Pediatrics

The bacteriologic and clinical effects of early antibiotic treatment of Campylobacter jejuni enteritis were studied. Erythromycin rapidly eliminated C. jejuni from stools, whereas trimethoprim-sulfamethoxazole did not. Despite its bacteriologic effectiveness, erythromycin did not reduce the duration or severity of diarrhea, abdominal pain, or other symptoms.

Human parvovirus B19 infection is occasionally associated with acute lymphocytic myocarditis (ALM). Three infants with B19 virus-associated ALM were followed up clinically, histologically, and immunovirologically. Each infant had B19 virus DNA in the blood or B19 virus-specific IgM antibodies. Two infants with postnatal infection recovered after immunosuppressive therapy. The third infant with possible prenatal infection developed chronic persistent myocarditis associated with persistent B19 virus DNA in the blood. All 3 infants had increased levels of interferon-g, tumor necrosis factor-a, and interleukins -6 and -8. Four newborns with congenital B19 virus infection and 4 infants and children who had postnatally acquired B19 virus infection without myocarditis all had normal levels of these cytokines. These observations suggest that B19 virus infection in infancy causes ALM in some infants and children.

The long-term consequences of parvovirus 61 9 infection in transfusion recipients are not known, and thus the value of 619 screening of blood donors remains unresolved. Hemophiliacs, at risk for 61 9 through their chronic exposure to clotting factor concentrates, have frequent, close medical follow-up and thereby constitute an ideal group in which to study the hematologic sequelae of 61 9 infection. Study Design and Methods: An enzyme-linked immunosorbent assay was used to detect 619 IgG and IgM and the polymerase chain reaction was used to detect 61 9 DNA in frozen, stored plasma samples, obtained between 1987 and 1994, from 136 subjects with hemophilia, including 71 who were human immunodeficiency virus (HIV)-positive and 65 who were HIV-negative. Then the results of the tests were compared with clinical hematologic data and blood product usage data. Results: 619 seroprevalence in the hemophilic cohort was 81.6 percent (111/136), including 74.6 percent (53/71) of HIV-positive and 89.2 percent (58/65) of HIV-negative hemophiliacs. It was not affected by age, type or severity of hemophilia, HIV status, CD4 number, or yearly blood product usage. Only 1 (0.7%) of the 136 samples was positive for 619 IgM and none was positive in polymerase chain reaction for 619 DNA. After adjusting for HIV status, there were no differences between 619positive and 61 9-negative hemophiliacs in hematologic values, CD4 counts, or blood product use. Conclusion: Although 61 9 IgG seroprevalence in this hemophilic cohort is high and indicative of past B19 infection, there is no detectable 61 9 viral activity or any associated long-term clinical or hematologic sequelae.

Five hundred thirty-three liver transplant recipients were seen for follow-up care over a 6-month period. Of these, 23 (4.3%) had a hemoglobin level of < or = 9 g/dl, with 19 being eligible for inclusion in this study. The median hemoglobin level was 8.7 g/dl. Two patients had iron-deficiency anemia. All of the patients were on therapeutic drugs which can suppress erythropoiesis or shorten the lifespan of mature erythrocytes. Six patients (31.6%) were viremic for human parvovirus B19 but none was B19 immunoglobulin M seropositive. Two patients were immunoglobulin M seropositive for cytomegalovirus. The patients with circulating B19 DNA were not easily distinguished from those without the virus by their laboratory results. The absence of reticulocyte counts for these patients contributed to this inability to differentiate B19 from other causes of anemia, particularly drug myelotoxicity. The high likelihood of making a specific diagnosis with the increasing availability of PCR shou...

Pharmacopeial Forum 33(3) [May-June 2007] included a Stimuli article titled "Proposed Change to Acceptance Criteria for Dissolution Performance Verification Testing." This Stimuli article proposed changing the form of the acceptance criteria for the Performance Verification Test (PVT) associated with USP Dissolution <711> to make the PVT consistent with the International Organization for Standardization's recommendations for proficiency testing. The article elicited five comments, which are abstracted here with USP responses.

A 13-month-old Caucasian female presented with erythema, swelling, and pain of the left periorbital region. On admission, her vital signs were normal, and complete blood count did not reveal abnormalities. Blood and eye cultures were collected. On physical examination, the left eye was erythematous and edematous starting at the left medial canthus, tracking across the upper lid to the lateral angle of the eye, and extending inferiorly to involve the medial portion of the lower lid. A pinpoint sinus tract was visible on the medial aspect of the upper eyelid and was actively draining serosanguinous fluid. Head computed tomography demonstrated findings consistent with left preseptal orbital cellulitis and a small developing phlegmon. Patient was started on intravenous broad-spectrum antibiotics but failed to improve after 3 days. Incision and drainage were performed, which revealed a live 1-cm larva.

Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to the recommendations within this guideline to be voluntary, with the ultimate determination regarding their application to be made by the health care provider in light of each patient's individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed and endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice. ACR recommendations are not intended to dictate payment or insurance decisions. These recommendations cannot adequately convey all uncertainties and nuances of patient care. The American College of Rheumatology is an independent, professional, medical and scientific society that does not guarantee, warrant, or endorse any commercial product or service. Objective. To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA). Methods. Pediatric rheumatologists, ophthalmologists with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a systematic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A group consensus process was used to compose the final recommendations and grade their strength as conditional or strong. Results. Due to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recommended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors. Regular ophthalmic monitoring of children with uveitis is recommended, and intervals should be based on ocular examination findings and treatment regimen. Ophthalmic monitoring recommendations were strong primarily because ACR/AF GUIDELINE FOR JIA-ASSOCIATED UVEITIS | 865 of concerns of vision-threatening complications of uveitis with infrequent monitoring. Topical glucocorticoids should be used as initial treatment to achieve control of inflammation. Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors adalimumab and infliximab are recommended when systemic treatment is needed for the management of uveitis. The timely addition of nonbiologic and biologic drugs is recommended to maintain uveitis control in children who are at continued risk of vision loss. Conclusion. This guideline provides direction for clinicians and patients/parents making decisions on the screening, monitoring, and management of children with JIA and uveitis, using GRADE methodology and informed by a consensus process with input from rheumatology and ophthalmology experts, current literature, and patient/parent preferences and values.

We applied a machine learning method of model-based boosting to select clinical parameters which have a relevant impact on treatment decisions in each of the three episodes and compared the results with multiple logistic regression models. Results: N=1781 biologic-naive patients were included during 2001-3, n=2781 in 2004-6 and n=4951 after 2008. The proportion of patients included with the start of a bDMARD was consistently between 60-62%. Patient characteristics at start of the first bDMARD changed over time. Mean disease duration decreased from 11.9 to 9.1 years, mean number of DMARD failures declined from 3.6 to 2.2 and mean disease activity (DAS28) fell from 6.0 to 5.0. The proportion of patients with osteoporosis declined from 24.5% to 11.9%. High disease activity (DAS28), prior DMARD failures and high doses of glucocorticoids (GC) were associated with starting a biologic treatment independent from the enrollment year. Over time, more patients with only moderate disease activity, lower doses of GC and positive rheumatoid factor as well as those with more severe comorbidities like heart failure and chronic renal disease were included in the bDMARD cohort. Male sex was associated with the start of bDMARD in 2001-2003 but the effect receded in recent years of enrollment. Conclusions: The increasing use of biologics in patients with moderate disease activity and GC treatment shows that new treatment guidelines recommending earlier use during disease course to prevent further damage are realized in daily care practice. Growing knowledge and experience with biologics increasingly allows rheumatologists to treat also patients with serious comorbidities like heart failure.

Objectives-To use consensus methods and the considerable expertise contained within the Children's Arthritis and Rheumatology Research Alliance (CARRA) organization, to extend the 3 previously developed treatment plans for moderate juvenile dermatomyositis (JDM) to span the full course of treatment. Methods-A consensus meeting was held in Chicago on April 23-24, 2010 involving 30 pediatric rheumatologists and 4 lay participants. Nominal group technique was used to achieve consensus on treatment plans which represented typical management of moderate JDM. A preconference survey of CARRA, completed by 151/272 (56%) members, was used to provide additional guidance to discussion. Results-Consensus was reached on timing and rate of steroid tapering, duration of steroid therapy, and actions to be taken if patients were unchanged, worsening, experiencing medication side effects or disease complications. Of particular importance, a single, consensus steroid taper was developed. Conclusions-We were able to develop consensus treatment plans which describe therapy for moderate JDM throughout the treatment course. These treatment plans can now be used clinically, and data collected prospectively regarding treatment effectiveness and toxicity. This will allow comparison of these treatment plans and facilitate the development of evidence-based treatment recommendations for moderate JDM.

Background: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA). Methods: The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting.

Objective: To characterize uterine mast cells and investigate uterine muscle strips contractile responses to challenge with an allergen in nonpregnant and pregnant women. Study design: A double-antibody labeling technique was used to identify tryptase positive or chymase-tryptase-positive mast cells in uterine samples from term pregnant and nonpregnant women. Longitudinal myometrial strips were prepared from biopsies of hysterectomy specimens from patients undergoing procedures for benign indications and women who had elective cesarean sections. Responses to ragweed antigen were compared in uterine tissues from allergic and nonallergic patients and with passively sensitized tissues in the absence or presence of H 1 receptor antagonist and a cyclooxygenase inhibitor. Results: Tryptase-chymase-positive mast cells were predominant in nonpregnant myometrium, whereas tryptase-positive cells were dominant in pregnant myometrium. Mast cell density was significantly higher in tissue from pregnant women than those of nonpregnant women. Studies in tissues from patients with known allergy to ragweed, as well as in passively sensitized tissues, showed an immediate and substantial increase in the frequency and force of myometrial contraction after a challenge with ragweed antigen. A similar response was observed to histamine. There was no contractile response to antigen challenge in tissues from nonallergic patients. An H 1 receptor antagonist partially inhibited the response to antigen, whereas a cyclooxygenase inhibitor had no effect. Conclusion: Sensitized isolated pregnant and nonpregnant human uterine tissue is capable of responding to antigen challenge with strong myometrial contractions. This ability, along with the increased density of mast cells in pregnant tissues as compared with nonpregnant tissues, indicates a possible role for mast cells in mediating uterine contractility in pregnancy.

