PubMed Health⌕ Search

Biomedical subjects

C W Fink

Publications and source records attributed to C W Fink.

At least 19 recordsLinked to original sources
PubMed1992

Methotrexate in resistant juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children's Study Group.

BACKGROUND: The antimetabolite methotrexate has been shown in placebo-controlled trials to be effective in adults with rheumatoid arthritis. Methotrexate may also be effective in children with resistant juvenile rheumatoid arthritis, but the supporting data are from uncontrolled trials. METHODS: Centers in the United States and the Soviet Union participated in this randomized, controlled, double-blind trial designed to evaluate the effectiveness and safety of orally administered methotrexate. Patients received one of the following treatments each week for six months: 10 mg of methotrexate per square meter of body-surface area (low dose), 5 mg of methotrexate per square meter (very low dose), or placebo. The use of prednisone (less than or equal to 10 mg per day) and two nonsteroidal antiinflammatory drugs was also allowed. RESULTS: The 127 children (mean age, 10.1 years) had a mean duration of disease of 5.1 years; 114 qualified for the analysis of efficacy. According to a composite index of several response variables, 63 percent of the children who received low-dose methotrexate improved, as compared with 32 percent of those in the very-low-dose group and 36 percent of those in the placebo group (P = 0.013). As compared with the placebo group, the low-dose group also had significantly larger mean reductions from base line in the number of joints with pain on motion (-11.0 vs. -7.1), the pain-severity score (-19 vs. -11.5), the number of joints with limited motion (-5.4 vs. -0.7), and the erythrocyte sedimentation rate (-19.0 vs. -6 mm per hour). In the methotrexate groups only three children had the drug discontinued because of mild-to-moderate side effects; none had severe toxicity. CONCLUSIONS: Methotrexate given weekly in low doses is an effective treatment for children with resistant juvenile rheumatoid arthritis, and at least in the short term this regimen is safe.

Administration, Oral↗
PubMed1992

Intracranial findings in progressive facial hemiatrophy.

There have been infrequent reports of cerebral lesions associated with progressive facial hemiatrophy. Six children with progressive facial hemiatrophy were evaluated. Four were referred for evaluation of neurological deficits: 2 with seizures, one with left hemiparesis and one with learning problems. The remaining 2 patients had only facial hemiatrophy. Cranial computed tomography (CT) in 5 patients revealed the bony and soft tissue defects, but cerebral calcifications were seen in only 3 patients. Cranial magnetic resonance imaging (MRI) demonstrated areas of increased signal in the ipsilateral white matter on T2 weighted images in all 5 patients with upper facial atrophy. Ipsilateral cerebral lesions with progressive facial hemiatrophy may be more common than once believed. MRI sometimes reveals abnormalities of the white matter even in patients without neurologic symptoms, and may be more sensitive than CT in the diagnostic evaluation of patients with progressive facial hemiatrophy.

Adolescent↗
PubMed1991

The role of the streptococcus in poststreptococcal reactive arthritis and childhood polyarteritis nodosa.

Poststreptococcal reactive arthritis is most likely a form of acute rheumatic fever. However, it frequently differs by early development of arthritis after pharyngitis, more prolonged arthritis or arthralgia and a less dramatic response to aspirin. The use of prophylactic penicillin is discussed and advocated. Childhood polyarteritis may be divided into a cutaneous form and a more generalized form that usually involves the kidney but frequently also the gastrointestinal tract, heart, or nervous system. Nine children with polyarteritis nodosa are described and their disease related to a prior streptococcal infection.

Acute Disease↗
PubMed1991

The clinical features, course, prognosis and treatment of juvenile arthritis.

The author's classification of juvenile arthritis (JA) differs from most by utilizing both the type of onset and the disease course separated into individual subgroups. The clinical aspects of each are described in detail, along with the special tests and studies to be done to differentiate them. Particular attention is given to the differences between the four subgroups of the pauciarticular onset group. There are different genetic factors for each subgroup and new data on HLA typing utilizing DNA techniques may be helpful in the prognosis of the disease course. The therapy of JA begins with non-steroidal anti-inflammatory drugs, continues with second-line drugs such as gold and penicillamine, and finally leads to the use of immunosuppressive agents. The range of doses, the maximal dose, and the frequency of administration is given for each medication. The long-term prognosis is generally good, with a low death rate, primarily seen in the systemic onset patients. The causes of death vary around the world. Prognosis for continued joint activity and joint function is determined significantly by the type of onset and is worse in the rheumatoid factor positive polyarticular onset group.

Adolescent↗
PubMed1991

Acute airway obstruction in relapsing polychondritis: treatment with pulse methylprednisolone.

