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Biomedical subjects

A M Griffiths

Publications and source records attributed to A M Griffiths.

At least 37 records · Page 2Linked to original sources
PubMed1999

Assessing activity of pediatric Crohn's disease: which index to use?

BACKGROUND & AIMS: The Pediatric Crohn's Disease Activity Index (PCDAI) is a multi-item measure that, in contrast to the adult-derived CDAI, includes linear growth and places less emphasis on subjectively reported symptoms but more on laboratory parameters of intestinal inflammation. This study compared the feasibility, validity, and responsiveness of PCDAI vs. CDAI in the assessment of Crohn's disease activity among pediatric patients. METHODS: Eighty-one children and adolescents with Crohn's disease were studied. A gastroenterologist provided a categorical global assessment of disease activity as quiescent, mild, moderate, or severe after interview and physical examination. CDAI and PCDAI scores were calculated by an independent appraiser. RESULTS: Mean values within each category for CDAI and PCDAI differed significantly between strata. PCDAI values were quiescent, 6.8 +/- 6. 6; mild, 18.7 +/- 7.3; moderate, 38.5 +/- 12.9; and severe, 54.2 +/- 14.0. CDAI values were quiescent, 23.5 +/- 53.6; mild, 96.0 +/- 60. 7; moderate, 184.5 +/- 97.0; and severe, 284.4 +/- 85.8. Individual scores showed less overlap between strata for PCDAI than for CDAI. PCDAI showed better correlation with serum orosomucoid and platelet count, laboratory parameters of inflammation not included in either index. CONCLUSIONS: Both PCDAI and CDAI reflect disease activity in pediatric Crohn's disease. PCDAI is better at discriminating between levels of disease activity.

Adolescent↗
PubMed1999

Development of a quality-of-life index for pediatric inflammatory bowel disease: dealing with differences related to age and IBD type.

BACKGROUND: A child- and adolescent-generated IBD quality-of-life index was designed to be descriptive (to be used to assess the overall impact of IBD on individual patients), and evaluative (to be used as an outcome measure in clinical trials). METHODS: Item-generation and item-reduction interviews with 82 patients with IBD aged 8 to 17 years (61 with Crohn's disease, 21 with ulcerative colitis; 36 girls, 45 boys) generated a list of ways in which their lives were affected by IBD. These issues were incorporated into an item-reduction questionnaire, which was administered to 117 patients (87 Crohn's disease, 30 ulcerative colitis). Patients indicated on a visual analog scale how important an item was to them and how often it bothered them. Mean and median importance-plus-frequency scores for each issue were calculated for the entire group and among patients in subgroups according to age and IBD type. RESULTS: Ulcerative colitis and Crohn's disease affect the lives of children and adolescents differently. Bowel symptoms are more troubling and disabling to patients with ulcerative colitis, whereas systemic symptoms and body image concerns are greater for patients with Crohn's disease. The impact of Crohn's disease on ability to function in school and leisure activities is greater. Worries about future health problems and about the effects of IBD on the family are shared. Crohn's disease and ulcerative colitis trigger emotional responses of unfairness and frustration, but anger and embarrassment are more prevalent in ulcerative colitis. Disparities between age groups are fewer and less marked than those between types of IBD. CONCLUSION: In selection of items to be retained in a pediatric IBD quality-of-life measure, the variation in concerns with disease type must be considered. A single index to assess IBD-related quality of life must include items of major importance to one subgroup of patients, even if not important to all. Alternately, a core of common concerns could be supplemented by disease-specific modules, thereby increasing the content validity of the tool for all patients.

Adolescent↗
PubMed1999

Impact of peritoneal membrane function on long-term clinical outcome in peritoneal dialysis patients.

