic resection results from the poor prognosis of tumors causing obstructive voiding symptoms rather than as a direct result of the resection itself.

A 58 year old man, with systemic lupus erythematosus, developed septic arthritis due to an atypical mycobacterium, M. avium. The patient's course, as well as 46 cases reviewed from the literature, illustrates the insidious nature of atypical mycobacterial infections. Septic arthritis or peri-arthritis was generally not suspected at initial evaluation, leading or at least 40% of patients receiving intra-articular steroids for non-specific reasons. A diagnosis was eventually obtained in 85% of cases by surgical biopsy and culture. In only15% was a diagnosis made by culture of synovial or bursal fluid. The relative in vitro resistance of "atypicals" to antituberculous drugs and the frequent necessity for surgery to make a diagnosis, led to surgery consituting partial or total therapy in 89% of cases. Whether patients were treated with surgery alone, surgery plus antituberculous drugs, or antituberculous drugs alone, clinical improvement generally occured. Because most patients had limited follow-up and because atypical mycobacterial infections often relapse, none of the cases reviewed should be considered "cures", be but rather instances of clinically inactive disease.

Three patients with scleroderma were given intravenous infusions of colchicine (2-4 mg/day) for 3 days. Twenty-four-hour urine collections were assayed for total hydroxyproline (HYPRO), an index of collagen resorption, and for nondialyzable polypeptide HYPRO, an index of collagen synthesis. During the colchicine infusions there was a fall in total urinary HYPRO and a slight increase in the per cent nondialyzalbe HYPRO in each patient. The hydroxylysyl-galactosyl-glucose (HGG) to hydroxylysyl-galactose (HG) ratios were not strikingly different in two samples, with the greastest differences in HYPRO excretion. Our results suggested that total body collagen catabolism had diminished without a concomitant decrease in synthesis. In contrast to provocative reports in the literature, these data do not support the hypothesis that administration of colchicine in doses tolerated in man can either inhibit synthesis of new collagen, increase degradation of mature collagen, or be of use in treatment of fibrotic states.

Forty-nine episodes of septic bursitis in 45 patients were reviewed. Our experience concurs with previous studies: (1) the most frequently involved sites were the olecranon (63%) and prepatellar (27%) bursae; (2) Staphylococcus aureus was the commonest pathogen (78%); (3) skin breakage, trauma and/or occupational risk factors were significantly associated with infections (74 and 92% of olecranon and prepatellar episodes, respectively); (4) bursal fluid white blood cell (WBC) counts varied widely (350-392,500 WBC/mm3); and (5) a significant number of patients failed to respond to initial oral antibiotics. In addition to these points, we have been impressed with several clinical observations that merit special emphasis: (1) cellulitis adjacent to the affected bursae was frequent (89%) and often extensive; (2) profound edema occurred in 11% of affected limbs; (3) clinical resolution was slow, occurring at a mean of greater than 5 weeks, but at times requiring as long as 20 weeks to return to baseline status.

Hypoparathyroidism has not been reported in progressive systemic sclerosis (PSS). We describe a patient with PSS and polymyositis with clinical hypoparathyroidism in whom fibrosis of the parathyroid glands was found at autopsy. Normal parathyroid gland architecture includes a collagenous stroma which may fibrose due to the same etiologic factors that are responsible for fibrosis in other organs in PSS. Parathyroid involvement in PSS is probably more common than is currently appreciated.

Twenty-seven adult patients with dermatomyositis or polymyositis were retrospectively evaluated over a mean of four and a half years. Eighty-five percent (23) met the suggested criteria of Bohan and Peter (New England Journal of Medicine, 1975) for definite or probable disease, while 15 percent had possible disease. Upper and lower limb girdle strength was given a value (0 to 5) and averaged. Initially, 26 percent were severely weak and 59 percent moderately weak. All patients were treated with steroids. Within three months, 64 percent had little to no weakness and no patients were severely impaired. These proportions remained relatively constant throughout the study. Eight less severely ill patients received alternate-day prednisone. Only two still require treatment; the remainder have been in remission for a mean period of 19 months. Of 19 who received daily prednisone, five also required cytotoxic drugs and 11 still require treatment. A comparison of the results of this study with those of major urban referral centers reveals that the patients in this study constituted a generally less ill population with a better prognosis. Forty-one percent (11) of patients were able to discontinue all forms of therapy and remain in remission. Thirty percent (eight) achieved remission with only alternate-day steroid therapy, an approach that has been discouraged in the past. Two patients (7 percent) had overt malignancies within one year before to three years after diagnosis of myositis. However, in no instance did a search for occult malignancy give positive results. Cancer detection was accomplished by following clues from history and physical examinations. It is questioned whether extensive evaluations for occult malignancies in patients with idiopathic myositis are cost-effective.

