The role of genetic variants in CRP in radiographic severity in African Americans with early and established rheumatoid arthritis.

This study investigates the association of CRP (C-reactive protein) single-nucleotide polymorphisms (SNPs) with plasma CRP levels and radiographic severity in African Americans with early and established rheumatoid arthritis (RA). Using a cross-sectional case-only design, CRP SNPs were genotyped in two independent sets of African Americans with RA: Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR 1) and CLEAR 2. Radiographic data and CRP measurements were available for 294 individuals from CLEAR 1 (median (interquartile range (IQR) 25-75) disease duration of 1 (0.6-1.6) year) and in 407 persons from CLEAR 2 (median (IQR 25-75) disease duration of 8.9 (3.5-17.7) years). In CLEAR 1, in adjusted models, the minor allele of rs2808630 was associated with total radiographic score (incident rate ratio 0.37 (95% confidence interval (CI) 0.19-0.74), P-value=0.0051). In CLEAR 2, the minor allele of rs3093062 was associated with increased plasma CRP levels (P-value=0.002). For each rs3093062 minor allele, the plasma CRP increased by 1.51 (95% CI 1.15-1.95) mg dl(-1) when all the other covariates remained constant. These findings have important implications for assessment of the risk of joint damage in African Americans with RA.

Take a walk in the park? A cross-over pilot trial comparing brisk walking in two different environments: park and urban.

OBJECTIVE: The objective of the present study is to investigate whether differences exist between a 30 minute brisk walk taken in two different environments in order to determine which environment best facilitates current physical activity guidelines: park or urban. METHODS: In this randomised cross-over pilot study, participants performed a self-timed 30 minute brisk walk in two different environments, park and urban, in Glasgow, Scotland (October 2009 to January 2010). Cadence, recorded using the activPAL™ activity monitor, was used to measure intensity. Outcome measures were: mean cadence; moderate-to-vigorous physical activity time accumulated in bouts lasting ≥ 10 min; number of walking breaks; and duration. RESULTS: A convenience sample of 40 healthy adults was recruited: 16 males, 24 females, mean age 22.9 (5.5) years. The mean cadence for the whole walk was higher in the park: 119.3 (8.3) vs. 110.9 (8.9) steps/min. Participants accumulated more moderate-to-vigorous physical activity in ≥ 10 minute bouts during park walks: 25.5 (9.6) [median (interquartile range)] vs. 14.0 (20.3) min. There was no difference in self-timed duration between locations. CONCLUSION: Participants accumulated more moderate-to-vigorous physical activity in bouts ≥ 10 min in duration on park walks due to the lack of interruptions in walking. Hence the park environment better facilitated the achievement of current physical activity guidelines. Further research involving a larger, more heterogeneous sample is recommended.

Effect of preoperative oral antibiotics in combination with mechanical bowel preparation on inflammatory response and short-term outcomes following left-sided colonic and rectal resections.

Background: Preoperative oral antibiotics in addition to intravenous antibiotics and mechanical bowel preparation (MBP) may influence the gut microbiome and reduce both the postoperative systemic inflammatory response to surgery and postoperative infective complications following colorectal resection. This propensity score-matched study compared outcomes of patients undergoing left-sided colonic or rectal resection with or without a combination of oral antibiotics and MBP. Methods: The addition of oral antibiotics and MBP to prophylactic intravenous antibiotics in left-sided colonic and rectal resections was introduced in 2015-2016 at a single institution. Propensity score matching was undertaken to compare the effects of oral antibiotics plus MBP versus neither oral antibiotics nor MBP on the postoperative systemic inflammatory response and short-term outcomes in patients undergoing left-sided colonic or rectal resection between 2013 and 2018. Results: Of 396 patients who had propensity score matching for host, anaesthetic and operative factors, 204 matched patients were identified. The addition of oral antibiotics and MBP was associated with a significantly reduced postoperative inflammatory response (reduced postoperative Glasgow Prognostic Score) on day 3 (odds ratio (OR) 0·66, 95 per cent c.i. 0·44 to 0·99; P = 0·013) and day 4 (OR 0·46, 0·30 to 0·71; P = 0·001). Significantly reduced overall complications (OR 0·31, 0·17 to 0·56; P < 0·001), infective complications (OR 0·41, 0·22 to 0·77; P = 0·011), surgical-site infection (OR 0·37, 0·17 to 0·83; P = 0·024) and postoperative length of hospital stay (median 7 days versus 8 days in patients who had intravenous antibiotics alone; P = 0·050) were also observed. Conclusion: Preoperative oral antibiotics and MBP in addition to prophylactic intravenous antibiotics were associated with a reduction in the postoperative systemic inflammatory response and postoperative complications in patients undergoing resectional left-sided colonic or rectal surgery.

