The accuracy of physical examination to detect abdominal aortic aneurysm.

BACKGROUND: Abdominal palpation during physical examination is an important means of detecting abdominal aortic aneurysm (AAA), but limited information is available on its accuracy. METHODS: Two hundred subjects (aged 51-88 years), 99 with and 101 without AAA as determined by previous ultrasound, each underwent physical examination of the abdomen by 2 internists who were blinded to each other's findings and to the ultrasound diagnosis. RESULTS: The overall accuracy of abdominal palpation for detecting AAA was as follows: sensitivity, 68% (95% confidence interval [CI], 60%-76%); specificity, 75% (95% CI, 68%-82%); positive likelihood ratio, 2.7 (95% CI, 2.0-3.6); negative likelihood ratio 0.43 (95% CI, 0.33-0.56). Interobserver pair agreement for AAA vs no AAA between the first and second examinations was 77% (kappa = 0.53). Sensitivity increased with AAA diameter, from 61% for AAAs of 3.0 to 3.9 cm, to 69% for AAAs of 4.0 to 4.9 cm, 72% for AAAs of 4.0 cm or larger, and 82% for AAAs of 5.0 cm or larger. Sensitivity in subjects with an abdominal girth less than 100 cm (40-in waistline) was 91% vs 53% for girth of 100 cm or greater (P<.001). When girth was 100 cm or greater and the aorta was palpable, sensitivity was 82%. When girth was less than 100 cm and the AAA was 5.0 cm or larger, sensitivity was 100% (12 examinations). Factors independently associated with correct examination findings included AAA diameter (odds ratio [OR], 1.95 per centimeter increase; 95% CI, 1.06-3.58); abdominal girth (OR, 0.90 per centimeter increase; 95% CI, 0.87-0.94); and the examiner's assessment that the abdomen was not tight (OR, 2.68; 95% CI, 1.17-6.13). CONCLUSIONS: Abdominal palpation has only moderate overall sensitivity for detecting AAA, but appears to be highly sensitive for diagnosis of AAAs large enough to warrant elective intervention in patients who do not have a large girth. Abdominal palpation has good sensitivity even in patients with a large girth if the aorta is palpable.

A diagnostic algorithm for distinguishing the eosinophilia-myalgia syndrome from fibromyalgia and chronic myofascial pain.

OBJECTIVE: To develop a diagnostic algorithm for the eosinophilia-myalgia syndrome (EMS) that complements the existing case definition. METHODS: We conducted a retrospective study using data on 59 clinical and laboratory variables from a consecutive referral cohort of 91 patients with EMS meeting the Centers for Disease Control and Prevention case definition. Age and sex matched controls included 93 patients with fibromyalgia and 99 patients with chronic myofascial pain. The study period was March 1989 to April 1992. Recursive partitioning was used to create a diagnostic algorithm. RESULTS: In the 283 case patients and controls with disabling myalgias, 4 differentiating variables identified patients with EMS: extremity edema, leukocyte count > 12.5 x 10(9)/l, dyspnea, and absence of arthralgias. These 4 variables form a diagnostic algorithm that has a sensitivity of 95.6%, a specificity of 96.9%, and positive and negative predictive values of 93.5 and 97.9%, respectively. CONCLUSION: This algorithm is practical and can be easily applied in any medical setting. It also readily distinguishes EMS from other common myalgia syndromes.

Thoracic aortic aneurysm and rupture in giant cell arteritis. A descriptive study of 41 cases.

OBJECTIVE: To determine the features and outcomes of patients with giant cell arteritis (GCA) who have aneurysms or rupture of the thoracic aorta. METHODS: Patients with GCA seen over a 40-year period who had aneurysms and/or rupture of the thoracic aorta were identified by assistance of a computerized indexing system. The presence of thoracic aortic aneurysms (TAA), with or without aortic valve insufficiency (AI), was determined by radiographs, computed tomography scans, and ultrasound studies of the thorax, angiograms of the aorta, and postmortem examination. RESULTS: Ten men and 31 women with GCA were found to have TAA and/or rupture. Three developed TAA before GCA was diagnosed, 5 developed aortic findings near the time of the diagnosis, and 33 after the diagnosis of GCA (median of 7 years after diagnosis). Sixteen patients developed acute aortic dissection, which caused death in 8. Nineteen patients also had AI due to aortic root dilation, 15 of whom developed congestive heart failure. Eighteen patients underwent 21 surgical procedures for TAA resection and/or aortic valve replacement or repair. Aortitis was documented histologically in 10 cases. CONCLUSION: Thoracic aortic complications in GCA are associated with serious outcomes that have been underrecognized and may be fatal. Physicians should be alert to the development of these complications at any time in the course of GCA, even many years after usual symptoms have subsided.