To evaluate the prognostic significance of post-irradiation biopsy results in patients with prostatic cancer, we reviewed the records of 803 patients who had been treated with pelvic lymph node dissection, radioactive gold seed implantation and external beam irradiation. Of the patients 124 had 1 or more biopsies within 6 to 36 months after completion of radiotherapy when there was no evidence of local or distant recurrence of tumor. Patients were followed for a mean of 64 months (range 14 to 175 months) and received no other therapy before relapse. Over-all, 43 of these patients (35 per cent) had a positive biopsy result. The incidence of positive biopsy results correlated directly with the initial stage of the tumor, ranging from 22 per cent of stage B1N to 50 per cent of stage C1 lesions. However, biopsy results did not correlate with the grade of the tumor. Local recurrence and distant metastases were much more common among patients with a positive biopsy result (p equals 0.0006). Local recurrence developed in 58 per cent of the patients with a positive biopsy by 5 years and in 82 per cent by 10 years. Of those in whom all biopsies were negative only 18 per cent had local recurrence by 5 years and 32 per cent by 10 years. Biopsy results retained their prognostic significance even among the more favorable subset of patients whose pelvic lymph nodes were negative initially and those with a normal prostatic examination at biopsy. These results indicate that a post-irradiation prostate biopsy 6 to 36 months after completion of treatment can be used to determine the efficacy of a particular radiotherapeutic regimen as well as the success or failure of radiotherapy in an individual patient.

Eighty-three percent of 24 pregnancies in patients with systemic lupus erythematosus studied retrospectively terminated in normal children. Fifty-four percent of patients had clinical and serological disease exacerbations during pregnancy or in the post-partum period, as contrasted with 4% in the 6 months prior to pregnancy. The presence of significant renal disease and SLE activity in the 6 months prior to pregnancy correlated with exacerbations. A distinction between pre-eclamptic toxemia and lupus exacerbation had to be made in 25% of our patients. There were 2 maternal deaths associated with uncontrolled lupus activity. No potentially viable infants died for reasons directly related to lupus activity.

Episodic digital ischemia may be an isolated abnormality, a symptom of systemic illness or the result of trauma, pharmacologic toxicity, atherosclerosis or Buerger's disease. A complete history and physical examination often provide adequate information for diagnosis. Laboratory evaluation usually confirms the presence of a systemic process, such as one of the rheumatologic disorders or a monoclonal gammopathy. Approaches to therapy differ, depending on the underlying process. In Raynaud's vasospasm, the results of pharmacologic therapy and/or sympathectomy are disappointing; avoidance of smoking and conservation of body heat are essential.

Tendinitis is thought to arise from acute or chronic excessive use of a particular muscle group. Age-related changes at osseotendinous junctions may explain why tendinitis occurs most often after age 50. Bursitis often develops secondary to tendinitis. Local steroid injections are frequently palliative.

Five years following jejunoileal intestinal bypass surgery for obesity, a patient developed debilitating weakness and muscle pain. Osteomalacia was suspected clinically by radiographic and laboratory abnormalities and confirmed by bone biopsy. Malabsorption was documented as well as secondary hyperparathyroidism. Successful treatment of this syndrome with vitamin D and calcium identified a medically reversible disorder which obviated the need for surgical reanastomosis.

Back pain has been estimated to affect about two thirds of the adult population. In most instances the pain is brief and self-limited, but at other times it may be chronic. Although the cause of discomfort may be apparent at times, in many extensively evaluated cases it is not. Chronic arachnoiditis is infrequently considered in the differential diagnosis of back pain. A literature review of arachnoiditis includes only anecdotal cases and series, emphasizing the most severe clinical findings. It is suggested that arachnoiditis may have a place in the differential diagnosis of chronic back pain.

From the extensive morphological studies performed, otosclerosis appears to be ubiquitous, and in many instances subclinical. Despite reports of the efficacy of fluoride for this condition, at present its use should be regarded as experimental.

We report a 59-year-old woman who developed massive, painless ascites attributed to systemic lupus erythematosus. Extensive investigations, including exploratory laparotomy, failed to demonstrate hepatic, renal, cardiac, infectious, or malignant disease. Therapy with systemic corticosteroids resulted in dramatic disappearance of ascites which has not recurred after 2 years.

We have studied the rat remnant kidney model as a tool to assess the impact of secondary oxalosis on renal failure. Although the plasma of uremic rats demonstrated increased levels of oxalic acid, deposits of oxalate crystals in tissue were not observed. The absence of such deposits in the remnant kidney, as well as other tissues, may be due to a lesser degree of hyperoxalemia observed in the rat compared to man or may reflect that uremic deaths among the experimental animals occurred prior to formation of detectable calcium oxalate deposition. We conclude that the rat remnant kidney is not a suitable model to study the impact of uremic oxalosis in man.

Acute febrile neutrophilic dermatosis was first reported by Sweet in 1964. Sweet demonstrated the value of steroid therapy in these cases. Many authors have since confirmed the efficacy of steroids in treating this usually self-limiting, but often temporarily disabling, process. This case report and review concerns a patient with Sweet's syndrome in whom dramatic relief of severe arthralgias, myalgias, and painful skin lesions occurred using indomethacin. Steroids were not used because of the good response to an empiric trial of indomethacin and the likelihood of concurrent histoplasmosis.