Antecedentes: La administración preoperatoria de antibióticos por vía oral (preoperative oral antibiotics, OAB), además de por vía intravenosa y de la preparación mecánica del colon (mechanical bowel preparation, MBP) puede afectar al microbioma intestinal y disminuir tanto la respuesta postoperatoria sistémica inflamatoria a la cirugía, como las complicaciones infecciosas postoperatorias tras una resección colorrectal. Este estudio emparejado por puntaje de propensión comparó los resultados de pacientes sometidos a resección del colon izquierdo o resección rectal con y sin una combinación de OAB y MBP. Métodos: La adición de OAB y MBP a la administración profiláctica de antibióticos por vía intravenosa fue introducida en 2015­2016 en un centro médico. Se llevó a cabo un estudio emparejado por puntaje de propensión para comparar los efectos de OAB con MBP versus la no administración de OAB ni el uso de MBP sobre la respuesta postoperatoria sistémica inflamatoria a la cirugía y los resultados a corto plazo en pacientes sometidos a resección del colon izquierdo o resección rectal desde el 2013 al 2018. Resultados: De los 396 pacientes incluidos en el emparejamiento por puntaje de propensión relativo a factores relacionados con el huésped, anestésicos y operatorios, se identificaron 204 pacientes emparejados. La adición de OAB y MBP se asoció con una disminución significativa de la respuesta inflamatoria postoperatoria (disminución postoperatoria de la puntuación pronóstica de Glasgow el día 3 (razón de oportunidades, odds ratio, OR 0,66, i.c. del 95% 0,44­0,99, P = 0,013) y el día 4 (OR 0,46, i.c. del 95% 0,30­0,71, P = 0,001). También se observaron reducciones significativas de las complicaciones globales (OR 0,31, i.c. del 95% 0,17­0,56, P < 0,001), complicaciones infecciosas (OR 0,41, i.c. del 95% 0,17­0,83, P = 0,011), infecciones del sitio quirúrgico (OR 0,37, i.c. del 95% 0,17­0,83, P = 0,024) y duración de la estancia hospitalaria postoperatoria (mediana 8 versus 7 días, P = 0,05). Conclusión: La adición preoperatoria de OAB y MBP a la administración profiláctica de antibióticos intravenosos se han asociado con una disminución de la respuesta inflamatoria sistémica postoperatoria y de las complicaciones postoperatorias en pacientes sometidos a resección del colon izquierdo o cirugía rectal.

Cigarette smoking, disease severity and autoantibody expression in African Americans with recent-onset rheumatoid arthritis.

OBJECTIVE: To examine the association of smoking with clinical and serological features in African Americans with recent-onset rheumatoid arthritis (RA) and to explore whether this association is dependent on the presence of the HLA-DRB1 shared epitope (SE). METHODS: In African Americans with recent-onset RA (n = 300), we examined the association of cigarette smoking (current versus past versus never and pack-years of exposure) with anti-cyclic citrullinated peptide antibody, rheumatoid factor (RF) (IgM and IgA), rheumatoid nodules and baseline radiographic erosions using logistic and cumulative logistic regression (adjusting for SE status). We also examined for evidence of interaction between smoking status and SE for all outcomes. RESULTS: Although there was no association with RF-IgA seropositivity, current smokers were approximately twice as likely as never smokers to have higher IgA-RF concentrations (based on tertiles; OR = 1.74; 95% CI 1.05 to 2.88) and nodules (OR = 2.43; 95% CI 1.13 to 5.22). These associations were most pronounced in those with more than 20 pack-years of exposure. There was no association of smoking status or cumulative tobacco exposure with anti-cyclic citrullinated peptide antibody, IgM-RF or radiographic erosions. There was also no evidence of a biological or statistical SE-smoking interaction for any of the outcomes examined. CONCLUSIONS: This is the first study to systematically examine the association of cigarette smoking with RA-related features in African Americans. Cigarette smoking is associated with both subcutaneous nodules and higher serum concentrations of IgA-RF in African Americans with RA, associations that may have important implications for long-term outcomes in this population.

Molecular markers and sentinel organisms for environmental monitoring.

