Motor skill competence and moderate- and vigorous-intensity physical activity: a linear and non-linear cross-sectional analysis of eight pooled trials.

BACKGROUND: Few studies have examined the relationship between motor skill competence and device-measured physical activity in large samples and none have used non-linear modelling. This study assessed the linear and non-linear associations between motor skill competence and physical activity in children using pooled data from eight studies. METHODS: Cross-sectional ActiGraph accelerometer and motor skills competence data from 988 children (50.8% boys) aged 3-11 years were included. Total, object control and locomotor skill competence were assessed using the Test of Gross Motor Skill Development. Linear mixed models were fitted to examine linear associations between motor skill competence and physical activity. Then, restricted cubic splines models were used to assess potential non-linear relationships. Interactions by sex and age were assessed. RESULTS: There was evidence of positive linear associations between total skill, and object control and locomotor skills, with moderate- and vigorous-intensity physical activity; however, the associations with total skill competence and object control better fitted a non-linear model. Non-linear models indicated associations were positive but relatively weak in the low to mid ranges of TGMD/object control scores but at high ranges (~ > 70 out of 100/ and ~ 35 out of 50) the association strength increased for both moderate- and vigorous-intensity physical activity. There were sex interactions for locomotor skills only, specifically for vigorous activity with boys having a stronger positive association than girls. CONCLUSIONS: There appears to be a threshold for object control skill proficiency that children need to reach to enhance their physical activity levels which provides support for a motor skill "proficiency barrier". This provides a tangible benchmark for children to achieve in motor competence programs.

European principles of haemophilia care.

As the management of haemophilia is complex, it is essential that those with the disorder should have ready access to a range of services provided by a multidisciplinary team of specialists. This document sets out the principles of comprehensive haemophilia care in Europe. Within each country there should be a national organization which oversees the provision of specialist Comprehensive Care Centres that provide the entire spectrum of clinical and laboratory services. Depending upon the size and geographical distribution of the population, a network of smaller haemophilia centres may also be necessary. There should be arrangements for the supply of safe clotting factor concentrates which can also be used in home treatment and prophylaxis programmes. A national register of patients is recommended along with collection of treatment statistics. As comprehensive haemophilia care is multidisciplinary by nature, the need for education and research programmes for all staff members is emphasized: Members of the Interdisciplinary Working Group not represented in the list of authors are mentioned in Section 4 of this document.

Plasmacytoid dendritic cells: in vivo regulators of alloimmune reactivity?

Dendritic cells (DC) exhibit remarkable plasticity in terms of their ability to induce and regulate innate and adaptive immune responses. Human and mouse interferon alpha-producing plasmacytoid (p) DC have been found to regulate allogeneic T cell responses in vitro. Evidence is emerging that pDC may also regulate immune reactivity in vivo, including the responses that underlie graft-versus-host disease and organ transplant rejection. These cells may also offer potential for therapy of adverse immune responses and the promotion of tolerance induction.

A 7-year analysis of anti-Gag (p17 and p24) antibodies in HIV-1-seropositive patients with haemophilia: immunoglobulin G titre and avidity are early predictors of clinical course.

OBJECTIVE: To study the humoral immune response to HIV-1 p17 and p24 Gag proteins longitudinally and assess any prognostic value. DESIGN AND METHODS: Fifteen HIV-1 infected patients with haemophilia were asymptomatic at entry to the study in 1986. Each patient was monitored at 6- to 12-month intervals for up to 7 years for p17 and p24 immunoglobulin (Ig)G titres, p17 IgG avidity, total IgG, p24 antigenaemia and CD4 cell counts. Results were correlated with the clinical course. RESULTS: Between 1986 and 1993, six of the patients developed CD4 cell counts below 200 x 10(6)/l (AIDS patients) while nine retained counts above this level (asymptomatic patients). All AIDS patients were characterized by declining IgG titres to p17 and p24 from 1986-1987 onwards. A reduction in specific p17 and p24 IgG preceded, by at least 3-4 years, the onset of CD4 cell depletion (< 200 x 10(6)/l). These six patients also had significantly lower p17 IgG avidity than the asymptomatic patients throughout the study. CONCLUSION: Titres of p17 and p24 IgG appeared to alter in the same manner. A progressive reduction in IgG titres and a low p17 IgG avidity were earlier predictors of disease progression than CD4 cell counts or p24 antigenaemia.