The treatable dementia of Sjögren's syndrome.

Progressive dementia developed during a 15-month period in a 56-year-old woman with serologically and clinically documented primary Sjögren's syndrome. Findings from magnetic resonance imaging and angiography were normal, but a brain biopsy disclosed perivascular lymphocytic inflammation in leptomeningeal and parenchymal vessels. Treatment with high-dose corticosteroids produced rapid and nearly complete resolution of the dementia.

Eosinophilia myalgia syndrome: I. Immunocytochemical evidence for a T-cell-mediated immune effector response.

Specimens of muscle and fascia from 13 patients fulfilling the Centers for Disease Control criteria for the eosinophilia myalgia syndrome (EMS) were studied by quantitative immunocytochemical analysis. The immunolocalization of CD3, CD4, CD8, CD22, and CD56 markers, the gamma delta T-cell receptor, major histocompatibility complex (MHC) class I complex and class II antigens, and complement membrane attack complex (MAC) were examined. The distribution and relative proportions of T cells and T-cell subsets, B cells, macrophages, and eosinophils were determined at perivascular, perimysial, endomysial, and fascial sites of accumulation. At all sites, T cells were predominant, CD8+ cells outnumbered CD4+ cells 6- to 20-fold, and between 60 and 80% of T cells were activated. B cells and eosinophils each accounted for less than 3% of inflammatory cells. Very few cells expressed either the gamma delta T-cell receptor or natural killer cell markers. As in dermatomyositis (DM), MHC class I antigen complex expression was increased on many structurally normal muscle fibers, but in contrast to DM, microvascular MAC deposits were not a feature of EMS. The findings implicate a cellular immune response directed against a connective tissue component in EMS.

Migration of dog polymorphonuclear neutrophilic leukocytes to formylated peptides.

Formylated peptides are potent stimulants of polymorphonuclear neutrophilic leukocyte (PMN) migration from species such as humans and rabbits. Interestingly, PMNs from dogs, cats, pigs and cows have been reported as refractory to N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) and generally are believed not to express formylpeptide receptors. Formylpeptides are a major component of conditioned media from E. coli cultures and believed to be a significant element in inflammatory responses elicited by E. coli. Our studies have found that E. coli filtrate was a potent stimulant of dog PMN migration. Inhibition of migration to E. coli filtrates by the antagonist t-botyloxycarbonyl-l-methionyl-l-leucyl-l-phenylalanine (t-boc-MLP) demonstrated that the migration was mediated through the formylated peptide receptor. Migration in response to peptides with higher affinity for the formylpeptide receptor than FMLP was further evidence for these receptors on the dog PMN. PMNs from dogs migrated in response to FMLP at high concentrations (100 microM); however, pretreatment with phorbol myristate acetate resulted in increased migration of dog PMNs in response to concentrations of FMLP as low as 1 pM. These results demonstrate that dog PMNs are responsive to formylpeptides and that these responses can be up-regulated by PMA. Thus PMNs from a species previously thought incapable of responding to formylpeptides can respond to formylpeptide analogs with high affinity for the receptor as well as be primed for enhanced migration to FMLP by PMA.

The clinical spectrum of the eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Clinical features in 20 patients and aspects of pathophysiology.

We describe the clinical spectrum of the L-tryptophan-associated eosinophilia-myalgia syndrome in 20 patients. In all but one case, patients met the Centers for Disease Control (CDC) case definition for the syndrome: peripheral blood eosinophilia (eosinophil count greater than 1.0 x 10(9)/L) and generalized, disabling myalgias without other recognized causes. Three patients with eosinophilia and myalgia developed eosinophilic fasciitis, and 4 other patients developed, respectively, pneumonitis and myocarditis, neuropathy culminating in respiratory failure, encephalopathy, and fibrosis about the common bile duct. No relation was apparent between dose or duration of L-tryptophan exposure and the eosinophilia-myalgia syndrome. No organic contaminants were identified in L-tryptophan preparations taken by patients or asymptomatic users when these preparations were examined by chromatography or mass spectroscopy. Biopsy specimens in 12 patients showed a mononuclear exudate with a variable admixture of eosinophils in affected tissues, including skin, fascia, muscle, and some viscera. Eosinophil toxic granule proteins, major basic protein, and eosinophil-derived neurotoxin were elevated in the serum and urine of patients compared with normal control subjects (P less than 0.01 and P less than 0.02, respectively). Immunofluorescence showed major basic protein deposited outside of eosinophils in affected tissues, indicating that toxic granule proteins are released in diseased organs. Treatment included withdrawal of L-tryptophan in all cases. Corticosteroids were prescribed for 16 patients and diuretics alone for 1 patient; no drugs were prescribed for 3 patients. Four patients have recovered fully, others are stable or slowly recovering, and 1 is gravely ill despite prolonged treatment.

