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.

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.

Canine allogeneic bone marrow transplantation. Technique and variables influencing engraftment.

We have studied the toxicity and immune suppression of supralethal total body irradiation (800-2000 rads, 60Co) at three dose intensities (10 rads/min, 49 rads/min, and 100 rads/min). In 79 intensively supported radiation control animals, the LD50(5) (tn 5 days) for these dose intensities is estimated to be 1556, 941, and 921 rads, respectively. A biomodal pattern of early (median 4 days) and late (median 9 days) deaths was observed corresponding to histopathological evidence of the intestinal and hematopoietic radiation syndromes. Random donor bone marrow transplants were performed in 83 animals to test immune suppression afforded by 800 rads and 1000 rads at dose intensities of either 10 rads/min or 49 rads/min. Bone marrow cell dose was varied to analyze its effect on engraftment. A greater degree of immunosuppression with less toxicity was achieved at the lower dose intensity. A minimum dose of 3-5 X 10(8) nucleated allogeneic bone marrow cells/kg (readily obtainable from living donors) resulted in a high percentage of engraftment with lethal graft-versus-host disease following conditioning with 1,000 rads midplane at 10 rads/min, the optimum regimen employed.

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.

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.

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.

Studies of the Pelger-Huët anomaly in foxhounds.

An inbred family of foxhounds with four members expressing the Pelger-Huët (P-H) anomaly is described. The disease-free status of all P-H affected dogs suggests a benign disorder, although review of breeding records indicated a lower percentage of pups weaned (63%) by P-H females compared with the percentage of pups weaned (81%) by outcrossed females throughout the foxhound colony. Light-microscopic examination of blood films from affected dogs revealed 50--67% neutrophils with round, oval, or bean-shaped nuclei and rarely (0.5%) segmented nuclei. Neutrophils examined by electron microscopy showed the nuclei to have a fine nuclear cleft and condensed chromatin and the cytoplasm to have mature heterochromatic granulation. Local P-H neutrophil mobilization through a standard skin abrasion into a chamber containing autologous serum was impaired at all time periods evaluated (1, 4, 8, and 24 hours) compared with the neutrophil mobilization by normal dogs. Antibody response to sheep erythrocyte immunization was also impaired. In vitro reactivity of normal and P-H lymphocytes stimulated by pokeweed mitogen was depressed when lymphocytes were cultured in plasma from a P-H dog but not when cultured in plasma from a normal dog. Vigorous blastogenic responses to phytohemagglutinin by normal and P-H lymphocytes cultured in P-H or normal plasma suggest the presence of a factor(s) in the P-H plasma which interferes with B-lymphocyte reactivity.

Rosette formation by canine peripheral blood lymphocytes.

The surface membrane characteristics of canine peripheral blood lymphocytes were investigated using erythrocyte (E) and erythrocyte antibody complement (EAC) rosette assays and immunofluorescent staining techniques. Canine thymus-derived lymphocytes formed nonimmune E rosettes with human and guinea pig erythrocytes at approximately the same percentages (mean percentage 36.3 and 32.4, respectively). Rosettes did not form with erythrocytes from seven other animal species. Cell surface immunoglobulins were demonstrable in a small percentage (4%) of the E rosette-forming lymphocyte population. Fragments of human erythrocytes inhibited E rosette formation by intact human red cells, but did not result in a significant decrease in rosette formation by intact guinea pig erythrocytes; likewise, guinea pig fragments had no inhibitory effect on rosette formation by human erythrocytes, demonstrating that separate receptors were required for the two red cell types. EAC rosette formation was not affected by addition of intact or fragmented human and guinea pig erythrocytes. Canine bone marrow-derived lymphocytes were characterized by immunoglobulin on the cell surface and EAC rosette formation. Serial tests of lymphocytes from one dog revealed a wide variation in percentage of cells forming E and EAC rosettes. A close correlation was observed between the immunoglobulin-bearing cells (mean percentage 46.6) and those forming EAC rosettes (mean percentage 49.3).