Two cyclooxygenase isozymes, COX-1 and -2, are known to catalyze the rate-limiting step of prostaglandin synthesis and are the targets of nonsteroidal antiinflammatory drugs. Here we describe a third distinct COX isozyme, COX-3, as well as two smaller COX-1-derived proteins (partial COX-1 or PCOX-1 proteins). COX-3 and one of the PCOX-1 proteins (PCOX-1a) are made from the COX-1 gene but retain intron 1 in their mRNAs. PCOX-1 proteins additionally contain an in-frame deletion of exons 5–8 of the COX-1 mRNA. COX-3 and PCOX mRNAs are expressed in canine cerebral cortex and in lesser amounts in other tissues analyzed. In human, COX-3 mRNA is expressed as an ≈5.2-kb transcript and is most abundant in cerebral cortex and heart. Intron 1 is conserved in length and in sequence in mammalian COX-1 genes. This intron contains an ORF that introduces an insertion of 30–34 aa, depending on the mammalian species, into the hydrophobic signal peptide that directs COX-1 into the lumen of the endoplasmic reticulum and nuclear envelope. COX-3 and PCOX-1a are expressed efficiently in insect cells as membrane-bound proteins. The signal peptide is not cleaved from either protein and both proteins are glycosylated. COX-3, but not PCOX-1a, possesses glycosylation-dependent cyclooxygenase activity. Comparison of canine COX-3 activity with murine COX-1 and -2 demonstrates that this enzyme is selectively inhibited by analgesic/antipyretic drugs such as acetaminophen, phenacetin, antipyrine, and dipyrone, and is potently inhibited by some nonsteroidal antiinflammatory drugs. Thus, inhibition of COX-3 could represent a primary central mechanism by which these drugs decrease pain and possibly fever.

https://www.pnas.org/content/pnas/99/21/13926.full.pdf

COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression

Evidence-based guidelines for the management of patients with Lyme disease, human granulocytic anaplasmosis (formerly known as human granulocytic ehrlichiosis), and babesiosis were prepared by an expert panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 31[Suppl 1]:1-14). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. For each of these Ixodes tickborne infections, information is provided about prevention, epidemiology, clinical manifestations, diagnosis, and treatment. Tables list the doses and durations of antimicrobial therapy recommended for treatment and prevention of Lyme disease and provide a partial list of therapies to be avoided. A definition of post-Lyme disease syndrome is proposed.

/pdf/the-clinical-assessment-treatment-and-prevention-of-lyme-xajvcef2ye.pdf

The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America

http://science.sciencemag.org/content/sci/168/3934/939.full.pdf

Cryobiology: The Freezing of Biological Systems

Transition from child-centered to adult health-care systems for adolescents with chronic conditions: A position paper of the Society for Adolescent Medicine

Background We evaluated the safety and efficacy of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein, in children with polyarticular juvenile rheumatoid arthritis who did not tolerate or had an inadequate response to methotrexate. Methods Patients 4 to 17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to three months in the initial, open-label part of a multicenter trial. Those who responded to treatment then entered a double-blind study and were randomly assigned to receive either placebo or etanercept for four months or until a flare of the disease occurred. A response was defined as an improvement of 30 percent or more in at least three of six indicators of disease activity, with no more than one indicator worsening by more than 30 percent. Results At the end of the open-label study, 51 of the 69 patients (74 percent) had had responses to etanercept treatment. In the double-blind study, 21 of the 26 patients who received...

Etanercept in Children with Polyarticular Juvenile Rheumatoid Arthritis

Objective. To develop and validate a self- or parent-administered instrument for measuring functional status in children with juvenile rheumatoid arthritis (JRA).

Methods. We adapted the Stanford Health Assessment Questionnaire (HAQ) for use in children ages 1–19 years, by adding several new questions, such that for each functional area, there was at least 1 question relevant to children of all ages. The face validity of the instrument was evaluated by a group of 20 health professionals and parents of 22 healthy children. The questionnaire was then administered to parents of 72 JRA patients (mean age 9.1 years, onset type systemic in 16, polyarticular in 21, pauciarticular in 35).

