Methotrexate treatment in pediatric Crohn disease patients intolerant or resistant to purine analogues.

BACKGROUND: Immunomodulatory drugs play a major role in maintaining remission and steroid sparing in children with Crohn disease. Although thiopurine agents are commonly used, unresponsiveness or intolerance to these drugs is common. The efficacy of methotrexate in maintenance of remission has been shown in adult Crohn disease; however, pediatric data are limited. Our goal was to evaluate the efficacy and safety of methotrexate in induction and maintenance of clinical remission in children with active Crohn disease who failed thiopurine treatment. PATIENTS AND METHODS: In a retrospective multicenter study, efficacy of methotrexate in inducing and maintaining remission or response was assessed by Harvey-Bradshaw activity index, paediatric Crohn disease activity index and steroid use, in 25 children with Crohn disease, refractory or intolerant to thiopurine analogues. RESULTS: Crohn disease was diagnosed at a mean age of 11.1 +/- 3.1 years and methotrexate was initiated at age 14.5 +/- 3.1 years. The median methotrexate dose was 12.5 mg/m2. Remission was achieved in 16 patients (64%), and response in 6 patients (24%). Out of 18 patients treated for longer than 6 months, 83% were in remission or response after 12 months of treatment. The mean duration of remission and response was 10.8 +/- 8.8 months. Steroid withdrawal was possible in 12/16 patients (75%) receiving steroids at methotrexate introduction. Adverse effects were observed in 6 patients (24%) including nausea and vomiting in 3, elevation of liver enzymes in 2 and pancreatitis in 1 patient. CONCLUSIONS: Methotrexate is beneficial in maintaining remission and steroid-sparing treatment in children with Crohn disease following failure of thiopurine therapy.

Does warming up prevent injury in sport? The evidence from randomised controlled trials?

BACKGROUND: The practice of warming up prior to exercise is advocated in injury prevention programs, but this is based on limited clinical evidence. It is hypothesised that warming up will reduce the number of injuries sustained during physical activity. METHODS: A systematic review was undertaken. Relevant studies were identified by searching Medline (1966-April 2005), SPORTDiscus (1966-April 2005) and PubMed (1966-April 2005). This review included randomised controlled trials that investigated the effects of warming up on injury risk. Studies were included only if the subjects were human, and only if they utilised other activities than simply stretching. Studies reported in languages other than English were not included. The quality of included studies was assessed independently by two assessors. RESULTS: Five studies, all of high quality (7-9 (mean=8) out of 11) reported sufficient data (quality score>7) on the effects of warming up on reducing injury risk in humans. Three of the studies found that performing a warm-up prior to performance significantly reduced the injury risk, and the other two studies found that warming up was not effective in significantly reducing the number of injuries. CONCLUSIONS: There is insufficient evidence to endorse or discontinue routine warm-up prior to physical activity to prevent injury among sports participants. However, the weight of evidence is in favour of a decreased risk of injury. Further well-conducted randomised controlled trials are needed to determine the role of warming up prior to exercise in relation to injury prevention.

Health-related quality of life among children and adolescents: associations with obesity.

OBJECTIVE: To assess the impact of obesity on health-related quality of life (HRQOL) of children, and to compare HRQOL scores of obese children in a hospital versus community setting. DESIGN: A cross-sectional study in two clinical samples. SUBJECTS: A total of 182 children and adolescents recruited from the community pediatric clinics and a hospital-based obesity clinic. MEASUREMENTS: Obesity was defined as body mass index (BMI) >95th percentile for age and gender. Subjects were divided into quartiles of BMI Z-scores each containing 45 or 46 children. The first two quartiles correspond to normal BMI, 3rd and 4th quartiles represent moderate and severe obesity, respectively. HRQOL was assessed by the Pediatric Quality of Life Inventory (PedsQL) questionnaire submitted by both children and their parents. RESULTS: Obese children reported significantly lower HRQOL in physical, social and school domains compared with normal weight children (P<0.01). Analyzing results of HRQOL by BMI quartiles showed that the emotional and school domains scores of the moderately obese children were similar to the normal BMI quartiles. Only in the 4th quartile, that of children with severe obesity, were scores significantly lower. In contrast, in both physical and social domains scores decreased progressively with increased BMI Z-scores. In the obese group, parents' scores were lower than the children's in all domains. HRQOL scores of obese children assessed in the hospital clinic were similar to that of obese children assessed in the community. CONCLUSIONS: Moderately obese children had similar emotional and school HRQOL scores as normal weight children, whereas in the physical domain, a significant difference was documented even in moderate obesity. Parents of obese children perceived their child's HRQOL lower than the children themselves. We believe that intervention programs aimed at improving HRQOL should be directed to both parents and children. Understanding the resilience of moderately obese children in school and emotional domains may assist us in the management of childhood obesity.