It is increasingly clear that peritoneal membrane transport status has clinical implications. The role of the peritoneum in dialysis delivery becomes paramount once residual renal function is lost, particularly as the membrane characteristics may change for the worse with time on treatment. These findings have several important implications: Clinicians need to take solute transport characteristics into account as they assess their patients. Adverse effects of high solute transport include reduced ultrafiltration, solute removal (in particular, sodium), and increased peritoneal protein losses. A need exists to replace lost residual renal function, not just with enhanced solute removal, but also with adequate salt and water removal. The interpretation of urea and creatinine clearances in anuric PD patients needs further consideration and validation. Hypoalbuminemia in PD patients will result from the combined effects of high protein losses, over-hydration, comorbidity, and malnutrition.

Biological Transport↗
PubMed1998

Inflammatory bowel disease.

Many nutritional issues are important in the care of children and adolescents with inflammatory bowel disease. No specific dietary toxin or antigen has been identified to have an etiologic role in either ulcerative colitis or Crohn's disease. A possible modulating effect of omega-3 polyunsaturated fatty acids on intestinal inflammation is being investigated. Most prevalent among the nutritional consequences of inflammatory bowel disease is weight loss, for which inadequate caloric intake is primarily responsible. Impairment of linear growth and associated delay in pubertal development commonly complicate childhood Crohn's disease. The two major etiologic factors are chronic undernutrition and direct effects of inflammatory mediators secreted from the inflamed gut. Recent studies have incriminated interleukin-6. Treatment of intestinal inflammation and provision of adequate nutrition are of paramount importance in preventing or remedying growth impairment. Exclusive enteral nutrition using formulated food is efficacious primary therapy of active Crohn's disease, although the mode of action is poorly understood.

Adolescent↗
PubMed1998

Crohn's disease in adolescents.

The clinical features of Crohn's disease manifest during adolescence are varied as in adults. The potential complication of growth impairment and concomitant delay in pubertal development is unique to this population. Cytokines released from the inflamed bowel and chronic nutritional insufficiency are the major factors in the pathophysiology of growth inhibition. Hence reduction of intestinal inflammation and consistent provision of adequate nutrition are of paramount importance in management. Drug treatment mirrors that of adults; few specifically paediatric clinical trials have been conducted. Enteral nutrition is an important therapeutic alternative for young patients. There is evidence that it constitutes both a primary therapy of inflammation and a means of providing the calories needed for growth. In the setting of extensive disease, dependency on corticosteroids should be minimized through judicious administration of immunosuppressive drugs. For an adolescent with localized stenotic disease, optimal management includes a timely referral for intestinal resection as a means of providing an asymptomatic interval during which growth and pubertal development can normalize.

Adolescent↗
PubMed1998

Ketotifen therapy for acute ulcerative colitis in children: a pilot study.

Eosinophils contribute to the inflammatory process in a variety of chronic inflammatory bowel diseases. Ketotifen is beneficial in experimental models of colitis and in patients with eosinophilic gastroenteritis. Therefore, we investigated the efficacy of ketotifen therapy for the treatment of active ulcerative colitis. Children with newly or previously diagnosed ulcerative colitis with mild-moderate disease activity were treated with ketotifen at a dosage of 4 mg daily for eight weeks. Efficacy was determined by a physician disease severity index and by endoscopic and histologic examinations. Ten patients were enrolled. Symptoms improved in four patients and resolved completely in one patient. There was endoscopic improvement in three patients and histologic improvement in one. Increased eosinophils on rectal biopsy at entry were present in two of the responders. Five patients withdrew due to a lack of symptomatic improvement. No adverse events were identified. Low-dose ketotifen offers a limited therapeutic advantage in active ulcerative colitis that may be enhanced in the subgroup of patients with a high eosinophil count in the colonic mucosa. Further study of therapeutic efficacy with increased dosages of the mast cell stabilizer for acute and maintenance therapy is warranted.

Child↗
PubMed1998

What really happens to people on long-term peritoneal dialysis?