Background: Allergic eye disease is common, but little is known about the underlying disease mechanisms. Conjunctival allergen challenge causes symptoms similar to those of seasonal allergic conjunctivitis and is a useful model to study. Objective: We have used allergen challenge to investigate the course of the ocular response, tear inflammatory mediators, tissue adhesion protein expression, and cellular infiltration. Methods: Eighteen atopic patients and 4 nonatopic control subjects were challenged with extracted mixed grass or Dermatophagoides pteronyssinus in one eye and control vehicle in the other. The clinical response was recorded, and tears were collected over a 6-hour period. Conjunctival biopsy specimens were taken from the challenged eye at 6 or 24 hours. Results: An early-phase response (maximal at 20 minutes) showed a significant increase in tear histamine and tryptase levels, reducing to control levels again by 40 minutes. At 6 hours, a late-phase response occurred with increased symptoms, a second peak of tear histamine and eosinophil cationic protein but not tryptase, upregulation of the adhesion molecules E-selectin and intercellular adhesion molecule, and a cellular infiltrate of mast cells, neutrophils, eosinophils, macrophages, and basophils, with T cells increased only in bulbar biopsy specimens. Conclusions: The early peaks of tear histamine plus tryptase indicate that the mast cell is responsible for the early-phase response, but basophils may be involved in the late-phase response. Both tear and biopsy findings underline the significance of the late-phase response as the transition between a type I response and clinical disease. (J Allergy Clin Immunol 2000;106:948-54.)

Objective: To assess the role of basophils in allergic asthma, we measured the number of basophils in the bronchial mucosa and their capacity to express IL-4 mRNA and protein during allergen-induced late asthmatic responses. Methods: Fiberoptic bronchoscopic bronchial biopsies were obtained at 24 hours from sites of segmental bronchial allergen challenge and control sites in 19 patients with atopic asthma and 6 nonatopic healthy volunteers. Basophil numbers were assessed by immunohistochemistry through use of mAb 2D7. IL-4 mRNA-positive cells were detected through use of in situ hybridization and colocalized to basophils through use of sequential immunohistochemistry/in situ hybridization. IL-4 protein was detected and colocalized to basophils through use of dual immunohistochemistry. Results: After allergen challenge, there was an increase in the median number of 2D7-positive basophils per square millimeter in the bronchial mucosa in patients with asthma (0.9 cells/mm 2 at baseline to 8.8 cells/mm 2 after challenge; P = .002), which also was significantly higher than what was seen in nonasthmatic controls (P = .01). Similarly, IL-4 mRNApositive cells were increased at 24 hours in patients with asthma (1.4 to 14) in comparison with controls (0 to 0; P = .02). Colocalization studies revealed that 15% and 41% of the basophil population in patients with asthma after allergenchallenge expressed, respectively, IL-4 mRNA and protein.

The immunohistology of the nasal mucosa was examined in 13 grass pollen-sensitive patients and in seven normal nonatopic control subjects before and during the pollen season. Cryostut sections (6 km) of biopsy specimens from the inferior turbinate were immunostained with the alkaline-phosphatase antialkaline-phosphatase method and a panel of monoclonal antibodies. Mast cell subtypes were measured with a double sequential immunostaining method. Within the submucosa, seasonal increases in total (MBP', p < 0.01) and "activated" (EG2-, p < 0.01) eosinophils were observed for the patients, which were significant when these counts were compared with counts for those of control subjects (MBP' p < 0.01; EG2' p < 0.001). Within the nasal epithelium, seasonal increases in total (p < 0.05) and "activated" (p < 0.02) eosinophils were also observed. Mast cell counts revealed seasonal increases in tryptase-only positive mast cell (MC=) (p < 0.02) but not chymase plus tryptase-positive mast cells (MC.,(-) waithin the epithelium that were significant when counts were compared with those of control subjects (p < 0.03). No significant changes were observed within the submucosa or epithelium .for total leukocytes (CD45' cells) or T-lymphocytes (CD3+, CD4+, CD8'. and CD 2.5" cells) ,for either group. Similarly, no sign&ant changes were observed for neutrophils (antielastase), macrophages (CD68+), nor HLA-DR' cells. In the subjects with rhinitis, seasonal submucosul CD3' counts correlated with MBP' eosinophils (r = 0.56; p < 0.05) and M&s (r = 0.65; p < 0.02). Similarly, seasonal epithelial EG2 + eosinophil counts correlated with MC, s (r = 0.56; p < 0.05). The results indicate that seasonal allergic rhinitis is associated with local accumulation of "activated" eosinophils and the epithelial migration of MC,-s but not MC,s during natural grass-pollen exposure. (J AUERGY CLIN IMMUNOI. 1992:89;877-83.)