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A M Griffiths

Publications and source records attributed to A M Griffiths.

12 recordsLinked to original sources
PubMed1992

Relationship of common laboratory parameters to the activity of Crohn's disease in children.

The Pediatric Crohn's Disease Activity Index (PCDAI) has been proposed as a simple instrument to aid in the classification of patients by disease severity. The PCDAI includes subjective patient reporting of symptoms, physical examination, nutritional parameters, and several common laboratory tests (hematocrit, erythrocyte sedimentation rate, albumin). In this report we examine the relationship of each of the laboratory parameters to the PCDAI, as well as to a modified Harvey-Bradshaw Index score and physician global assessment of disease activity. Data were gathered from the clinical and laboratory observations from 133 children and adolescents at 12 pediatric gastroenterology centers in North America. A statistically significant relationship (p less than 0.05) was noted between each of the laboratory tests and the PCDAI for patients with either disease limited to the small bowel or in those with colonic involvement. For patients with disease limited to the small bowel, a statistically significant (p less than 0.05) relationship was also noted between the three laboratory parameters and the modified Harvey-Bradshaw Index and global assessment. For patients with large-bowel involvement, the erythrocyte sedimentation rate was statistically related to the modified Harvey-Bradshaw Index and global assessment (p less than 0.01), as was hematocrit to global assessment (p less than 0.01). Although the laboratory parameters used in the PCDAI appear to generally reflect disease activity in most patients, no single laboratory test is adequate to reflect disease activity in all patients. Future work will need to identify additional laboratory measures to reflect the inflammatory process and serve as important adjuncts in the assessment of disease activity.

Adolescent↗
PubMed1991

Neutrophil dysfunction in glycogen storage disease Ib: association with Crohn's-like colitis.

Two cases of patients with Crohn's-like colitis and glycogen storage disease Ib have been reported previously. In the current report, chronic inflammatory bowel disease that developed in another adolescent with this glycogenosis is described, thereby corroborating the association. The neutrophil dysfunction observed in glycogen storage disease Ib is the most likely predisposing factor. Neutrophil function was investigated in our patient in an attempt to shed light on the pathogenesis of his intestinal inflammation. The patient displayed reduced neutrophil chemotaxis to zymosan-activated serum, N-formyl-methionine-phenylalanine, and Escherichia coli bacteria-derived factor and reduced intracellular killing of Staphylococcus aureus 502A. Others have found this defective bacteriocidal activity to be caused by impaired oxidative metabolism. The recent recognition of chronic inflammatory bowel disease in glycogen storage disease Ib, as well as in chronic granulomatous disease, suggests that further study of respiratory burst activity of neutrophils in Crohn's disease is warranted.

Adolescent↗
PubMed1991

Perianal complications of pediatric Crohn's disease.

The management of perianal disease (PD) in children with Crohn's disease was reviewed. Of 325 patients (184 boys), 200 (62%) developed PD. The mean age at diagnosis of Crohn's disease was 11.2 years (range, 5 to 17 years). Skin tags were present in 114 (35%) patients, fissures in 165 (51%), fistulas in 41 (15%), and perirectal abscesses in 47 (13%). One hundred fifty-three patients had PD as one of the first symptoms; 71 of these had complete remission of PD and the remaining 82 had chronic symptoms. Forty-two patients were initially free of PD, only to develop it later. PD occurred in 50% of patients with gastroduodenal Crohn's disease, 57% with jejunal, 68% with ileal, 64% with ileocecal, 60% with ileocolic, and 51% with colonic. Local minor operation was necessary in 38 (12%) patients, fistulotomy in 12, and abscess drainage in 26. Four patients required either intestinal resection and/or enterostomy for progressive PD. Fifty-three patients received metronidazole, with amelioration in 38. It is concluded that PD is a common complication of Crohn's disease in children and adolescents. Its presentation may antedate that of the primary disease. Most PD follows a benign course. There is a limited role for operation, but a need for meticulous perineal care and a potential benefit with metronidazole therapy. We advocate conservatism in the management of perianal complications of Crohn's disease in pediatric patients.

Abscess↗
PubMed1991

Factors influencing postoperative recurrence of Crohn's disease in childhood.