Golf injuries--common and potentially avoidable.

Injuries sustained during golf rarely receive the recognition given to injuries from sports perceived as more violent or strenuous. However, golfing injuries are believed to occur frequently. The aim of this study was to explore the injury profile of female golfers, including treatment sought and the impact of the injury on performance and participation. Forty-one team captains were given questionnaires to distribute to their players. A total of 522 golfers participating in the Victorian Women's Pennant Competition in Victoria, Australia, from both the Metropolitan and Country competitions, completed the study. Over one-third (35.2%) of the golfers reported having sustained a golfing injury within the previous 12 months, with the lower back being the most commonly injured body region. Strains were the most frequent type of injury (67.9%). Of the 184 injuries reported, 154 sought treatment from a health professional. Physiotherapists were the most common health professional consulted. Performance was affected in 78.9% of cases, with 69.7% of the injured golfers missing games or practice sessions due to injury. Golfing injuries appear common and have a substantial impact upon the injured golfer. As lower back strains are the most common injury, strategies such as performing an appropriate warm-up could be investigated to determine the possible injury prevention benefits for golfers. This study has also highlighted that the majority of treatments are from allied health professionals, suggesting that a complete epidemiological description of golf injuries requires information from broader settings than general practice clinics and hospitals.

Improving golf performance with a warm up conditioning programme.

OBJECTIVES: To determine whether a golf specific warm up programme (both immediately prior to play and after performing it five times a week for 5 weeks) improved performance in 10 male golfers compared with 10 controls matched for age, sex, and handicap. METHODS: Twenty male golfers were matched for age (+/-2 years) and handicap (+/-1 stroke). Club head speed was assessed by two dimensional video analysis in a laboratory setting. In week 1, all golfers performed 10 strokes. In weeks 2 and 7, the controls underwent the same procedure as in week 1. The exercise group performed the golf specific warm up followed by their 10 strokes. Between weeks 2 and 7, the exercise group performed the specially designed warm up five times a week for 5 weeks. RESULTS: The mean club head speeds of the exercise group improved at each testing week. Between weeks 1 and 2, golfers in the exercise group improved their club head speed on average by 3-6 m/s (12.8%), and between weeks 1 and 7, they increased their club head speeds by 7-10 m/s (24.0%). With the exception of one golfer whose club head speed varied by 1.7 m/s, the mean club head speeds of the golfers in the control group hardly varied over the testing period (range: 0.3-0.8 m/s). A significant difference (p = 0.029) was found between the mean club head speeds of the exercise and control groups over the duration of the study, and a significant interaction over time (p<0.001) was also found. CONCLUSIONS: This study has shown that golfers' performances will be significantly improved by undertaking a golf specific warm up programme compared with not performing the warm up.

How well does club head speed correlate with golf handicaps?

The velocity at which a golf club impacts with a golf ball is known as club head speed. Although club head speed has been used to measure performance changes in a number of golf studies, it has not been validated as a golf performance measure. As handicap is the usual measure of performance, the purpose of this study was to investigate the relationship between club head speed and handicap, and to determine whether club head speed at impact is a valid measure of golfing performance. Forty-five male golfers aged 18-80 years, all with registered golfing handicaps (2-27), participated in this study. Each golfer performed 10 golf swings captured by a high-speed camera. Golfers' club head speeds were determined using Video Expert 2, a biomechanical computer program. Golfers with a lower handicap (i.e., a better skill level) had faster club head speeds than higher handicap golfers. Linear regression analysis found club head speed to be highly correlated with handicap (r = 0.950). This relationship was described by the equation: In (club head speed)= 4.065 - 0.0214 x handicap. In conclusion, this study has shown that club head speed is a valid indicator of performance in golfers and may therefore be a useful performance measure in future laboratory-based studies.

