First Measurement of the Nuclear-Recoil Ionization Yield in Silicon at 100 eV.

We measured the nuclear-recoil ionization yield in silicon with a cryogenic phonon-sensitive gram-scale detector. Neutrons from a monoenergetic beam scatter off of the silicon nuclei at angles corresponding to energy depositions from 4 keV down to 100 eV, the lowest energy probed so far. The results show no sign of an ionization production threshold above 100 eV. These results call for further investigation of the ionization yield theory and a comprehensive determination of the detector response function at energies below the keV scale.

Constraints on Lightly Ionizing Particles from CDMSlite.

The Cryogenic Dark Matter Search low ionization threshold experiment (CDMSlite) achieved efficient detection of very small recoil energies in its germanium target, resulting in sensitivity to lightly ionizing particles (LIPs) in a previously unexplored region of charge, mass, and velocity parameter space. We report first direct-detection limits calculated using the optimum interval method on the vertical intensity of cosmogenically produced LIPs with an electric charge smaller than e/(3×10^{5}), as well as the strongest limits for charge ≤e/160, with a minimum vertical intensity of 1.36×10^{-7} cm^{-2} s^{-1} sr^{-1} at charge e/160. These results apply over a wide range of LIP masses (5 MeV/c^{2} to 100 TeV/c^{2}) and cover a wide range of ßγ values (0.1-10^{6}), thus excluding nonrelativistic LIPs with ßγ as small as 0.1 for the first time.

Light Dark Matter Search with a High-Resolution Athermal Phonon Detector Operated above Ground.

We present limits on spin-independent dark matter-nucleon interactions using a 10.6 g Si athermal phonon detector with a baseline energy resolution of σ_{E}=3.86±0.04(stat)_{-0.00}^{+0.19}(syst) eV. This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from 93 to 140 MeV/c^{2}, with a raw exposure of 9.9 g d acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches.

Juvenile arthritis, HLA-A2 and binding of DEK oncogene-peptides.

Previous studies have shown that susceptibility to Pauciarticular Juvenile Arthritis is associated with HLA-A*0201. Recently, autoantibodies against the protein of the DEK oncogene have been found in sera of patients with this disease. If T cells are involved in the pathogenesis of joint lesions, it is possible that they target autoantigens presented by HLA-A*0201. Therefore, we investigated whether DEK-derived peptides can bind efficiently to HLA-A*0201. Nonameric peptides selected considering anchor positions 2 and 9, and preferred amino acids at other positions, were incubated either with the human TAP-deficient cell line 174CEM.T2 (T2) or with the homozygous B cell line JESTHOM (A*0201, B*2705, Cw1), previously depleted of endogenous peptides. Binding was measured as the increase of detection of fully assembled, HLA-A*0201 molecules by flow cytometry with the anti-HLA-A2 monoclonal antibody (mAb) BB7.2. Three out of ten selected DEK-derived peptides showed binding to HLA-A*0201, which was peptide concentration-dependent (1 microM to 100 microM). DEK155-163 (AMLKSICEV), which also has two preferred amino acid residues at positions 6 and 8, yielded the highest binding. DEK163-171 (VLDLERSGV) and DEK72-80 (SLQREPFTI), which also has one preferred amino acid residue at position 8, also were able to bind to HLA-A*0201. Furthermore, peptide-induced, fully assembled, HLA-A*0201 molecules were immunoprecipitated with the BB7.2 mAb from metabolically-labeled T2 cells incubated with DEK72-80, DEK155-163, and DEK163-171. A faint band was observed in the immunoprecipitates of cells incubated with DEK65-73 (it carries a preferred amino acid residue at position 6), suggesting that this peptide interacts weakly with HLA-A*0201. These results indicate that several nonameric peptides derived from the DEK protein can bind to HLA-A 0201 and suggest that the complexes formed may be able to stimulate CD8+ T cells in patients with Pauciarticular Juvenile Arthritis.

Juvenile dermatomyositis at diagnosis: clinical characteristics of 79 children.