Vasculopathy associated with the antiphospholipid antibody syndrome.

Antiphospholipid antibodies including the false-positive serologic test for syphilis, the lupus circulating anticoagulant, and the anticardiolipin antibody can be associated with recurrent thrombotic events, recurrent fetal loss, and thrombocytopenia. A range of other possible clinical associations also exists, including neurologic events, skin lesions, and cardiac lesions. The pathology of these lesions and the pathophysiology are discussed. Treatment is controversial but when indicated is directed toward prevention of recurrent episodes using anticoagulants including antiplatelet agents, warfarin, and heparin as well as occasionally prednisone with or without immunosuppressive agents.

Chronic stress, leukocyte subpopulations, and humoral response to latent viruses.

Psychological stress has been shown to affect immune system status and function, but most studies of this relationship have focused on acute stress and/or laboratory situations. The present study compared total numbers of leukocytes and lymphocyte subpopulations (determined by flow cytometry) and antibody titers to latent and nonlatent viruses among a group of chronically stressed individuals living near the damaged Three Mile Island (TMI) nuclear power plant with those of a demographically comparable control group. Urinary catecholamine and cortisol levels were also examined. Residents of the TMI area exhibited greater numbers of neutrophils, which were positively correlated with epinephrine levels. The TMI group also exhibited fewer B lymphocytes, T-suppressor/cytotoxic lymphocytes, and natural killer cells. Antibody titers to herpes simplex were significantly different across groups as well, whereas titers to nonlatent rubella virus as well as IgG and IgM levels were comparable.

Scleromyxedema: a scleroderma-like disorder with systemic manifestations.

Scleromyxedema is a rare fibromucinous connective tissue disorder characterized by papular skin lesions associated with sclerosis and a serum monoclonal gammopathy. Little is known about either the natural history or the systemic manifestations of this disease. We reviewed the medical records of 19 patients with biopsy-proven scleromyxedema seen from 1950 to 1985 for evidence of systemic disease. There were 10 males and 9 females with a median age at diagnosis of 53 years. Monoclonal gammopathy was present in 13 patients. Eight patients complained of dysphagia; 3 had proximal esophageal dysfunction and 1 had total esophageal aperistalsis on barium swallow. Proximal muscle weakness was noted in 5, with an inflammatory myopathy in 3. Six patients complained of dyspnea on exertion. Of these, 5 had reduced diffusing capacity, 3 had reduced volumes, and 2 developed cor pulmonale. Pathologic changes characteristic of "scleroderma kidney" were demonstrated in 1 patient at postmortem. One patient had Raynaud's phenomenon and 2 had arthralgias/arthritis with noninflammatory synovial fluids. Although 8 of 12 patients treated with melphalan noted regression of their skin changes, no consistent improvement in the extracutaneous manifestations was demonstrated. Furthermore, 2 patients died of sepsis related to melphalan-induced myelosuppression, and 4 developed hematological malignancies following melphalan therapy. In conclusion, systemic manifestations in scleromyxedema are more prevalent than previously recognized, and can resemble those of scleroderma. Significant toxicity occurred with the use of alkylating agents in these patients, with treatment-related complications developing in 45% of patients treated with melphalan. The lack of definitive data regarding the natural history of this disease complicates the question of optimal therapy, but the use of alkylating agents should be reserved for those patients with severe debilitating skin disease.

Toxicity of amphotericin B plus flucytosine in 194 patients with cryptococcal meningitis.