Venous thrombosis following the use of intermediate purity FVIII concentrate to treat patients with von Willebrand's disease.

We describe four patients with von Willebrand's disease (VWD) who experienced venous thrombosis after treatment with an intermediate purity factor VIII (FVIII) concentrate (Haemate P3) was used to cover invasive or surgical procedures. Most patients had additional risk factors for venous thromboembolism (VTE) and it is difficult to be certain of the contribution of the concentrate to the VTE. In view of the recognised association between high factor VIII activity (FVIII:C) levels and VTE there is a physiological basis for this complication and it is important to consider this when administering FVIII containing concentrates to VWD patients.

HLA class II profile: a weak determinant of factor VIII inhibitor development in severe haemophilia A. UKHCDO Inhibitor Working Party.

The risk of developing factor VIII inhibitor antibodies in haemophilia A may relate both to factor VIII genotype and genes within the HLA complex known to influence immune response. We investigated a cohort of 176 patients with severe haemophilia A and with either high-level inhibitors (> 10BU/ml) or with no history of an inhibitor, stratified according to the presence or absence of the factor VIII gene intron 22 inversion. HLA DRB1, DQA1 and DQB1 polymorphisms were determined by PCR. HLA frequencies form 137 United Kingdom controls were used for comparison. HLA phenotype frequency differences, expressed as odds ratios with 95% confidence intervals were as follows: HLA-DRB*1501, DQB1*0602 and DQA1*0102 were all increased in frequency in patients with inhibitors, only DQA1*0102 reaching statistical significance (OR 2.7, 1.2-5.9). These alleles form part of an established HLA haplotype. The frequencies of HLA-DRB1*1501, DQB1*0602 and DQA1*0102 were particularly raised in patients with inhibitors and a factor VIII gene intron 22 inversion, although again only DQA1*0102 achieved significance (OR 3.1, 1.0-10.1). The frequency of DRB1*01, DQB1*0501, DQA1*0101 were also increased in inhibitor patients lacking the intron 22 inversion although this failed to achieve statistical significance. This data suggests that HLA class II profile constitutes a weak risk factor for developing inhibitor antibodies to factor VIII. This may be more pronounced in patients with an intron 22 inversion.

Factor VIII inhibitors in mild and moderate-severity haemophilia A. UK Haemophilia Centre Directors Organisation.

Twenty six patients with mild or moderate haemophilia A and inhibitors are described. The inhibitor was detected at a median age of 33 years, after a median of 5.5 bleeding episodes. This usually following intensive replacement therapy. The median presenting inhibitor titre was antihuman 11.6 BU/ml, antiporcine 1.45 BU/ml. Plasma basal factor VIII level declined from a median of 0.08 IU/ml to 0.01 IU/ml following the inhibitor development. This caused spontaneous bleeding in 22 and a bleeding pattern similar to acquired haemophilia in 17. Bleeding was often severe and caused two deaths. The inhibitor disappeared spontaneously, or following immune tolerance induction, in 16 cases after a median of 9 months (range 0.5-46), with a return to the original baseline VIIIC level and bleeding pattern accompanied inhibitor loss. The inhibitor persisted in the remainder of the cases over a median period of 99 months (range 17-433 months) of follow-up. Inhibitors are an uncommon complication of mild haemophilia which frequently persist and may be associated with severe, life-threatening, haemorrhage. Forty-one percent of treated haemophilic family members had a history of factor VIII inhibitors, suggesting a familial predisposition to develop inhibitors in these kindreds. Sixteen patients from 11 families were genotyped. Seven different missense mutations affecting the light chain were detected and two in the A2 domain. Five patients from three families had a mutation causing a substitution of Trp2229 by Cys in the C2 domain which appears to predispose to inhibitor formation since 7 of the 18 affected individuals have a history of inhibitor development.

Decline in CTL and antibody responses to HIV-1 p17 and p24 antigens in HIV-1-infected hemophiliacs irrespective of disease progression. A 5-year follow-up study.