Results. The instrument showed excellent internal reliability (Cronbach's α = 0.94), with a mean inter-item correlation of 0.6. The convergent validity was demonstrated by strong correlations of the Disability Index (average of scores on all functional areas) with Steinbrocker functional class (Kendall's tau b = 0.77, P 8 years) was 0.84 (n = 29; P 0.9 by paired t-test; Spearman's correlation coefficient = 0.8, P < 0.002).

Conclusion. The Childhood HAQ, which takes less than 10 minutes to complete, is a valid, reliable, and sensitive instrument for measuring functional status in children with JRA.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780371209

Measurement of health status in children with juvenile rheumatoid arthritis

The records of 37 patients with systemic lupus erythematosus (SLE) followed at The Children's Hospital of Philadelphia between 1968 and 1978 were reviewed for evidence of central nervous system (CNS) involvement. Criteria for CNS involvement included evidence of organic brain syndrome, electroencephalographic abnormalities with symptoms referable to CNS, or objective neurologic signs. Sixteen of 37 children had CNS involvement (43%). Thirteen patients had CNS involvement at the onset of SLE. Three patients had late onset CNS manifestations 1 to 2 years after the diagnosis of SLE. The most frequently observed symptoms were headache, behavior disorder, lethargy, diplopia, blurred vision, memory alteration, dizziness, and alteration of consciousness. The most frequently observed neurologic signs were seizures, cranial nerve palsy, ataxia, papilledema, nystagmus, meningitis, tremor, rigidity, cortical blindness, and coma. Neuropsychiatric manifestations included organic brain syndrome, functional psychosis, and personality disorder. Laboratory tests showed elevated cerebrospinal fluid opening pressure and protein, negative cultures, and abnormal electroencephalograms and computerized axial tomography scans. Fourteen of 16 children with CNS manifestations are alive. Thirteen had a mean IQ of 89 by the Wechsler Intelligence Tests. Twelve are in educational programs. One required long-term psychiatric care. A residual neurologic abnormality, a seizure disorder, was present in 3. CNS involvement with SLE in children carries a favorable prognosis.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780241109

Central Nervous System Involvement in Childhood Systemic Lupus Erythematosus

Six patients with reflex sympathetic dystrophy were investigated during the period between 1973 and 1978. Children do not develop the severe, disabling pain nor the patchy osteoporosis (Sudeck's atrophy) which are considered essential features of reflex sympathetic dystrophy in adults. In contrast to the adult variety, reflex sympathetic dystrophy in children is a self-limiting condition which usually responds well to mild analgesics and physical therapy. Frequently it may be necessary to administer the physical therapy in an intensive, inpatient program, both to break the pain-disability cycle and to remove the patient from a stressful family environment that may have initiated or prolonged the syndrome. The use of steroids (dexamethasone) had no appreciable effect on the clinical course in these children.

Reflex sympathetic dystrophy in children.

Older adolescents are in the midst of many life changes related to physical and emotional development, education and career choices, family and peer relationships The presence of a chronic disease adds an additional burden At this stage of development, transfer of care to an adult facility becomes a major challenge for the adolescent, parents, and pediatric and adult care providers This article describes an interdisciplinary transition program from pediatric to adult health care for older adolescents with rheumatic diseases Care is transferred to an internist-rheumatologist who collaborates closely with the pediatric team Scope of the program includes pretransitional assessments and interventions, including education, counseling, and referral around career, postsecondary education, sexuality, and other transitional issues Benefits of and barriers to a structured transition program are discussed

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1790040407

Balu H. Athreya

Papers

Measurement of health status in children with juvenile rheumatoid arthritis

Central Nervous System Involvement in Childhood Systemic Lupus Erythematosus

Reflex sympathetic dystrophy in children.

Adolescents with chronic disease. Transition to adult health care

Clinical characteristics of antiphospholipid antibody syndrome in children