Warm-up attitudes and behaviours of amateur golfers.

Although it is widely recommended that golfers warm-up before play/practice to enhance their physical performance and to prevent injuries, few actually undertake this activity. The reasons why golfers do/do not warm-up are not known. The aim of this study was to determine the self-reported behaviours and attitudes of adult golfers towards warming-up. A survey of 1040 randomly selected golfers was conducted over a 3-week period in July 1999. Information about golf participation, usual warm-up habits and reasons for these warm-up behaviours was obtained by a verbally administered self-report survey. Over 70% of the surveyed golfers stated that they never or seldom warm-up, with only 3.8% reporting warming-up on every occasion. The most common reasons why golfers warmed-up included to play better (74.5%), to prevent injury (27.0%), and because everyone else does (13.2%). Common reasons for not warming-up were the perception that they don't need to (38.7%), don't have enough time (36.4%) and can't be bothered (33.7%). These findings suggest that in order to increase the proportion of golfers who warm-up, education programs focussing on the benefits of warming-up, including injury prevention, need to be developed and implemented. Different strategies may need to be adopted to accommodate golfers' differing attitudes and baseline behaviours.

Warm up practices of golfers: are they adequate?

BACKGROUND: Although it is widely recommended that golfers warm up before play or practice to enhance their physical performance and reduce their injury risk, it is not known to what extent they actually undertake such warm up procedures. OBJECTIVE: To collect information about the proportion of golfers who actively warm up and to determine the types of warm up behaviours. METHODS: This study was conducted over three weeks at three different golfing venues: a private golf course, a public golf course, and a golf driving range. Golfers' warm up behaviours, defined as any form of preparative exercise, were recorded by direct observation by two independent observers. RESULTS: The sample consisted of 1040 amateur golfers (852 men and 188 women) aged at least 18 years. Only 54.3% (95% confidence interval 49.8 to 58.8) performed some form of warm up activity. Air swings on the tee were the most commonly observed warm up activity, with 88.7% (95% confidence interval 85.9 to 91.5) of golfers who warmed up performing these. CONCLUSIONS: Only a small proportion of amateur golfers perform appropriate warm up exercises. To improve on this, golfers should be educated about the possible benefits of warming up and be shown how to perform an appropriate warm up routine.

Relevance of CagA positivity to clinical course of Helicobacter pylori infection in children.

A potential virulence determinant of Helicobacter pylori is the cagA gene product. To determine the relevance of the expression of CagA to the clinical picture and outcome of H. pylori infection in children, we examined 104 consecutive children diagnosed with H. pylori infection. Serum samples were collected to test for the presence of immunoglobulin G (IgG) anti-CagA antibodies. Forty-five patients (43%) had antibodies to the CagA protein (group I), and 59 did not (group II). Seropositive patients had a longer prediagnostic history of abdominal pain (P = 0.02), more severe abdominal pain (defined as ulcer pain) (P = 0.05), a higher prevalence of duodenal ulcer (38 versus 7%; P<0.01), more active chronic gastritis (82 versus 32%; P<0.001), and a higher titer of serum IgG anti-H. pylori antibodies (P<0.001). Ninety percent of the patients were monitored for 27+/-18 months. On multivariate analysis, CagA-negative patients had a 3.8-fold-higher chance of achieving a disease-free state than CagA-positive patients (95% confidence interval, 1.5- to 9.5-fold). We conclude that infection with CagA-producing strains of H. pylori is a risk factor for severe clinical disease and ongoing infection.

Upper gastrointestinal bleeding due to gastric ulcers in children with gastrostomy tubes.

The authors describe four children with gastrostomy tubes (G-tubes) presenting with upper gastrointestinal bleeding due to gastric ulcers years after G-tube insertion. They review the literature and discuss the possible mechanisms of gastric ulcer formation in these patients.

The value of anti-Helicobacter pylori IgG antibodies in establishing eradication of infection in children.