Molecular methods are useful for both to monitor anthropogenic viral, bacterial, and protozoan enteropathogens, and to track pathogen specific markers in a complex environment in order to reveal sources of these pathogens. Molecular genetic markers for fecal viruses, bacteria, and protozoans hold promise for monitoring environmental pollution and water quality. The demand for microbiologically safe waters grows exponentially due to the global demographic rise of the human population. Economically important shellfish, such as oysters, which are harvested commercially and preferentially consumed raw can be of public health importance if contaminated with human waterborne pathogens. However, feral molluscan shellfish which do not have an apparent economic value serve as indicators in monitoring aquatic environments for pollution with human waterborne pathogens and for sanitary assessment of water quality. Current technology allows for multiplexed species-specific identification, genotyping, enumeration, viability assessment, and source-tracking of human enteropathogens which considerably enhances the pathogen source-tracking efforts.

Parenteral gold therapy in the Felty syndrome. Experience with 20 patients.

Most of the patients with the Felty syndrome suffer from such complications as fevers, infections, cutaneous ulcers, and vasculitis. Unfortunately, there are no therapeutic interventions that are predictably beneficial. We report our experience with 20 patients who received parenteral gold therapy for 2 to 114 months (mean, 23.6 months). All had complications of the Felty syndrome. On parenteral gold therapy, 60% had a complete response, 20% had a partial response, and 20% were unresponsive by preselected criteria. No serious complications were encountered. We think that parenteral gold therapy should be considered early, before other agents, in the treatment of this condition.

Rheumatoid vasculitis: survival and associated risk factors.

We describe the clinical and laboratory characteristics of 52 patients with rheumatoid vasculitis whose condition was diagnosed at a tertiary care center between 1974 and 1981, and we report their survival and the factors that were associated with decreased survival. The patients with rheumatoid vasculitis had decreased survival in comparison with an age-, sex-, and region-matched general population. Their survival was also decreased in comparison to that of an incidence cohort of community patients with rheumatoid arthritis. In the latter cohort, decreased survival was confined to those patients with classic but not definite rheumatoid arthritis. After partial correction for referral bias, we found no difference in survival between the cohort with rheumatoid vasculitis and the cohort with classic rheumatoid arthritis. We found that the age at diagnosis of rheumatoid vasculitis, the therapeutic decisions before and at diagnosis, and the referral distance were the best predictors of survival. Abnormal urinary sediment and hypergammaglobulinemia also predicted poor survival, but because of a lack of specificity in a small number of clinically abnormal values, we urge a cautious interpretation of their importance.

Peripheral neuropathy in primary Sjögren's syndrome.

Sjögren's syndrome (dryness of eyes, mouth, and other mucous membranes) may be associated with disease of joints, blood, internal organs, skin, and central and peripheral nervous systems. We reviewed 33 cases of primary Sjögren's syndrome and peripheral neuropathy evaluated by neurologic examinations and EMG at the Mayo Clinic from 1976 to 1988, and studied sural nerve biopsy specimens in 11 of them. Symmetric sensorimotor polyneuropathy occurred most frequently, followed by symmetric sensory neuropathy. Autonomic neuropathy, mononeuropathy, or cranial neuropathy (especially trigeminal neuropathy) was superimposed on generalized neuropathy in approximately one-fourth of patients. The course generally was slowly progressive, except for a few patients who may have improved with prednisone therapy. Although spinal ganglion involvement might have accounted for some of the clinical and neurophysiologic findings, we found evidence that necrotizing vasculitis was involved in fiber degeneration. All nerve biopsies revealed perivascular inflammatory infiltrates and other vessel abnormalities, which were diagnostic in two cases and strongly suggestive of necrotizing vasculitis in six cases. Axonal degeneration predominated over demyelination and sometimes was focal or multifocal. In neuropathy of unknown cause, particularly if it is sensory, autonomic, or involves trigeminal nerve, consider Sjögren's syndrome.

Spiritual healing as a therapy for chronic pain: a randomized, clinical trial.

