Biomedical subjects
Publications and source records attributed to C W Fink.
We describe a 10-year-old girl, who presented with thrombotic thrombocytopenic purpura (TTP) and shortly thereafter developed systemic lupus erythematosus (SLE). The association between TTP and SLE is known, but this is the first report of SLE presenting as TTP.
Synovial cysts complicating inflammatory joint disease are less common in children than in adults. They may present at sites distant from the joint and be mistaken for other conditions. We present 2 children in whom the diagnosis was made using magnetic resonance imaging at medium field strength (0.35 tesla).
Patients with Group A beta-hemolytic streptococcal infection and articular disease who do not fulfill the modified Jones criteria for a diagnosis of acute rheumatic fever (ARF) have been classified as poststreptococcal reactive arthritis/arthralgia. We reviewed the initial clinical characteristics and outcome of 12 poststreptococcal reactive arthritis/arthralgia patients. During the initial episode all had arthritis or arthralgia and a documented streptococcal infection. None had carditis and none received prophylactic antibiotic therapy during an average follow-up of 17 months (range, 6 to 42 months). One patient developed classic ARF with valvulitis 18 months after the initial episode. Two children had later episodes of arthritis and two had at least one additional episode of arthralgia. Poststreptococcal reactive arthritis/arthralgias seems to be part of the disease spectrum of ARF and therefore the use of prophylactic antibiotic therapy to prevent subsequent development of ARF and carditis in these patients should, perhaps, be reconsidered.
The HLA-D region antigens DR5 (w11,w12), DRw6 (w13,w14), DRw8, DRw52, and DQw1 have previously been shown to be increased in frequency in subsets of patients with juvenile arthritis. Since the HLA-D region is complex (composed of at least 3 subregions encoding multiple molecules, each in turn presenting multiple alloantigenic epitopes), we sought to clarify whether one strongly associated factor might explain the previous findings. To search for the pertinent HLA-D region stimulatory epitopes, alloreactive T cells were primed against DR5 and DRw6 haplotypes and cloned by limiting dilution. Three T cell clones and 1 alloantiserum met the criteria for significant association with juvenile arthritis on patient testing, including DR5, DRw6, and DRw8 haplotypes. Monoclonal antibody blocking revealed that all 4 recognized epitopes on DR subregion products. For 2 of the clones, the relative risks for JA (10.5 and 9.4) were higher than the risks with any other previously described typing reagents.
In order to obtain butyryl-CoA dehydrogenase from Megasphaera elsdenii in pure enough form to perform redox studies, the existing purification procedures first had to be modified and clarified [Engel, P. (1981) Methods Enzymol. 71, 359-366]. These modifications are described, and the previously unpublished spectral properties of the electrophoretically pure CoA-free butyryl-CoA dehydrogenase are presented. In our spectral reductive titration of pure enzyme, we show that although blue neutral flavin radical is stabilized in nonquantitative amounts in dithionite titrations (19%) or in electrochemical reductions mediated by methylviologen (5%), it is not thermodynamically stabilized; therefore, only a midpoint potential for butyryl-CoA dehydrogenase is obtained. The electron-transfer behavior from pH 5.5 to pH 7.0 indicates reversible two-electron transfer accompanied by one proton: EFlox + 2e- + H+ = EFlredH- Em7 = -0.079 V vs. SHE where EFlox is oxidized butyryl-CoA dehydrogenase, EFlredH- is two electron reduced enzyme, and Em7 is the midpoint potential at pH 7.0 at 25 degrees C. Redox data and activity data both indicate that the enzyme loses activity rapidly at pH values above 7.0. The Em7 of the butyryl-CoA dehydrogenase is 40 mV positive of the Em7 of the butyryl-CoA/crotonyl-CoA couple [Gustafson, W. G., Feinberg, B. A., & McFarland, J. T. (1986) J. Biol. Chem. 261, 7733-7741]. Binding of substrate analogue acetoacetyl-CoA caused the potential of butyryl-CoA dehydrogenase to shift 100 mV negative of the free enzyme. The negative shift in potential makes electron transfer from enzyme to substrate more probable, which is consistent with the direction of electron transfer in the bacterial system.(ABSTRACT TRUNCATED AT 250 WORDS)
Criteria for the classification of juvenile rheumatoid arthritis were analyzed in a detailed database of 250 children in order to assess the accuracy of diagnosis and validity of onset types and course subtypes. A number of conclusions have been derived from this study: All definitions of the 1973 criteria for classification of juvenile rheumatoid arthritis should be retained. The addition of onset types to the 1976 revision of the criteria has been validated. The course of the disease after the onset period of 6 months is as important to the outcome of a group of children as is the onset type. The current classification should be broadened to include the course subtypes.