OBJECTIVE: To evaluate demographic and clinical characteristics, duration of time between disease onset (date of first rash and/or weakness), and diagnosis/therapy, as well as socioeconomic status, of children with newly diagnosed juvenile dermatomyositis (JDM). METHODS: Structured telephone interview of families of a cohort of 79 children with JDM: interval between onset of symptoms to diagnosis, median of 3 months (range 0.5-20.0). RESULTS: At diagnosis, all the children had rash (100%) and proximal muscle weakness (100%); 58 (73%) had muscle pain; 51 (65%) fever; 35 (44%) dysphagia; 34 (43%) hoarseness; 29 (37%) abdominal pain; 28 (35%) arthritis; 18 (23%) calcinosis, and 10 (13%) melena. Muscle derived enzymes were normal in 10% of the children. Of the 43 children who had an electromyogram (EMG), 8 (19%) had normal results. Fifty-one children had a muscle biopsy; the results were normal/nondiagnostic in 10 (20%). Median time from disease onset to diagnosis was different between racial groups: Caucasians (n=59) 2.0 months: for minorities (n=20), 6.5 months, (p=0.0008). The median time from disease onset to therapy was: Caucasians. 3.0 months; minorities, 7.2 months (p=0.002). Report of calcinosis was associated with increased time to diagnosis and therapy (p=0.04). In the 33 children whose first symptom occurred in June-September, rash preceded or accompanied onset of muscle weakness in 83% (n=27). Ninety-one percent of the children were given steroid therapy and 9% received methotrexate as well. CONCLUSION: The results of an undirected site for muscle biopsy or EMG may not be diagnostic. Minority children had a longer interval between first JDM symptom and diagnosis/therapy than Caucasian children. Delay in diagnosis/therapy was associated with calcinosis.

New-onset juvenile dermatomyositis: comparisons with a healthy cohort and children with juvenile rheumatoid arthritis.

OBJECTIVE: To determine, in a case-control study, if patients with new-onset juvenile dermatomyositis (juvenile DM) have increased symptoms prior to onset, exposure to certain environmental conditions, frequency of familial autoimmune diseases, or antibody titers, compared with 2 control groups. METHODS: A structured interview with the families of 80 children with juvenile DM, 40 children with juvenile rheumatoid arthritis (JRA), or 23 healthy children, from the same geographic area as the children with juvenile DM, was conducted. All children's sera were tested for antibody to Toxoplasma gondii, herpes simplex virus (HSV), or coxsackievirus B (CVB). RESULTS: A high proportion of children with juvenile DM had constitutional symptoms 3 months before the disease-onset date (P = 0.013 versus control children). Children with JRA had more relatives with rheumatoid arthritis (P = 0.0001) and pernicious anemia (P = 0.003) than did children with juvenile DM or healthy children. Among children < or =7 years of age, elevated enteroviral titers were more frequent in those with juvenile DM (81%) and in healthy controls (90%) than in those with JRA (64%), suggesting a common environmental exposure. Titers to T gondii, HSV, or CVB 1-6 were normal. CONCLUSION: Frequencies of familial autoimmune disease, exposure to environmental factors, or elevated antibody titers to T gondii, HSV, or CVB are not increased in juvenile DM. Children with juvenile DM do have symptoms of illness 3 months before the disease-onset date, and young patients have elevated enteroviral titers, as do young geographic controls.

Actinomycotic splenic abscesses presenting with arthritis.

An 18-month-old Caucasian female began with a high fever. She developed swelling in one finger and one toe. Abdominal ultrasound revealed multiple abscesses in her spleen. Multiple blood culture and splenic abscess aspirations grew no pathogens. She had transient response to multiple antibiotics and splenic abscess drainage, but fever returned along with subcutaneous nodules. Culture of splenic tissue from her second splenic drainage eventually grew one organism identified as Actinomyces naeslundii. Therapy with high dose penicillin followed by amoxicillin p.o. and total splenectomy led to complete recovery.

Early onset sarcoidosis: not a benign disease.

There are 2 distinct forms of sarcoidosis in childhood. We describe the clinical picture of 6 patients with sarcoidosis of the early onset type. All patients had their disease onset during the first 4 years of life. In contrast to the black predominance reported in adult patients, our series comprised 5 whites and one Latin-American. The triad of rash, arthritis, and uveitis seems to be characteristic for this form. The symptoms in our patients were comparable to those in the literature. However, a long followup (9-23 yrs) allowed us to recognize severe complications of the disease, previously not well known, such as blindness (4 patients), growth retardation (3 patients), heart involvement (2 patients), renal failure (1 patient), and even death in one patient. Pulmonary involvement was present only in one patient late in the disease course. This condition may be overlooked, and is sometimes misdiagnosed, due to its rarity and to its similarities with juvenile arthritis. However, the clinical characteristics of the 2 diseases are different. Early and correct diagnosis is important in light of the severe disease prognosis, and the possible therapeutic options.