We have reviewed the outcome of all patients undergoing their first intestinal resection for Crohn's disease at this hospital between 1970 and 1987. Recurrence rates, defined by recurrent intestinal symptoms and radiological confirmation of mucosal disease, were calculated using survival analysis. Age, sex, anatomical location of disease, indication for surgery, preoperative duration of symptomatic disease, use of preoperative bowel rest, and pathological features of the resected bowel were analysed individually and jointly as potential risk factors influencing postoperative recurrence of disease. Eighty two patients (age, mean (SD) 14.8 (2.5) years) underwent intestinal resection and were followed postoperatively for a minimum of one year (mean 5.3 (3.3) years). Anatomical location of disease, indication for surgery, and preoperative duration of symptomatic disease were the only factors that significantly influenced the duration of the recurrence free interval. Patients with diffuse ileocolonic inflammation experienced earlier recurrence (50% at one year) than children with predominantly small bowel disease (50% recurrence at five years, p less than 0.0001). Failure of medical therapy independent of disease location as the sole indication for surgery was associated with an earlier relapse than when surgery was performed for a specific intestinal complication such as abscess or obstruction (p less than 0.003). Patients undergoing resection within one year of onset of symptoms experienced delayed recrudescence of active disease (30% recurrence by eight years) compared with patients whose preoperative duration of symptomatic disease was longer (50% recurrence by four years when preoperative duration of disease was one to four years and 50% by three years when disease had been present greater than four years preoperatively, p = 0.03). The mean height velocity of patients with growth potential increased from 2.4 (2.3) cm per year preoperatively to 8.1 (3.4) cm per year in the first postoperative year (p=0.0001). These results support an early approach to surgery in the management of ileal Crohn's disease with or without caecal or right colonic involvement, especially when complicated by persistent growth failure. The higher recurrence rates in more diffuse ileocolonic disease emphasise the need for alternative treatment strategies in these children.

Adolescent↗
PubMed1991

Development and validation of a pediatric Crohn's disease activity index.

Clinical and laboratory observations of 133 children and adolescents with Crohn's disease were used to validate an index of severity of illness previously developed by a group of senior pediatric gastroenterologists at a research forum in April 1990. This pediatric Crohn's disease activity index (PCDAI) included (a) subjective reporting of the degree of abdominal pain, stool pattern, and general well-being; (b) presence of extraintestinal manifestations, such as fever, arthritis, rash, and uveitis; (c) physical examination findings; (d) weight and height; and (e) hematocrit, erythrocyte sedimentation rate, and serum albumin. Independent evaluation of each patient by two physician-observers was performed at the time of a visit, and each physician completed a PCDAI index and a modified Harvey-Bradshaw index and made a "global assessment" of disease activity as none, mild, moderate, or severe. Excellent interobserver agreement was noted for the PCDAI, modified Harvey-Bradshaw index, and global assessment. There was a strong correlation between global assessment and both the PCDAI or modified Harvey-Bradshaw. Increasing PCDAI scores were noted with increasing disease severity, and significant differences in scores were noted between the severity groups. We propose that the PCDAI could be used in multicenter projects to facilitate patient stratification by disease severity and that longitudinal PCDAI scores might provide a numerical measure of response to therapeutic regimens.

Adolescent↗
PubMed1990

Synovial fluid fibronectin fragments: no evidence for a mitogenic effect on fibroblasts.

Fragments of bovine plasma fibronectin produced by cathepsin D digestion are reportedly mitogenic for hamster fibroblasts. Rheumatoid arthritis synovial fluid contains many fibronectin fragments, which may contribute to the proliferation of synovial cells. We have therefore investigated the potential of fibronectin fragments to stimulate proliferation of synovial fibroblast-like cells using human material. Affinity-purified human plasma and synovial fluid fibronectin was digested with cathepsin D at pH 3.5 for 0-18 h and proteolysis stopped with pepstatin. A variety of fragments were produced ranging from 50 to 200 kDa when analysed by SDS-PAGE. The proliferative activity of various test preparations was studied using quiescent human skin and synovial fibroblasts. Tests were applied for 24 h to 10(4) cells and DNA synthesis measured by tritiated thymidine incorporation. Both undigested and peptides of fibronectin consistently failed to stimulate DNA synthesis in fibroblasts at all concentrations tested, compared with a phosphate-buffered saline control. This was in marked contrast to human synovial fluid from either rheumatoid arthritis or osteoarthritis patients, which stimulated DNA synthesis in the same system (P less than 0.01). Therefore, our data do not confirm the findings of previous studies in which animal materials were used. We can find no evidence that fibronectin fragments play a role in stimulating synovial proliferation in inflammatory arthritis.