Inflammatory changes in blood vessels are a prominent feature of several diseases, which can be categorized by the size of the vessels, the nature of the inflammatory exudate, and the specific organs involved. The clinical and laboratory findings are variable and frequently nonspecific. Therapy ranges from essentially just observation to high-dose steroids combined with immunosuppressive agents, but treatment must be individualized. Early and correct diagnosis is thus important, but because there is considerable overlap between diseases, especially in the leukocytoclastic vasculitis group, one should never delay initiation of therapy while one is trying to finalize the diagnosis, particularly when the patient may be deteriorating rapidly.
Most of the data for this paper were taken from a 30-year follow-up of septic arthritis and a 25 year series of osteomyelitis seen in Dallas, Texas. A specific bacterial aetiology was determined in about 70% of patients with septic arthritis, utilizing culture of multiple fluids. The aetiological agent was influenced by the age of the patient. In the newborn Staph. aureus, group B streptococci and gram-negative organisms are found most commonly. In the older infant H. influenzae becomes a prominent pathogen, and in those over 2 years of age staphylococci, streptococci, H. influenzae and N. gonorrhoea are the predominant organisms. Ninety-three per cent of arthritis was monoarticular. A slightly higher percentage (78%) of children with osteomyelitis had a specific bacterial aetiology determined. Staph. aureus was the most common pathogen found at all ages, averaging 53% of all cases and in all age groups, and followed in frequency by various types of streptococci. Diagnosis was delayed in osteomyelitis compared to septic arthritis. In the Dallas patients a single bone was involved in 316 compared to 24 with polyosteal disease. In both infections the initial antibiotic chosen is determined by the gram strain of material obtained from joint aspiration, pus, or other secretions. If no specific bacterial aetiology is found, treatment is begun for the most likely organism considering the age of the patient and the clinical situation. Recently oral therapy has been used extensively in specific instances after an initial period of parenteral therapy. A limited number of follow-up studies have shown that the age of the patient, the bone and/or joint involved, and the organism responsible all influence the long-term results in both septic arthritis and osteomyelitis. The poorest long-term prognosis is in the neonate, especially where the hip joint is involved either alone or with a concomitant osteomyelitis.
Ninety children with definite juvenile dermatomyositis (JDMS), who had been HLA typed, were tested for the presence of tissue or organ-specific antibodies. Sixty had active disease at the time of study. The mean disease duration was 4 years, and 30 had soft tissue calcifications. The following autoantibodies were sought: thyroid, gastric parietal cells, smooth muscle, striated muscle, microsomes, mitochondria, DNA, extractable nuclear antigen, Sm, PM-1, antinuclear antibody (ANA), and rheumatoid factor. Only the ANA and PM-1 were more frequent in patients than in controls (P less than 0.0002 and P less than 0.001, respectively). Higher levels of immune complexes (P less than 0.01) were found in sera from patients with JDMS than in sera from controls and were correlated with the presence of ANA in patients (P less than 0.01). Soft tissue calcification was not associated with any autoantibody or HLA antigen, but with disease duration and activity (P less than 0.001 and P less than 0.05, respectively). There was no association between the occurrence of any autoantibody and the presence of HLA-B8 or DR3 among the white patients with JDMS. The frequency of autoantibodies in 43 full siblings of children with JDMS was not increased. We conclude that children with JDMS, with or without HLA-B8/DR3, do not show evidence of a generalized nonspecific antibody response to tissue antigens. The significance of the increased antibody to nuclear antigens ANA and PM-1 remains to be determined.