BACKGROUND: Several risk factors for patients treated with peritoneal dialysis (PD) have now been identified. These include age, comorbid disease, nutritional status, loss of residual renal function (RRF) and high peritoneal solute transport. This is not the same, however, as knowing what actually happens to these patients, particularly in the long-term. The purpose of this review was to give as complete a description as is currently possible of the long-term PD patient. METHODS: The literature was surveyed for publications that provide longitudinal cohort data of either selected or unselected patient groups. Detailed data from the Stoke PD Study is presented in the context of these studies. Three principle aspects of what really happens to patients were considered: (1) death, both cause and mode of death; (2) technique failure, with reference to peritoneal function and how the cause of technique failure related to patient survival; and (3) evolution of clinically relevant parameters of patients on PD, such as nutrition and peritoneal function. RESULTS: Sudden death and debilitation were the predominant modes of death, with sepsis playing a contributory role. Debilitation was important regardless of co-existent comorbid disease, and time to death was not influenced by the mode of death. Predominant causes for technique failure remain peritonitis and ultrafiltration, the latter becoming more important with time on treatment. Technical failure is associated with poorer survival, particularly when due to multiple peritonitis or failure to cope with treatment. Cox regression demonstrated that whereas low albumin, loss of RRF and high solute transport predicted patient death, only high solute transport predicted technique failure. Longitudinal changes over the first five years of treatment included loss of RRF, increasing solute transport and following an initial improvement in nutritional state, a decline after two years. Patients surviving long-term PD (at least five years, N = 25) were characterized by prolonged RRF, maintained nutrition and lower solute transport in the medium term. CONCLUSIONS: Several studies of long-term PD in the literature now complement each other in providing a picture of what really happens to PD patients. The links between loss of solute clearance and poor peritoneal ultrafiltration combining to exacerbate sudden or debilitated death and technique failure are emerging. For PD to be successful as a long-term therapy, strategies that maintain nutrition and preserve peritoneal membrane function must be developed.

Cause of Death↗
PubMed1997

Keeping an eye on Crohn's disease: orbital myositis as the presenting symptom.

Episodic periorbital swelling due to presumed orbital inflammation and myositis caused intermittent apparent proptosis and was the presenting symptom of ileocecal Crohn's disease (CD) in a teenage female with a family history of autoimmune disorders and CD. Orbital myositis, a very rare extraintestinal manifestation of inflammatory bowel disease (IBD), likely represents a process of impaired immunoregulation related to the underlying intestinal inflammation. This rare manifestation of IBD simulates the more commonly encountered thyroid orbitopathy (ophthalmopathy), but IBD should be considered if all thyroid tests are negative. It is important to recognize that orbital myositis may be an extraintestinal manifestation of Crohn's disease so that the diagnosis can be made and appropriate therapy commenced.

Autoimmune Diseases↗
PubMed1995

Meta-analysis of enteral nutrition as a primary treatment of active Crohn's disease.

BACKGROUND/AIMS: The efficacy of enteral nutrition as primary therapy of active Crohn's disease is controversial. The aim of the study was to compare by meta-analysis the likelihood of clinical response to liquid diet therapy vs. corticosteroids and to assess the importance of formula composition to efficacy. METHODS: Randomized controlled trials comparing exclusive enteral nutrition with corticosteroids and elemental with nonelemental formulas were identified through a combination of computerized and hand-searching techniques. Rates of clinical remission of active Crohn's disease, based on the intention-to-treat principle, were extracted from the studies by two independent reviewers. Odds ratios for likelihood of clinical response were calculated. RESULTS: In eight trials comprising 413 patients, enteral nutrition was inferior to corticosteroids (pooled odds ratio, 0.35; 95% confidence interval, 0.23-0.53). In five trials comprising 134 patients, there was no difference in the efficacy of elemental versus nonelemental formulas (pooled odds ratio, 0.87; 95% confidence interval, 0.41-1.83). CONCLUSIONS: Corticosteroids are more effective than enteral nutrition in the treatment of active Crohn's disease. Limited sample size precludes definitive conclusions about the importance of formula composition in the efficacy of enteral nutrition; however, data analyzed in this study do not support an advantage to elemental feedings compared with a polymeric formulation.