The aim of this study was to evaluate the performance of anti-Helicobacter pylori (H. pylori) IgG antibodies in monitoring eradication of infection in children. Forty-seven H. pylori-infected children (aged 12.5 +/- 3.0 years, range 6.5-18 years) were followed for a mean of 30.3 months (range 6.66 months). Patients were divided into those with eradicated infection and those with ongoing infection, as determined by antral biopsy-related tests (histology, urease and culture). Anti-H. pylori antibodies (EIA) were tested at diagnosis and follow-up and changes of antibody titers were compared between the two groups. Twenty-five of 26 non-eradicated patients showed persistently high levels of antibodies throughout the study. One patient had non-detectable antibodies despite an ongoing infection for 12 months. Patients with eradicated infection showed a progressive fall of antibody levels from 52.9 +/- 32.4 U/ml at diagnosis to 17.5 +/- 4.1 U/ml at 6 months (p < 0.007) and 4.4 +/- 0.7 U/ml at > or = 12 months (p < 0.002). In 17 of 21 eradicated patients, serum antibodies normalized during the follow-up period; in 4 of the 21 patients, a decrease of > or = 40% of the initial value was observed during the 8-month follow-up. The validity of serology in the evaluation of H. pylori infection had a sensitivity of 100%, specificity of 96% and positive predictive and negative predictive values of 95% and 100% respectively. Our conclusion is that serial determination of anti-H. pylori antibodies is a reliable method for the follow-up and monitoring of H. pylori eradication in children and adolescents.

Serum pepsinogen I in childhood Helicobacter pylori gastritis: its relation to mucosal peptic activity.

Serum pepsinogen I (PG I) levels are raised in children with Helicobacter pylori gastritis. To ascertain if this is due to increased production or to increased secretion of pepsin by chief cells, we measured mucosal peptic activity in antrum and gastric body mucosal homogenates and correlated it to serum PG I levels in 122 children with and without H. pylori gastritis. In patients infected with H. pylori, mucosal peptic activity was decreased when compared to control and to children with non H. pylori gastritis. Serum PG I levels were increased (P < 0.001) and were inversely related to mucosal peptic activity (P < 0.01). These findings suggest that H. pylori can promote a leakage of pepsinogen into the circulation.

Colchicine enhances intestinal permeability in patients with familial Mediterranean fever.

OBJECTIVE: Colchicine therapy is complicated by frequent gastrointestinal adverse effects. METHODS: We compared intestinal permeability in 21 patients with familial Mediterranean fever on long-standing colchicine therapy (mean 5.8 years) and significant gastrointestinal complaints and 12 untreated patients and 14 healthy volunteers. The double probe (lactulose/mannitol) permeability test was performed using a hyperosmolar test solution (1580 mosmol) and the differential urinary recovery ratios were calculated. RESULTS: Familial Mediterranean fever patients on colchicine therapy had significantly higher lactulose/mannitol urinary excretion ratios (0.073) compared to untreated patients (0.035) and to healthy controls (0.021). Untreated familial Mediterranean fever patients had significantly greater urinary lactulose/mannitol recovery ratios than controls (P < 0.02). No correlation was found between the degree of enhanced permeability and the length of exposure to the drug or the severity of clinical symptoms. CONCLUSIONS: Intestinal permeability was significantly enhanced in patients with familial Mediterranean fever treated with colchicine.

Colchicine-induced lactose malabsorption in patients with familial Mediterranean fever.

Abdominal pain and diarrhea are frequent side effects of chronic colchicine therapy. Drug-induced lactose deficiency has been demonstrated in the experimental animal. Lactose malabsorption was assessed by the lactose breath test in 23 patients with familial Mediterranean fever (FMF) receiving colchicine for 0.25-15 years (mean 3.16). Twenty FMF patients not receiving colchicine and 38 non-FMF lactose malabsorbers served as controls. Patients receiving colchicine had a significantly higher percentage of lactose malabsorption (20/23, 87%) versus nontreated FMF patients (13/20, 65%; P < 0.05). Lactose intolerance was also more prevalent in colchicine-treated patients (17/23, 74%) versus nontreated FMF (5/20, 25%; P < 0.0005) and control lactose malabsorbers (16/38, 42%; P < 0.01). Of the 12 patients investigated before and 3 months after colchicine administration, 7 showed induction or aggravation of lactose malabsorption. The lactose-free diet resulted in partial improvement of symptoms. Colchicine induces significant lactose malabsorption in FMF patients and this is partially responsible for the gastrointestinal side effects of the drug.

