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Biomedical subjects

C A Wallace

Publications and source records attributed to C A Wallace.

At least 37 records · Page 2Linked to original sources
PubMed1998

Endothelin interactions with brain dopamine systems.

We examined the interactions of endothelin (ET) with dopaminergic systems in rat brain. Using HPLC and radioimmunoassay, we found that striatum contained the highest levels of predominantly ET-1, whereas highest levels of predominantly ET-3 were found in the pituitary. Dopamine depletion in the striatum did not change the levels of immunoreactive ET, even though we have previously found a decrease in the density of ET receptors. In a comparison of spontaneously hypertensive rats (SHR) with Wistar-Kyoto (WKY) rats, ET levels were lower in cerebellum and medulla, with no difference in striatum or in other brain areas. In conclusion, ET is present in high levels in striatum, but these levels are not affected by dopamine depletion or in SHR.

Animals↗
PubMed1998

Primary caregivers of persons with brain injury: life change 1 year after injury.

The impact of a traumatic brain injury on the family of the injured person is just beginning to be explored. In the current study, 61 primary caregivers were contacted at 1 year following injury. They completed the Relative and Friend Support Index, Social Support Index, Trauma Complaints List and the Life Change Question. The majority of caregivers indicated at least mild negative life change following the brain injury. Greater social support was correlated with less life change and greater injury severity was correlated with negative life change. Neither of these relationships was found to be significant at the 0.05 level. A significant positive correlation was found between caregivers' perception of deficits and the degree of negative life change. Perceived deficits accounted for the greatest amount of variance in life change followed by relative and friend support when all variables were entered into a stepwise regression. Further analyses indicated that the most significant factor of the Trauma Complaints List in predicting life change may be problems with cognition, which accounted for a significant amount of the variance in life change. Implications for counselling and further research regarding caregivers of persons with brain injury are discussed.

Adolescent↗
PubMed1997

Trial of intravenous pulse cyclophosphamide and methylprednisolone in the treatment of severe systemic-onset juvenile rheumatoid arthritis.

OBJECTIVE: Not uncommonly, some children with systemic-onset juvenile rheumatoid arthritis (JRA) have persistently active disease with joint destruction and profound growth delay despite maximum treatment with known medications. Based on previous observations of improvement in synovitis following intravenous (I.V.) cyclophosphamide (CYC) and methylprednisolone (MP) treatments, a group of children with severe systemic-onset JRA was treated in an attempt to control active synovitis and to allow tapering of corticosteroids. METHODS: Four patients with systemic-onset JRA were continued on a daily regimen of nonsteroidal antiinflammatory agents and prednisone, with a weekly subcutaneous dose of methotrexate (1 mg/kg). In addition, 1 patient continued receiving sulfasalazine and 1 patient remained on a regimen of sulfasalazine and hydroxychloroquine. Patients received 6-10 monthly treatments of I.V. CYC (500-1,000 mg/m2) and MP (30 mg/kg; 1 gm maximum) accompanied by I.V. mesna and large amounts of I.V. fluids. Subsequent treatments were given once every 2-3 months. RESULTS: After 12-20 I.V. pulses of CYC, all patients showed improvement, and 3 achieved remission of disease. All were able to discontinue corticosteroid use and all had an increase in linear growth. CONCLUSION: Monthly I.V. pulse CYC treatments can be useful to control disease in selected children with severe, destructive JRA.

Adrenal Cortex Hormones↗
PubMed1997

Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies: I. Physician, parent, and patient global assessments. Juvenile Dermatomyositis Disease Activity Collaborative Study Group.

OBJECTIVE: To determine the reliability, content validity, and responsiveness of physician global assessments of disease activity and damage in the juvenile idiopathic inflammatory myopathies (IIM), and to investigate concordance among physician, parent, and patient global ratings. METHODS: Sixteen pediatric rheumatologists rated 10 juvenile IIM paper patient cases for global disease activity and damage, and assessed the importance of 51 clinical and laboratory parameters in formulating their global assessments. Then, 117 juvenile IIM patients were enrolled in a protocol to examine the relationship between Likert and visual analog scale global assessments, their sensitivity to change, and the comparability of physician, parent, and patient global ratings. RESULTS: Pediatric rheumatologists demonstrated excellent interrater reliability in their global assessments of juvenile IIM disease activity and damage (97.7% and 94.7% agreement among raters, respectively), and agreed on a core set of clinical parameters in formulating their judgments. Likert scale ratings correlated with those on a visual analog scale, and both were comparable in responsiveness (standardized response means -0.56 for disease activity, 0.02 [Likert] and 0.14 [visual analog] for damage, measured over 8 months). Parent global ratings of disease activity correlated with physician assessments, but were not colinear (Spearman's correlation [r] = 0.41-0.45). Patient global disease activity assessments correlated with those done by parents (r = 0.57-0.84) and physicians (r = 0.37-0.63), but demonstrated less responsiveness (standardized response means -0.21 and -0.12, respectively, over 8 months). CONCLUSION: Physician global assessments of juvenile IIM disease activity and damage demonstrated high interrater reliability and were shown to be comprehensive measures. Both physician and parent disease activity assessments should be considered valuable as quantitative measures for evaluating therapeutic responses in juvenile IIM patients.