CTL and antibody responses to HIV-1 p17 and p24 antigens were monitored from 1986-1991, in 4 hemophiliacs. The patients had been infected with HIV-1 between 1980 and 1984. Two patients have remained asymptomatic while two progressed to AIDS in 1990. CTL were boosted by culturing with peptides from p17 aa 86-115, or p24 aa 265-279; and aa 270-373 or PHA. Lysis was measured on autologous or allogeneic targets pulsed with peptides or infected with recombinant vaccinia virus carrying HIV-1 gag or influenza A matrix genes. Antibodies to p17 and p24 were tested by ELISA using peptides and by Western blotting. High levels of CTL activity to p17 and p24 antigens could be generated only with lymphocytes from the two asymptomatic patients between 1986 and 1989, but these responses were absent in 1990 and 1991. Antibodies to p17 peptides disappeared in parallel with CTL activity. Antibodies to some p24 peptides also declined but most patients retained activity to others. In all patients a > or = 3-fold increase in CD8+ cell numbers occurred over time and accompanied the decline of CTL and antibody responses. The loss of CTL and p17 antibodies occurred irrespective of whether patients remained asymptomatic or progressed to AIDS in the intervening two years.

Severe coagulation defect due to a dietary deficiency of vitamin K.

A patient with multiple injuries developed a severe coagulation defect due to a deficiency of vitamin K. None of the usual predisposing factors was present and the patient's diet was very poor. Dietary deficiency of vitamin K and the importance of antibiotic therapy in its production are discussed.

Recommendations for the treatment of factor VIII inhibitors: from the UK Haemophilia Centre Directors' Organisation Inhibitor Working Party.

A strategy is described for the initial detection, management and elimination of factor VIII inhibitors arising in patients with congenital and acquired haemophilia A. It is suggested that children with severe haemophilia A should be screened every 3 months up to the age of 10 years for inhibitors using the Bethesda method. Factor VIII inhibitors arising in these patients should be abolished using immune-tolerance induction wherever possible. Such regimes should be started as early as possible, preferably when the inhibitor titre is < 10 Bethesda Units (BU)/ml, and should not be interrupted. High-intensity regimes are recommended for patients whose inhibitors exceed 10 BU. Autoantibodies to factor VIII giving rise to acquired haemophilia should be abolished using high-dose immunoglobulin or conventional immunosuppression. The choice of haemostatic agent for the treatment of severe bleeding should be based upon the clinical circumstances and the current inhibitor value, measured using both human and porcine factor VIII in the Bethesda assay. The past anamnestic response should also be considered when choosing treatment for minor bleeding episodes.

The toxicologic investigation of a feed grain contaminated with seeds of the plant species Cassia.

Feed grain suspected of causing death in a group of pigs was evaluated for toxic potential in chickens. The contaminated grain sorghum mixture was examined visually and contained 3.7% Cassia occidentalis and 1.6% Cassia obtusifolia seeds by weight. Thirty-two chicks were fed a sample of this suspect grain sorghum mixture. Chickens receiving the contaminated grain lost weight rapidly, exhibited clinical signs typical of intoxication with Cassia spp., and by day 16 were severely debilitated. Necropsy and histologic and electron microscopic examinations demonstrated a skeletal and cardiac degenerative myopathy consistent with intoxication by Cassia occidentalis. These toxicologic investigations verified the toxic potential of the contaminated sorghum mixture for chickens, and these comparative observations support prior diagnostic efforts implicating Cassia spp. as a cause of illness in swine.

Fumonisin toxicosis in swine: clinical and pathologic findings.

From a series of experimental studies with pigs (12-16 kg), either pulmonary edema or liver failure emerged as a distinct pathogenetic expression of fumonisin B1 (FB1) toxicosis. The primary determinant as to which pathogenetic consequence developed was the quantity (dose) of the mycotoxin fed or intubated per kilogram of body weight per day. Pigs intubated with a minimum of 16 mg FB1/kg/day developed severe interlobular edema with or without hydrothorax and variably severe pulmonary edema. Pigs intubated with < 16 mg FB1/kg/day or pigs fed diets containing 200 mg FB1/kg of feed developed marked icterus and hepatocellular necrosis. The spectrum of degrees of severity of pulmonary edema observed in the experimental pigs allowed rational speculation regarding evolution of the pathologic changes.