Arthritis, Rheumatoid↗
PubMed1990

Pathological features of multiple endocrine neoplasia type IIb in childhood.

The features of two patients with multiple endocrine neoplasia type IIb are described. Patient 1, a 9-year-old boy with marfanoid features, presented with chronic constipation and failure to thrive since infancy. Patient 2, a 12-year-old boy with marfanoid features, presented with a five-year history of persistent cervical lymphadenopathy. In patient 1, the myenteric and submucosal nerve plexuses at all levels of the small and large intestines were comprised of diffusely disorganized, hyperplastic, mature ganglion cells and nonmyelinated nerve fibers. Nerve plexus dissection with morphometric analysis showed marked thickening of the myenteric plexus with a quantitative increase in neural tissue. Patient 2 had a submucosal neuroma of the tongue. Both patients had occult medullary thyroid carcinoma, and patient 2 had cervical lymph node metastases. Both neoplasms showed positive staining for cytokeratin, carcinoembryonic antigen, calcitonin, bombesin, chromogranin, serotonin, and Leu 7. Electron microscopy showed membrane-bound, intermediate-sized, dense-core neurosecretory granules in tumor cells. In patient 2, calcitonin-positive amyloid was present with localization of calcitonin by immunoelectron microscopy to cytoplasmic secretory granules and to extracellular amyloid fibrils. These cases illustrate the potential for missed or delayed diagnosis in multiple endocrine neoplasia syndromes.

Carcinoma↗
PubMed1989

Fragmented fibronectin and other synovial fluid proteins in chronic arthritis: their relation to immune complexes.

Fibronectin, an opsonic glycoprotein has been shown to exist in fragmented forms in serum and synovial fluid. Some fragments in synovial fluid appear to be polyethylene glycol (PEG) precipitable, suggesting incorporation into immune complexes (IC). PEG precipitation, SDS-PAGE and immunoblotting were used to determine whether PEG precipitable fragments are real or artefactual. Disease specificity of fragmentation and IC incorporation of fibronectin and other proteins were also studied using these techniques. PEG precipitable fragments do not appear to be artefactual, although some fibronectin fragments are cryoprecipitable. Protein fragments showed similar distributions in whole serum and synovial fluid, disease specific differences being confined to PEG precipitates. Rheumatoid arthritis (RA) synovial fluid PEG precipitates displayed the greatest array of fragmented immunoglobulins and fibronectin. No PEG precipitates contained albumin fragments. Protein fragments in IC may impair their effective removal from RA joints. Accumulated IC could lead to tissue damage via complement activation.

Adult↗
PubMed1989

Clinical features of gastroduodenal Crohn's disease in adolescents.

Ten cases of gastroduodenal inflammation were diagnosed by endoscopy among a series of 196 children with evidence of Crohn's disease involving other regions of the intestinal tract. Endoscopic and histologic confirmation of upper gastrointestinal tract involvement was performed only in those cases with suggestive symptoms. The mean age at presentation in the 10 cases with gastroduodenal inflammation was 14.6 +/- 1.9 (+/- SD) years, with involvement identified at the time of initial diagnosis of Crohn's disease in five of the 10. Eight of 10 cases occurred in boys. The major presenting symptoms were weight loss in five cases, epigastric pain in three, and recurrent vomiting in two. Hematemesis and melena occurred in only one of the 10 cases. Endoscopic and histological evidence of mucosal inflammation was seen in all 10 cases. Three of 10 cases had noncaseating granuloma present in biopsies of the stomach or duodenum. Two cases also had endoscopic and histological evidence of esophageal involvement. All cases were initially treated with oral corticosteroids, and in each instance a good clinical response was noted. Sucralfate (n = 1), 6-mercaptopurine (n = 1), and H2 receptor antagonists (n = 3) were used as adjunct therapy. After follow-up for 2.7 years (range, 0.5-5.5 years), none of the 10 cases required surgical intervention. Therefore, at least in the short-term, the outlook for adolescents with gastroduodenal Crohn's disease appears to be good and their medical management need not differ from those patients with Crohn's disease involving only more distal portions of the small intestine.

Adolescent↗