Arthritis, Juvenile↗
PubMed1997

Quantitative trait loci for cellular defects in glucose and fatty acid metabolism in hypertensive rats.

Coronary heart disease, hypertension, non-insulin-dependent diabetes and obesity are major causes of ill health in industrial societies. Disturbances of carbohydrate and lipid metabolism are a common feature of these disorders. The bases for these disturbances and their roles in disease pathogenesis are poorly understood. The spontaneously hypertensive rat (SHR), a widely used animal model of essential hypertension, has a global defect in insulin action on glucose metabolism and shows reduced catecholamine action on lipolysis in fat cells. In our study we used cellular defects in carbohydrate and lipid metabolism to dissect the genetics of defective insulin and catecholamine action in the SHR strain. In a genome screen for loci linked to insulin and catecholamine action, we identified two quantitative trait loci (QTLs) for defective insulin action, on chromosome 4 and 12. We found that the major (and perhaps only) genetic determinant of defective control of lipolysis in SHR maps to the same region of chromosome 4. These linkage results were ascertained in at least two independent crosses. As the SHR strain manifests many of the defining features of human metabolic Syndrome X, in which hypertension associates with insulin resistance, dyslipidaemia and abdominal obesity, the identification of genes for defective insulin and catecholamine action in SHR may facilitate gene identification in this syndrome and in related human conditions, such as type-2 diabetes and familial combined hyperlipidaemia.

Animals↗
PubMed1996

Pediatric rheumatology in adult rheumatology practices in Washington state.

OBJECTIVE: To determine both the extent to which adult rheumatologists treat children and their level of comfort in doing so. METHODS: A questionnaire was sent to all 77 physicians in the state of Washington who were listed as adult rheumatologists in the American College of Rheumatology (ACR) directory. RESULTS: Sixty-six questionnaires (86%) were returned; 50 were identified as being from private-practicing adult rheumatologists and were the focus of this study. Sixty-two percent of the respondents reported that they care for children; predictors included increased exposure to pediatric rheumatology during fellowship (P = 0.003), increased distance from Seattle (P = 0.001), and listing oneself in the ACR directory as treating children (P = 0.03). Most respondents reported feeling discomfort in treating children younger than 6 years of age, treating Kawasaki disease, and treating polyarteritis nodosa, but most reported feeling comfortable treating children with chronic arthritides. Impediments to referring to a pediatric rheumatologist included distance (median distance 35 miles), convenience for the family, personal preference, and experience in caring for children. Twenty-nine percent reported difficulties referring to a pediatric rheumatologist outside of one's managed care plan. Adult rheumatologists expressed interest in continuing medical education dealing with pediatric rheumatology, preferably with a lecture format in their home communities. CONCLUSION: A significant number of adult rheumatologists care for children. Pediatric rheumatologists should provide both educational and consultative support for these adult rheumatologist colleagues.

Adult↗
PubMed1995

Reverse, innervated latissimus dorsi flap reconstruction of congenital diaphragmatic absence.

Children with congenital diaphragmatic absence have experienced a high mortality rate regardless of early intervention due to regression to fetal circulation patterns. Advances in neonatal care, particularly extracorporeal membrane oxygenation, have led to the survival of children who previously would not have lived. With growth, the Gore-Tex patch used for emergency repair in severe cases pulls away from the rib periosteum as a result of the expansile growth of the chest wall and the indistensibility of the patch. Recurrent herniation of abdominal contents ensues, slowly restricting pulmonary function and development. When pulmonary function is significantly impaired, we perform a reverse latissimus dorsi flap reconstruction with anastomosis of the thoracodorsal nerve to the phrenic nerve. Our series includes five children aged 5 to 11 months. Follow-up ranges from 22 to 50 months. Three children have proven physiologic neodiaphragmatic motion. The other two are doing well with stable absence of paradoxical motion. There have been no complications. Long-term follow-up will be required to determine their eventual fate. The prognosis is encouraging.

Diaphragm↗
PubMed1993

Pilot investigation of naproxen/methotrexate interaction in patients with juvenile rheumatoid arthritis.