Colchicine induces enhanced intestinal permeability in the rat.

Intestinal permeability was determined in rats receiving colchicine 0.5 +/- 0.15 mg day-1 in drinking water (30 mg L-1) for periods up to 23 days. The lactulose/mannitol method was used to determine whole gut permeability before and on days 2, 4, 8, 18 and 23 of colchicine administration. The 8-h urinary lactulose excretion following the test meal increased significantly in rats receiving colchicine, compared with the pretreatment value. Increased lactulose permeability was present after 2 days and remained stable throughout the experimental period. Mannitol urinary excretion was not changed. Colchicine increases intestinal tight junction permeability by an as yet undetermined mechanism.

HLA-B5 in the diagnosis of Behcet's disease.

Behçet's disease, a multisystem disease is, by its nature, difficult to diagnose. The first manifestation of the disease may precede the appearance of other symptoms and signs essential for diagnosis by many years. In patients of Mediterranean origin, the early manifestations of the disease, may be confused with those of familial Mediterranean fever (FMF). Determination of HLA-B5 may, however, contribute to the diagnosis in children with partial manifestations of Beh,cet syndrome.

Choledocholithiasis in infants: diagnostic and therapeutic problems.

During the 3-year period, January 1986 through December 1988, 7 of 24 infants evaluated for cholestatic liver disease were found to have choledocholithiasis with or without associated gallbladder disease. Five were born prematurely with associated predisposing factors, especially systemic infection and total parenteral nutrition. The clinical course varied from spontaneous recovery in two patients to ongoing liver disease requiring surgical or endoscopic intervention in five infants. Asymptomatic patients with normal liver function and persistently dilated extrahepatic biliary trees posed the most difficult therapeutic problems. Endoscopic retrograde cholangiography appeared to be an effective and rewarding therapeutic approach.

The effect of post-natal malnutrition on pepsinogen secretion receptors in weanling rats.

Post-natal malnutrition was induced in rats using the expanded litter model. Pepsinogen secretion of isolated gastric glands in response to several secretagogues was measured. Malnourished 19-day-old pups showed no response to carbachol, CCK-8, gastrin, secretin and ionophore A23187 compared to well-nourished animals, but showed comparable secretion of pepsinogen after stimulation with dibutyryl cAMP (DiBcAMP). Hydrocortisone treatment for 48 h caused increased pepsinogen accumulation and elevated pepsinogen secretory responsiveness to carbachol and secretin of gastric glands isolated from post-natal malnourished pups. Our results indicate that isolated gastric glands obtained from well-nourished rat possess two functionally distinct receptors for gastrin and C-terminal fragment of CCK. Our study supports the concept that in malnourished rats there is a decreased number of binding sites or/and some post-receptor defects. Pepsinogen release mechanisms remain unaffected.

Skin testing with extracts of fungal species derived from the homes of allergy clinic patients in Toronto, Canada.

Airborne fungi in the homes of patients with allergic rhinitis or asthma, from a Toronto Allergy Clinic population, were isolated, quantified and identified to species. Allergen extracts were prepared from sixteen of these isolated species and used for skin-prick testing of twenty-six patients. Fourteen of the total patients reacted to one or more of these extracts at 1:10 (w/v) concentrations. The most common positive skin responses (8/14 to 6/14) were found for Cladosporium cladosporioides, Alternaria tenuis, C. sphaerospermum, and Fusarium sp. The two Cladosporium species were also most commonly isolated in homes, but A. tenuis and Fusarium sp. were found only in 4% and less than 1% of the air samples, respectively. Epicoccum purpurascens and C. herbarum, which were isolated on approximately 10% of the plates, showed fewer skin reactions compared with the above. Positive skin-test response to the other ten study extracts ranged from 5/14 for two species of Aspergillus and Phoma glomerata, to 1/14 for Penicillium viridicatum; of these species, Aspergillus fumigatus was isolated in 3% of the home samples, the others were less than 1%. The findings suggest that fungal antigens from species found in homes are commonly associated with skin sensitization in an allergy clinic population with upper or lower respiratory allergy. No specific relationships were found, however, between the prevalence of fungal species in the home environment and their prevalence as skin-test allergens.