Adrenal Cortex Hormones↗
PubMed1995

Acute cytomegalovirus infection in a child with Ménétrier's disease.

The cause of Ménétrier's disease is unknown, although allergic, autoimmune, and infectious, particularly viral, causes have been postulated. This case report describes a 3-year-old child with Ménétrier's disease in whom evidence of acute cytomegalovirus (CMV) infection was found. To our knowledge, this is the first case with evidence of acute infection, indicated by the presence of CMV-specific immunoglobulin M antibody in the acute serum as well as a seroconversion to CMV. CMV was also found in a gastric mucosal biopsy specimen using monoclonal antibodies to the early antigen of CMV.

Acute Disease↗
PubMed1995

Levels of peptidoleukotriene E4 are elevated in active Crohn's disease.

Proinflammatory mediators, including leukotriene (LT) B4, are elevated in the intestinal mucosa in active chronic inflammatory bowel diseases (IBD). LTE4 is the major peptidoleukotriene metabolite and it is stable in urine. The aim of this study was to measure LTE4 levels in the urine of 27 children with Crohn's disease and 27 control subjects including 12 children with functional recurrent abdominal pain and 15 unaffected siblings of IBD patients. LTE4 levels were measured in urine using high-performance liquid chromatography separation and radioimmunoassay with specific antibody. The Pediatric Crohn's Disease Activity Index and physician global assessment were used to categorize patient groups. C-reactive protein, orosomucoid, and erythrocyte sedimentation rate were employed as laboratory markers of mucosal inflammation. Urinary LTE4 levels were elevated in the 13 children with active Crohn's disease (160.5 +/- 59.4 pg/ml; mean +/- SEM) compared with both levels in the 14 patients with inactive disease (67.1 +/- 18.1 pg/ml; p < 0.05) and controls (45.0 +/- 10.9 pg/ml; p < 0.05). We conclude that measurement of urinary LTE4 is a useful test for monitoring the activation of peptidoleukotrienes in patients with Crohn's disease. It provides a noninvasive, objective adjunct for assessment of disease activity and could be employed in future trials examining the role of the leukotriene inhibitors in the medical therapy of IBD.

Acute Disease↗
PubMed1995

Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis.

The clinical presentation and outcome of 32 children with primary sclerosing cholangitis (PSC) are reviewed, the largest North American series. The majority of patients were diagnosed in their second decade (median age: 13 years). Four children presented before the age of 2 years, but none in the neonatal period. Seventeen patients had inflammatory bowel disease (IBD), all with colitis, 14 ulcerative colitis, and 3 Crohn's disease. Eight patients presented with chronic liver disease before clinical onset of IBD. Only 8 of 32 patients were jaundiced at presentation. Fifteen of 32 had a normal serum alkaline phosphatase (ALP) level at presentation. Nine children presented with features similar to those of autoimmune hepatitis. Cholangiography was performed in all cases and classified by a scoring system specifically developed for pediatric patients. Intrahepatic disease predominated; in only three cases a common bile duct stricture was identified requiring stenting. Findings on the initial liver biopsy were classified according to Ludwig's criteria for staging PSC: there were 15 biopsies in stages 1 to 2 and 17 biopsies stages 3 to 4. HLA class I and II antigens were determined in 27 patients. An increased incidence of HLA B8 and DR2(15) but not DRw52a (DRB3*0101) was found. Anti-neutrophil cytoplasmic antibody (ANCA) was positive in 10 of 24 patients tested. Survival analysis indicated that a later age at presentation, splenomegaly, and prolonged prothrombin time (PT) at presentation were significant contributors to the prediction of poor outcome (i.e., death or listing for transplantation). Liver transplantation was successfully performed in seven children. Physicians must maintain a high index of suspicion of PSC in any child or young adult presenting with chronic liver disease, especially in the presence of IBD, even with a normal serum alkaline phosphatase level.

Adolescent↗