Spiritual healing is a popular complementary and alternative therapy; in the UK almost 13000 members are registered in nine separate healing organisations. The present randomized clinical trial was designed to investigate the efficacy of healing in the treatment of chronic pain. One hundred and twenty patients suffering from chronic pain, predominantly of neuropathic and nociceptive origin resistant to conventional treatments, were recruited from a Pain Management Clinic. The trial had two parts: face-to-face healing or simulated face-to-face healing for 30 min per week for 8 weeks (part I); and distant healing or no healing for 30 min per week for 8 weeks (part II). The McGill Pain Questionnaire was pre-defined as the primary outcome measure, and sample size was calculated to detect a difference of 8 units on the total pain rating index of this instrument after 8 weeks of healing. VASs for pain, SF36, HAD scale, MYMOP and patient subjective experiences at week 8 were employed as secondary outcome measures. Data from all patients who reached the pre-defined mid-point of 4 weeks (50 subjects in part I and 55 subjects in part II) were included in the analysis. Two baseline measurements of outcome measures were made, 3 weeks apart, and no significant differences were observed between them. After eight sessions there were significant decreases from baseline in McGill Pain Questionnaire total pain rating index score for both groups in part I and for the control group in part II. However, there were no statistically significant differences between healing and control groups in either part. In part I the primary outcome measure decreased from 32.8 (95% CI 28.5-37.0) to 23.3 (16.8-29.7) in the healing group and from 33.1 (27.2-38.9) to 26.1 (19.3-32.9) in the simulated healing group. In part II it changed from 29.6 (24.8-34.4) to 24.0 (18.7-29.4) in the distant healing group and from 31.0 (25.8-36.2) to 21.0 (15.7-26.2) in the no healing group. Subjects in healing groups in both parts I and II reported significantly more 'unusual experiences' during the sessions, but the clinical relevance of this is unclear. It was concluded that a specific effect of face-to-face or distant healing on chronic pain could not be demonstrated over eight treatment sessions in these patients.

Antiinflammatory activity of a series of substituted 2,3-dihydro-6-hydroxypyrimido[2,1-f]purine-4,8(1H,9H)-diones.

A series of substituted analogues based on the novel 2,3-dihydro-6-hydroxypyrimido[2,1-f]purine-4,8(1H,9H)-dione ring system have been synthesized and shown to exhibit antiinflammatory activity in the adjuvant-induced arthritis rat model (AAR). The activity exhibited by the pyrimidopurinediones in this model of chronic inflammation is comparable to that of their previously studied 2-oxo congeners, the 6-hydroxypyrimido[2,1-f]purine-2,4,8-(1H,3H,9H)-triones, the best of which show potency levels approximately equal to that of naproxen. On the basis of its potency in the AAR assay, 9-benzyl-2,3-dihydro-1,3-dimethyl-6-hydroxy-7-(3-methyl-2-butenyl) pyrimido-[2,1-f]purine-4,8(1H,9H)-dione was selected for further evaluation and found to exhibit cyclooxygenase inhibitory activity in the in vitro rat neutrophil model. With respect to side-effect liability, this prenylated derivative has been shown to be devoid of gastric ulcer inducing potential, as well as the ocular toxicity observed previously with the 2-oxo series.

Antiulcer agents. 4. Conformational considerations and the antiulcer activity of substituted imidazo[1,2-a]pyridines and related analogues.

Definition of the interrelationship between the conformational characteristics of a series of substituted imidazo[1,2-a]pyridines and their antiulcer activity was investigated by examining the conformational properties of 3-cyano-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine (1), using a variety of experimental and theoretical methods. The results of these studies was the identification of two distinctly different candidates, designated the "folded" and the "extended" conformation, respectively, to represent the two possible minimum-energy conformations of 1. In order to select the biologically relevant conformer, a group of 3-substituted 2-methylimidazo[1,2-a]pyridines, having either a cis or a trans 2-phenylethenyl substituent at the 8-position were designed as conceptually simple and synthetically accessible semirigid analogues of the respective candidate conformers. Gastric antisecretory activity was found to reside only in the trans isomers (compounds 11, 15, and 17), which mimic the "extended" conformation. This observation led to the construction of 8,9-dihydro-2-methyl-9-phenyl-7H-imidazo[1,2-a]pyrano[2,3-c]pyridi ne-3- acetonitrile (40), a rigid tricyclic analogue that is effectively locked in the "extended" conformation and that exhibited an antiulcer profile comparable to that of prototype 1. These results unequivocally demonstrate that, in accord with expectation for a drug operating at a specific receptor, the conformational characteristics of the molecule have a substantial effect in determining its antiulcer activity. More precisely, it has been demonstrated that it is the "extended" conformation of 1 that represents the "bioactive" form of the drug. These results constitute the basis for a molecular probe that should aid in the investigation of the as yet uncharacterized gastric proton pump enzyme (H+/K+-ATPase), by means of which 1 and its analogues presumably exert their pharmacologic actions.