The articular prognosis of pauciarticular onset juvenile arthritis is not influenced by the presence of uveitis.

OBJECTIVE: The purpose of our retrospective study was to determine the longterm articular prognosis in patients with pauciarticular onset juvenile arthritis (JA) with and without uveitis. METHODS: Twenty-nine patients with pauciarticular onset JA with uveitis were compared to 86 without uveitis, matched for sex, age at disease onset, and duration of followup. All patients had a minimum followup of 6 years from disease onset. The outcome of arthritis was evaluated by: (1) progression to polyarticular disease; (2) hip involvement; (3) radiographic evidence of articular erosions; (4) significant functional disability at the last visit. RESULTS: There was no statistically significant difference between the 2 groups in the severity variables considered, single or combined. CONCLUSION: Our data suggest that the presence of uveitis does not influence the longterm articular prognosis in pauciarticular onset JA.

Clinical and genetic evidence that juvenile arthritis is not a single disease.

Ample evidence shows that what was formerly called "juvenile rheumatoid arthritis" is not a single disease. At least six separate diseases were included as subgroups or subtypes of juvenile rheumatoid arthritis in other classifications. The clinical and laboratory features that differentiate these diseases are discussed. Genetic differences, primarily within the HLA system but also for T-cell receptor genes are described and correlated with the new clinical classification of arthritis.

Nonsteroidal antiinflammatory drug-induced gastroduodenal injury in children.

OBJECTIVE: To determine the incidence of abdominal pain and gastroduodenal injury in children with arthritis taking nonsteroidal antiinflammatory drugs (NSAIDs). METHODS: A retrospective review of the records of all children (570 patients) receiving followup care in an academic rheumatology clinic between 1991 and 1993 was performed. RESULTS: There were 344 patients who used NSAIDs during the study period. Abdominal pain was recorded in 27.9% of patients taking NSAIDs and 14.6% of patients not taking NSAIDs. Abdominal pain in 47 patients (49%) taking NSAIDs and 14 patients (42%) not taking NSAIDs was evaluated radiographically and/or endoscopically. Among those patients evaluated, gastric or duodenal injury was found in 16 (34.0%) who were taking NSAIDs and 1 (7.1%) who were not. This represented a relative risk for gastroduodenal injury of 4.8 for patients taking NSAIDs (P = 0.09). The incidence of injury did not change when analyses were controlled for prednisone or slow-acting antirheumatic drug use. None of the children were hospitalized or died as a result of gastroduodenal injury during the 3-year period. CONCLUSION: We conclude that NSAID use in children with arthritis frequently leads to gastroduodenal injury, with an estimated incidence and relative risk that are comparable to the rates found in adults with arthritis taking NSAIDs, but that hospitalization or death as a result of this injury is uncommon.

Back pain as the presenting symptom in juvenile dermato/polymyositis.

Juvenile dermato/polymyositis is an inflammatory myopathy that usually presents with symmetrical hip and shoulder girdle muscle weakness, with or without a skin rash. In our series of 78 patients with dermato/polymyositis, we found eight children whose initial complaint was back pain, a rare symptom at the onset of other pediatric rheumatic diseases. This unusual presentation significantly delayed the correct diagnosis in most of our cases.

HLA associations in juvenile arthritis.

This review of the current status of HLA associations in juvenile arthritis begins with a discussion of the terms used to identify these patients and an approach for their clinical classification. The authors suggest that seven different types should be identified on the basis of clinical features and associated immunogenetic factors and that each of them should be recognized and called by a separate name. Different combinations of patients have been included in the studies performed in different cities and this fact may explain some of the observed differences in HLA associations in various reports. Results from an on-going study in Dallas are compared with published reports from Prague, Cincinnati, and Houston. HLA alleles associated with susceptibility in pauciarticular patients include certain DR and DQ alleles, one DP allele (DPB1*0201) and one HLA class I allele (HLA-A*0201). Susceptibility for polyarticular onset disease was found by the authors to be uniquely associated with DPB1*0301. Important interactions were observed between alleles at the different loci, with markedly increased odds ratios when combinations of susceptibility alleles were analyzed. The possibility that interaction between class I and class II susceptibility factors might be due to the effect of an allele at one of the TAP loci was examined by probing for polymorphic variants of the TAP1 and TAP2 genes. In addition, class I alleles associated with resistance for the development of juvenile arthritis were discussed. The main allele associated with rheumatoid arthritis (DRB1*0401) appears to be protective for the development of several forms of arthritis prevalent in children.

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.

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.

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.

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.