A multicenter prospective randomized trial of four versus six weeks of amphotericin B, 0.3 mg/kg per day, plus flucytosine, 150 mg/kg per day, was performed with 194 patients with cryptococcal meningitis. One or more toxic drug reactions developed in 103 patients: azotemia (51), renal tubular acidosis (two), leukopenia (30), thrombocytopenia (22), diarrhea (26), nausea/vomiting (10), and hepatitis (13). The four- and six-week regimens were complicated by toxicity in 44 percent and 43 percent of cases, respectively. Toxicity appeared during the first two weeks of therapy in 56 percent and during the first four weeks in 87 percent. Azotemia did not occur more frequently in renal transplant recipients or diabetic patients. Cytopenias did not appear more often in patients with hematologic malignancies or those receiving immunosuppressive therapies. Toxic reactions that contributed to death developed in five patients (two with azotemia, one with pancytopenia, one with hepatitis, one with ileus). Amphotericin B-induced azotemia was not a significant risk factor for the subsequent development of bone marrow, gastrointestinal, or hepatic toxicity attributable to flucytosine. Flucytosine toxicity was associated with peak serum flucytosine levels of 100 micrograms/ml or more during two or more weeks of therapy (p = 0.005). Peak 5-fluorouracil levels were not predictive of toxicity. An initial dose of flucytosine is recommended based on the creatinine clearance: 150 mg/kg per day at a creatinine clearance above 50 ml/minute, 75 mg/kg per day at a creatinine clearance of 26 to 50 ml/minute, and 37 mg/kg per day at a creatinine clearance of 13 to 25 ml/minute. The serum creatinine level should be monitored twice weekly and the creatinine clearance weekly during therapy in order to anticipate changes in serum flucytosine concentration. In addition, it is recommended that the serum flucytosine level be determined two hours after an oral dose once a week, and that the dose be adjusted to maintain a level of 50 to 100 micrograms/ml.

Treatment of cryptococcal meningitis with combination amphotericin B and flucytosine for four as compared with six weeks.

One hundred ninety-four patients with cryptococcal meningitis were enrolled in a multicenter, prospective, randomized clinical trial to compare the efficacy and toxicity of four as compared with six weeks of combination amphotericin B and flucytosine therapy. Among 91 patients who met preestablished criteria for randomization, cure or improvement was noted in 75 percent of those treated for four weeks and in 85 percent of those treated for six weeks. The estimated relapse rate for the four-week regimen was higher--27 as compared with 16 percent--whereas the incidence of toxic effects for the two regimens was similar--44 as compared with 43 percent. Among 23 transplant recipients, 4 of 5 treated for four weeks relapsed, leading to the decision to treat the rest of the group for six weeks. Only 3 of the 18 treated for six weeks relapsed. In a third group of 80 patients, the protocol was not followed during the initial four weeks, and these patients were not randomized. Thirty-eight died or relapsed. Multifactorial analysis of pretreatment factors for all 194 patients identified three significant predictors (P less than 0.05) of a favorable response: headache as a symptom, normal mental status, and a cerebrospinal fluid white-cell count above 20 per cubic millimeter. These and other findings in this study are consistent with the view that the four-week regimen should be reserved for patients who have meningitis without neurologic complications, underlying disease, or immunosuppressive therapy; a pretreatment cerebrospinal fluid white-cell count above 20 per cubic millimeter and a serum cryptococcal antigen titer below 1:32; and at four weeks of therapy, a negative cerebrospinal fluid India ink preparation and serum and cerebrospinal fluid cryptococcal-antigen titers below 1:8. Patients who do not meet these criteria should receive at least six weeks of therapy.

Clinical trials with Staphylococcus aureus and protein A in the treatment of malignant disease.

Perfusion of plasma from tumor-bearing animals over Staphylococcus aureus with membrane-bound protein A has resulted in significant tumor shrinkage. Similar therapy has now been given to 16 patients by three methods. No tumor responses have been observed. Five patients were treated with perfusion over fixed and killed S. aureus Cowan I. Cardiovascular and respiratory toxicity was excessive and appeared to be related to volume and rate of plasma infused. Eight patients were treated with perfusion of autologous plasmas over protein A-collodion-charcoal. Doses of plasma ranged from 50 to 450 ml. No toxicity was noted. Three patients have been treated with perfusion over protein A-silica. Toxicity in two resembled that seen in the S. aureus trials, although it was not as severe. We conclude that the toxicity of this therapy can be life-threatening, and human trials should be undertaken with caution.

A modification of the canine carotid-jugular shunt.

A shunt modification was used for implantation in the carotid-jugular vessels of the dog. The shunt was made of plastic tubing and was tied to each vessel with three silk ligatures. The tubing was exteriorized and anchored to the skin. The exposed tubing was cut and attached to the input and output lines of a tubing kit for leukapheresis with a continuous flow centrifuge. Surgical implantation of the shunt was accomplished with ease and minimum trauma to the animal. Useful life of the shunt extended over a 3-week period with minimal requirements for anticoagulants.