Antiulcer agents. 1. Gastric antisecretory and cytoprotective properties of substituted imidazo[1,2-a]pyridines.

A novel class of antiulcer agents, the substituted imidazo[1,2-a]pyridines, is described. The present compounds are not histamine (H2) receptor antagonists nor are they prostaglandin analogues, yet they exhibit both gastric antisecretory and cytoprotective properties. The mechanism of gastric antisecretory activity may involve inhibition of the H+/K+-ATPase enzyme. Structure-activity studies led to the identification of 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, SCH 28080 (27), which was selected for further development and clinical evaluation.

Antiinflammatory activity of substituted 6-hydroxypyrimido[2,1-f]purine-2,4,8(1H,3H,9H)-triones. Atypical nonsteroidal antiinflammatory agents.

A novel class of antiinflammatory drugs, which are substituted derivatives of the fused tricyclic system 6-hydroxypyrimido[2,1-f]purine-2,4,8(1H,3H,9H)-trione, is described. Synthetic procedures and structure determination with the assistance of X-ray crystallography are discussed. Semiempirical molecular orbital calculations are used to investigate the relative stability of the possible isomers and tautomers of the title compounds. A biological profile of the class, and of several of the more potent analogues, in several antiinflammatory models, including the adjuvant-induced arthritis and the collagen II models, is defined. Several members of the class are shown to possess extremely low ulcerogenic effects in spite of exhibiting cyclooxygenase inhibition. A preliminary bioavailability study of two of the lead structures is presented. The compounds 6-72 appear to constitute a class of drugs that shows interesting potential antiarthritic activity and also exhibits an activity profile different from that of the standard classical NSAI drugs, as determined by a comparison of the profile of this class of drug with that of several standard agents. Certain findings from toxicological studies have precluded the further development of compounds within this group, although related structural types are being investigated.

Antiulcer agents. 2. Gastric antisecretory, cytoprotective, and metabolic properties of substituted imidazo[1,2-a]pyridines and analogues.

The search for a successor to 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, Sch 28080 (27), a compound that exhibits gastric antisecretory and cytoprotective properties and has undergone clinical evaluation as an antiulcer agent, has culminated in the identification of four related compounds that exhibit pharmacologic profiles similar to that of 27. In three of these potential successors an amino group functions as a surrogate for the 3-cyanomethyl substituent of the prototype. The present work concerns, in addition to an evaluation of the structure-activity relationships of a series of analogues of 27, preliminary studies of the pharmacodynamics and metabolism of 27, performed with the aid of cyano carbon labeled versions of the drug (13C labeled; 28; 14C labeled, 29). These studies have shown that 27 is well-absorbed and extensively metabolized and that the major metabolite of 27 is the thiocyanate anion. A similar study performed on 3-amino-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, labeled at the 3-position with carbon-13 (41) or carbon-14 (42), revealed that this compound, which has an antisecretory/cytoprotective profile comparable to that of 27, is also metabolized to thiocyanate anion, although this must occur via a different mechanism. The chemistry section includes a discussion of the potential sites of protonation of the pharmacologically similar 3-amino analogue 40 and the structurally related imidazo[1,2-a]pyrazine 67. Predictions based on charge density and protonation product stabilities are presented. That N1 is the site of protonation in these analogues has been definitively demonstrated by X-ray crystal structure analysis, which also unequivocally established the assigned imidazo[1,2-a]pyrazine ring structure.

Update on systemic necrotizing vasculitis.

The systemic necrotizing vasculitides are classified into vasculitic syndromes on the basis of the pattern of clinical and pathologic involvement. The vasculitides have certain common clinical and laboratory abnormalities. Systemic necrotizing vasculitis is diagnosed on the basis of clinical features, and the vascular nature of the disease is determined by biopsy of involved tissue or angiography. The outcome is dependent on the extent of visceral involvement. Vascular inflammation influences the physiologic features of the vessel and may trigger vasoconstriction. Although glucocorticoids combat the inflammation, they may augment vasoconstriction and platelet aggregation. These effects must be considered in designing a management approach and in evaluating the cause and management of ischemic complications.

Series on pharmacology in practice. 9. Glucocorticoids in rheumatic disease.