We describe 2 adolescents with relapsing polychondritis who developed acute airway obstruction. Both were successfully treated with intravenous steroids for this complication following failure with oral steroids. Early respiratory tract involvement in younger patients seems predictive of a poor outcome and aggressive therapy with intravenous high dose steroids and/or immunosuppressive drugs appears to be indicated.

Acute Disease↗
PubMed1990

HLA antigens in juvenile arthritis. Pauciarticular and polyarticular juvenile arthritis are immunogenetically distinct.

Using DNA techniques, we investigated the role of HLA-DR, DQ, and DP alleles in susceptibility to juvenile arthritis (JA). We studied 2 groups of patients with JA having a different disease prognosis and course. The pauciarticular form is usually benign, while the polyarticular disease frequently leads to joint destruction and disability. Persistent pauciarticular disease developed preferentially in patients having HLA-DRw13-Dw18 and DQw6-Dw18, but these antigens did not confer susceptibility in patients whose disease converted to the polyarticular form. HLA-DPw2.1 was an additional susceptibility factor for patients with JA of pauciarticular onset. In the polyarticular form of JA, HLA-DPw3 was the major factor for susceptibility, giving a relative risk of 10.3 (P less than 0.0001). In addition, we found that DRw8.1 and DQw4 were increased, and HLA-DR4 was markedly decreased, in patients with pauciarticular and polyarticular disease. These results indicate that in addition to some shared factors, distinct HLA class II alleles are important in pauciarticular or polyarticular JA. We conclude that typing with oligonucleotide probes may be useful in predicting the outcome in some children with arthritis.

Adolescent↗
PubMed1990

Ibuprofen suspension in the treatment of juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group.

Ninety-two children with juvenile rheumatoid arthritis were randomly assigned to treatment in a multicenter, double-blind, 12-week trial designed to compare the efficacy and safety of a liquid formulation of ibuprofen at a dosage of 30 to 40 mg/kg/day versus those of aspirin at a dosage of 60 to 80 mg/kg/day. No significant intergroup differences in response rates or in the amount of improvement in articular indexes of disease activity were observed. More children treated with aspirin discontinued treatment early because of adverse reactions. After this trial, 84 additional patients with juvenile rheumatoid arthritis entered a 24-week, multidose (30, 40, and 50 mg/kg/day), open trial of ibuprofen suspension. Favorable response rates for the three groups were similar, and continued improvement was observed throughout the 24-week period. A dose-response relationship was observed with respect to adverse reactions of the upper gastrointestinal tract. We conclude that ibuprofen suspension is an effective nonsteroidal antiinflammatory drug and that its tolerability in children is acceptable.

Adolescent↗
PubMed1990

Medical treatment of juvenile arthritis.

The range of medications available to treat juvenile arthritis has markedly expanded over the past 15 years. Multiple new nonsteroidal antiinflammatory drugs (NSAIDs) are available in the United States, although only a few are approved for use in children, and none have been proven to be significantly better than aspirin in suppressing inflammation. The average time before significant improvement is noticed is over 30 days in the 50% of the children who respond to any NSAID within three months. The percentage of responders progressively increases with the length of therapy, so treatment should be continued until one is reasonably certain that improvement will not occur before changing medication. In the more severely involved child, gold and other disease-modifying medications are used. However, it has been difficult to prove the value of these medications in controlled studies because of the high rate of significant improvement in the control group treated with NSAIDs. In preliminary studies, methotrexate appears to have significant benefit in children who have failed other treatments. Other newer therapies, such as intravenous gammaglobulin, have only been used in a small number of patients and have not as yet been proven beneficial.

Anti-Inflammatory Agents↗
PubMed1989

Diagnosis of synovial cysts in children by magnetic resonance imaging.

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).

Child↗
PubMed1988

Prognosis of children with poststreptococcal reactive arthritis.

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.

Adolescent↗
PubMed1987

HLA-D region epitopes associated with juvenile arthritis. Recognition by alloreactive T cell clones and alloantisera.

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.

Antibodies, Monoclonal↗
PubMed1986

Oxidation-reduction potentials of butyryl-CoA dehydrogenase.

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)

Butyryl-CoA Dehydrogenase↗
PubMed1986

A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis.

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.

Age Factors↗
PubMed1986

Vasculitis.

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.

Adrenal Cortex Hormones↗
PubMed1986

Septic arthritis and osteomyelitis in children.

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.

Adolescent↗
PubMed1985

Immunogenetic studies of juvenile dermatomyositis. III. Study of antibody to organ-specific and nuclear antigens.

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.

Adolescent↗