Pulmonary edema and hydrothorax in swine produced by fumonisin B1, a toxic metabolite of Fusarium moniliforme.

Pulmonary edema and hydrothorax were observed in mature swine that died approximately 5 days after consuming corn screenings. These postmortem observations were reproduced in younger swine (16-24 kg) that died within 1 week when fed the corn screenings under experimental conditions. Additionally, pulmonary edema and hydrothorax occurred in a pig (7.1 kg) that died after receiving 4 daily intravenous injections of fumonisin B1. A fungus was isolated from the corn screenings that is identical to Fusarium moniliforme MRC-826 in colony morphology and under microscopic examination.

Toxoplasma gondii antibodies in common barn-owls (Tyto alba) and pigeons (Columba livia) in New Jersey.

In southwestern New Jersey during 1986 and 1987, common barn-owls and pigeons were captured on farmsteads and tested for Toxoplasma gondii antibodies by a modified direct agglutination test. In 1986, 3/28 (10.7%) adult and 0/124 nestling owls tested positive at titers of greater than or equal to 1:40. Additionally, 2/34 (5.9%) pigeons tested had T. gondii antibodies at titer of 1:320. In 1987, 9/38 (27.3%) adult and 18/80 (22.5%) nestling owls tested positive at titers of greater than or equal to 1:25; this includes 3/38 (7.9%) adult and 1/80 (1.3%) nestling owls that tested positive at a titer of 1:50.

Salmonella spp. in nestling common barn-owls (Tyto alba) from southwestern New Jersey.

The prevalence of Salmonella spp. in nestling common barn-owls was investigated in southwestern New Jersey during the summer of 1985. Of 94 owls sampled by swabbing the cloaca, eight (8.5%) were found to harbor Salmonella spp. Three serotypes--S. thompson, S. tuindorp, and S. typhimurium--were identified. Five (20%) of the 25 nest sites examined (all of them in or near farm buildings or dwellings) contained Salmonella-positive owls.

Acute, fatal illness in cattle exposed to boron fertilizer.

Twenty-six cows died after accidental exposure to boron fertilizer. Cows developed diarrhea, weakness, ataxia, signs of depression, and died, usually within a few hours. Seizure-like behavior was noticed in 2 cows, and 2 were suspected of aborting. High boron concentrations in tissues from affected cows confirmed ingestion of an appreciable amount of boron fertilizer. In an attempt to confirm the diagnosis of boron poisoning, boron fertilizer was administered to goats. A kid goat given 3.6 g of fertilizer/kg of body weight developed clinical signs similar to those seen in the cattle. Boron compounds such as sodium borate and boric acid have been considered generally nontoxic, and reports of livestock toxicosis are uncommon. This case report suggests that these compounds may be palatable under certain circumstances leading to ingestion of toxic quantities.

Aflatoxicosis in cattle pastured in a field of sweet corn.

Aflatoxicosis was diagnosed in a small herd of cattle having access to moldy, unharvested sweet corn. Necropsy of 1 cow that died revealed anasarca and a pale tan liver. In this cow, microscopic examination revealed edema of all soft tissues and liver lesions consistent with aflatoxicosis. Samples of corn taken from the field contained 2,365 ng of aflatoxin/g of corn. Weather conditions were conducive to the formation of aflatoxins by Aspergillus flavus and A parasiticus.

Aflatoxicosis in feeder cattle.

Aflatoxicosis was diagnosed as the cause of deaths in a group of crossbred feeder steers. Corn used in the ration being fed the steers was found to be contaminated with 1,500 ng of aflatoxin/g. Residues of the mycotoxin were detected in kidney tissue, and microscopic examination of liver sections revealed lesions typical of aflatoxicosis.

Cassia occidentalis toxicosis in growing pigs.

Approximately 70 feeder pigs developed ataxia and other signs of neuromuscular dysfunction. The ration fed the pigs was found to be contaminated with Cassia occidentalis seeds. Experimentally, other feeder pigs were fed this ration, and they developed ataxia and other signs of neuromuscular dysfunction within 6 to 8 weeks. In further experiments, feeder pigs fed diets containing 1%, 2%, or 4% ground cassia seeds also became intoxicated. Microscopically, diaphragmatic myopathy and pancreatic tissue necrosis were the principal pathologic findings.