A fatal case of Kawasaki disease with extensive cardiac involvement in an 11-week-old boy is described. Two-dimensional echocardiography revealed enlargement of the left ventricle, left atrium, and aortic root as well as dilatation of the left main coronary artery. Cardiac catheterization revealed both aortic and mitral regurgitation and fusiform dilatation of the proximal segments of the coronary arteries. The clinical course was characterized by multisystem failure and death on day 31 of the illness. Aortic regurgitation is a very rare complication of Kawasaki disease and has been previously reported in one Japanese infant. The pathogenesis of aortic regurgitation in this disease is not known but may be due to aortitis and/or valvulitis. Kawasaki disease should be included as a cause of aortic regurgitation in infants.
Four children with isolated, persistent elevations of serum transaminases were investigated for hepatic disease and followed for 4 to 24 months before serum creatine kinase determinations were obtained and found to be markedly elevated. Evidence of muscle disease was obtained by close questioning, retrospectively, and mild abnormalities were found on physical examination. Review of laboratory tests in our center for 6 months revealed 30 additional cases of anicteric hypertransaminasemia (20% of those with elevated enzymes), only two of which were unexplained by the admitting diagnosis. Serum transaminase values are elevated in a variety of diseases of different organ systems. Creatine kinase determinations may provide the clue to the diagnosis of occult muscle disease in some children with unexplained anicteric hypertransaminasemia.
Altered immune function has previously been reported in children with idiopathic thrombocytopenic purpura (ITP). Some prior studies have shown that acute and chronic ITP might be differentiated by certain immunologic tests. We investigated lymphocyte subsets in 12 children with ITP (six acute and six chronic) using murine monoclonal antibodies. Although the mean percentages of B lymphocytes and total number of T lymphocytes, suppressor T cells, and helper T cells were similar in patients with acute and chronic ITP and in controls, the values for many children with ITP fell outside of the normal range. The distribution of values was similar among the patients with acute and chronic ITP. These results suggest a heterogeneous nature of immune-mediated thrombocytopenia in childhood.
In 2 sisters with congenital camptodactyly and joint effusions, abnormalities in tendons were restricted to the portion within synovial sheaths. This implied a disease of the tenosynovium, rather than one of the tendon itself. In areas of chronic involvement, some tendons were replaced by fibrous tissue. Significant portions of the tendons in fingers with camptodactyly were replaced by hard scars. Congenital camptodactyly is probably the result of an intrauterine tenosynovitis, rather than an isolated congenital anomaly.
Typing for HLA-A and -B antigens was performed on 87 children with definite juvenile dermatomyositis (JDMS). A significantly increased frequency of HLA-B8 (estimated relative risk = 2.8, Pc less than 0.01) was observed among White patients, but not among Blacks or Latin Americans with JDMS. No abnormality of HLA haplotype segregation was observed among 38 healthy siblings of the JDMS probands.
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In this report, solid phase radioimmunoassays that specifically measure IgG rheumatoid factor (RF) and IgM RF in absolute concentrations are described. Polyclonal RF preparations were utilized as standards, and as little as 40 ng/ml of IgG RF and I ng/ml of IgM RF were detected. The IgG RF concentration of 26 seropositive rheumatoid sera was 439 +/ 755 micrograms/ml (mean +/- 1 SD), a level 107 times that of normal controls (P less than 0.001). In contrast, levels for 49 children with juvenile rheumatoid arthritis (JRA) were 6.1 +/- 3.7 micrograms/ml for those with a polyarticular onset (JRA-Po), and 27.3 +/- 113 micrograms/ml for the pauciarticular group (JRA-Pa), and 12.6 +/- 20.7 micrograms/ml for the group with a systemic onset (JRA-S). None of these values differed significantly from the value of 6.0 +/- 3.9 micrograms/ml measured in a juvenile control group. The IgM RF level in adult rheumatoid arthritis (RA) of 175 +/- 221 micrograms/ml was also significantly elevated compared to controls (P less than 0.001). In JRA, however, mean levels of 1.4 +/- 2.0 micrograms/ml (JRA-Po), 2.8 +/- 8.3 micrograms/ml (JRA-Pa), and 1.1 +/- 0.7 micrograms /ml (JRA-S) were not elevated significantly above the value of 1.2 +/-1.2 micrograms/ml measured in the juvenile control group. Hidden IgM RF was not found in 9 JRA sera tested. These marked differences in RF levels provide another indication that adult RA and JRA are distinct diseases.