OBJECTIVE: To investigate the potential interaction of naproxen and methotrexate (MTX) in children with juvenile rheumatoid arthritis (JRA). METHODS: Nine children with JRA served as their own control taking their usual doses of MTX (0.22-1.02 mg/kg/week) and naproxen (14.6-18.8 mg/kg/day) separately and in combination. RESULTS: MTX affected a > or = 30% change in naproxen kinetics in 6/8 patients, while naproxen altered MTX kinetics by > or = 30% in 4/9 patients. CONCLUSION: MTX can alter nonsteroidal antiinflammatory drug (NSAID) kinetics in children with JRA and NSAID can alter MTX kinetics. NSAID toxicity should be considered when assessing adverse reactions in patients receiving the combination treatment of MTX and NSAID:

Adolescent↗
PubMed1993

Predicting remission in juvenile rheumatoid arthritis with methotrexate treatment.

Forty-nine children with a polyarticular course of juvenile rheumatoid arthritis treated with methotrexate (MTX) for at least one year were analyzed to identify clinical characteristics that would predict remission of arthritis after MTX treatment. Twenty-two children (45%) had remission of arthritis after a mean of 13.6 months of treatment and did not differ from the 27 with persistently active arthritis regarding years of disease before starting MTX, age starting MTX, maximum MTX dose, disease onset type, presence of radiographic joint destruction, concomitant treatment with hydroxychloroquine, sulfasalazine or prednisone, or presence of rheumatoid factor or antinuclear antibodies. Higher dose MTX, earlier treatment, genetic markers, and a standardized route of therapy may yield important information in future studies.

Arthritis, Juvenile↗
PubMed1992

Preliminary report of higher dose methotrexate treatment in juvenile rheumatoid arthritis.

Methotrexate (MTX) is widely used to treat juvenile rheumatoid arthritis (JRA). Although most patients respond to lower doses (0.15-0.5 mg/kg/wk), some patients have required higher doses of MTX to control their arthritis. Thirteen children were treated with MTX 0.82-1.1 mg/kg/wk for 2-26 months. Although all children initially responded (> 50% improvement in joint index, erythrocyte sedimentation rate, morning stiffness and global evaluation), 4 patients discontinued treatment because of side effects or lack of prolonged efficacy. Five patients have continued taking higher dose MTX for 4-26 months, while 4 other patients have been able to decrease their MTX dose and maintain improvement. Twenty-four hour MTX levels were done on all patients at initiation of higher dose MTX and all cleared MTX well. Our report suggests that MTX in doses of 0.82-1.1 mg/kg/wk can successfully treat active synovitis in some children with severe JRA with few short term toxicities. Longterm use at these doses has not been studied and thus its safety is not known.

Adolescent↗
PubMed1992

Dismantling the pyramid.

The suggestion is heard, with increasing frequency, that the therapeutic pyramid be dismantled and that medical management be reordered to treat juvenile rheumatoid arthritis as early and as decisively as possible to induce prompt remission of disease, thereby preserving function and the quality of life. We scrutinize paradigms that guide our treatment strategies, review current practices, update data derived from those practices, and propose reassessment for treatment in the 1990s.

Anti-Inflammatory Agents↗
PubMed1991

Juvenile rheumatoid arthritis: outcome and treatment for the 1990s.

There has been much discontent with the hazards and the uncertain responses of patients with juvenile rheumatoid arthritis (JRA) to time-honored modalities of management. The treatment of JRA is often thought of as a pyramid with the base formed by nonsteroidal anti-inflammatory drugs, patient and family education, physical therapy, occupational therapy, and family support. Mechanisms of human disease have begun to open the gates to understanding the why and when of connective tissue diseases; they also offer the prospect of direct therapeutic intervention. In this article, the authors scrutinize the paradigms that guide our treatment strategies, review current practices, update data derived from those practices, and propose reassessment of therapy in the 1990s.

Arthritis, Juvenile↗
PubMed1991

Psychosomatic musculoskeletal pain in childhood: clinical and psychological analyses of 100 children.

The clinical and psychological findings on 100 children with psychosomatic musculoskeletal pain seen at a major pediatric rheumatology referral center are reported. Most (76%) were female, median age was 13 years, and median duration of symptoms was 1 year. Multiple painful sites were common (66%). The pain was constant (63%) or intermittent (37%); 45% had hyperesthesia, and almost all maintained a cheerful affect when complaining of severe pain. Two predominant abnormal family milieu were seen. One was cohesive, stable, and organized, but intolerant of separation and individuation. The other was chaotic, emotionally unsupportive, with high levels of conflict. Members of the cohesive family type reported significantly less distress than members of chaotic families. Enmeshment between mother and child was common in both family types. Although frequently viewed as bright, most of these children had normal intelligence, and some had unrecognized academic difficulty. These children, compared with those with arthritis, had a significantly lower global well-being score. Clinical depression was unusual (11%). Most (97%) responded favorably to intensive physical and occupational therapy along with individual or family psychotherapy; 78% become symptom free or fully functional. Children with these signs and symptoms should have full psychological evaluations and respond well to treatment directed toward decreasing pain and restoring function.

Adolescent↗