Glucocorticoids are potent anti-inflammatory agents that play an important role in the therapy of many patients with connective tissue diseases, including systemic lupus erythematosus, polymyalgia rheumatica, various types of vasculitis, and complications of rheumatoid arthritis. Glucocorticoids reduce the number and influence the function of lymphocytes, monocytes, and eosinophils in peripheral blood. Prolonged high doses of glucocorticoids result in decreased levels of immunoglobulins, particularly IgG. Granulocytes are increased in the peripheral blood, but their migration to sites of inflammation is diminished. Glucocorticoids inhibit release of lysosomal enzymes. Although they have no effect on the factor or factors that initiate inflammation, glucocorticoids have proved to be effective in the treatment of inflammatory manifestations of disease. Among significant adverse effects of glucocorticoid therapy are osteoporosis, aseptic necrosis of bone, and steroid myopathy.

Lymphoid neoplasia following connective tissue disease.

A retrospective review was undertaken to ascertain whether there are distinctive histopathologic features of the lymphoid neoplasms that occur in patients with previous connective tissue disease. Of 29 patients studied, 12 had malignant lymphoma with diffuse large-cell cytomorphology. Only 1 of these 12 had an immunoblastic cell type. The remaining 17 patients had neoplasia of a widely diverse nature. Six had lymphocytic lymphoma (one nodular poorly differentiated, three diffuse poorly differentiated, and three diffuse well differentiated), two had Hodgkin's disease, three had plasma cell myeloma, and six had chronic lymphocytic leukemia. Data fail to confirm a relationship between lymphoid proliferations with immunoblastic morphology and connective tissue diseases.

Clinical features, prognosis, and response to treatment in polyarteritis.

Fifty-three patients with polyarteritis who were followed up for at least 2 years were defined clinically and studied retrospectively to determine the influence of clinical factors and treatment on the prognosis. There was a spectrum of severity of disease, and the 5-year survival in the group was 55%. A small number of patients had evidence of ongoing immune-complex disease, as indicated by the presence of cryoglobulins or hepatitis Bs antigen or by diminished serum complement. These markers were not associated with distinct clinical features and did not influence prognosis. Organ involvement that most adversely affected prognosis was that of the gut and the kidneys. Six of 8 patients with bowel infarction or serious gastrointestinal bleeding died, and 6 of 10 patients with renal insufficiency died. Hypertension and peripheral neuropathy did not influence the prognosis. Thirty-six patients were treated with corticosteroids alone and 14 with a combination of corticosteroids and cytotoxic agents (3 received no treatment); the outcome was the same in both groups. Twenty-two in the steroid-alone group and six in the combination group were alive when last seen. Early deaths were usually due to complications directly related to the vasculitis, and late deaths were often due to cerebrovascular or cardiovascular complications. At the last follow-up, 18 patients were in remission, and 13 had inactive vasculitic disease and were on maintenance treatment.

Skin fibrinolytic activity in cutaneous and systemic vasculitis.

Study of involved and uninvolved skin from patients with necrotizing vasculitis revealed diminished tissue fibrinolytic activity deposition of immunoreactants in involved skin. In these patients, the depletion of tissue fibrinolytic activity is probably the result of vessel injury secondary to the local deposit of immunoreactants. In addition, there was diminished tissue fibrinolytic activity in uninvolved skin from patients with and without clinical skin involvement, unassociated with the deposition of immunoreactants. The precise mechanism for diminished tissue lytic activity in these latter patients is not known, but it may be associated with generalized activation of the coagulation and fibrinolytic mechanisms that result in local depletion of tissue fibrinolytic activity. These local changes may aggravate the clinical course of the disease as well as inhibit the healing of the lesions.

Immunologic mechanisms in systemic vasculitis.

Thirty-four patients with systemic vasculitis were studied to determine the possible type and frequency of associated immunologic abnormalities. The patients were divided into three clinical groups--those with systemic vasculitis without respiratory tract involvement, those with systemic vasculitis with respiratory tract involvement (particularly Churg-Strauss vasculitis and Wegener's granulomatosis), and those with limited vasculitis without visceral involvement. A diminished level of serum complement was found in half the patients with systemic vasculitis without respiratory tract involvement. These patients usually had diffuse skin disease that often was associated with the presence of rheumatoid factor and cryoglobulinemia and most likely represented an immune-complex induced disease. The serum IgE often was elevated in patients who had systemic vasculitis with respiratory tract involvement, particularly those with Churg-Strauss vasculitis and Wegener's granulomatosis, and may be a clue to the pathogenesis in this group of patients.