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Biomedical subjects

J Harper

Publications and source records attributed to J Harper.

At least 19 recordsLinked to original sources

Comparison of the efficacy of an existing versus a locally developed metabolic fingerprint database to identify non-point sources of faecal contamination in a coastal lake.

A comparison of the efficacy of an existing large metabolic fingerprint database of enterococci and Escherichia coli with a locally developed database was undertaken to identify the sources of faecal contamination in a coastal lake, in southeast Qld., Australia. The local database comprised of 776 enterococci and 780 E. coli isolates from six host groups. In all, 189 enterococci and 245 E. coli biochemical phenotypes (BPTs) were found, of which 118 and 137 BPTs were unique (UQ) to host groups. The existing database comprised of 295 enterococci UQ-BPTs and 273 E. coli UQ-BPTs from 10 host groups. The representativeness and the stability of the existing database were assessed by comparing with isolates that were external to the database. In all, 197 enterococci BPTs and 179 E. coli BPTs were found in water samples. The existing database was able to identify 62.4% of enterococci BPTs and 64.8% of E. coli BPTs as human and animal sources. The results indicated that a representative database developed from a catchment can be used to predict the sources of faecal contamination in another catchment with similar landuse features within the same geographical area. However, the representativeness and the stability of the database should be evaluated prior to its application in such investigation.

Animals↗

Is the E133K allele of VG5Q associated with Klippel-Trenaunay and other overgrowth syndromes?

BACKGROUND: It has been reported that the activating mutation, E133K, in the angiogenic factor VG5Q (formally named AGGF1) causes Klippel-Trenaunay Syndrome (KTS), a rare vascular disease associated with asymmetric overgrowth. This proposal followed from the observation that five out of 130 KTS patients were constitutionally heterozygous for VG5Q, E133K. OBJECTIVE: To explore the possibility that VG5Q, and specifically E133K, is implicated in other mosaic overgrowth syndromes. RESULTS: 24 patients were analysed for this sequence change. One patient was constitutionally heterozygous for E133K. Analysis of both parents revealed that the patient's mother, who was healthy, also carried E133K. An analysis of 275 healthy controls showed that 3.3% (9/275) of the population were carriers of E133K. CONCLUSIONS: The findings bring into question the assertion that VG5Q, E133K is a mutation and that it causes KTS.

Amino Acid Substitution↗

Bone mineralization in children with epidermolysis bullosa.

BACKGROUND: Various factors may have deleterious effects on bone health in patients with epidermolysis bullosa (EB). OBJECTIVES: In a retrospective notes review, to assess bone mineralization in children with EB and to identify the relative contributions of nutrition, activity and disease severity to low bone mass. METHODS: Thirty-nine children with EB [32 recessive dystrophic EB (RDEB), four Dowling-Meara EB simplex (DMEBS) and three junctional EB (JEB)] had lumbar spine bone mass measured using dual X-ray absorptiometry (GE Lunar Prodigy; GE Healthcare, Chalfont St Giles, U.K.). Seventy-six healthy children were also studied. Weight and height were recorded and mobility was rated. RESULTS: Children with RDEB and JEB, but not those with DMEBS, had lower bone mineral density SD scores than controls; differences remained after adjusting for the smaller body size of the patients. Bone mass was best predicted by mobility rating. CONCLUSIONS: Children with RDEB and JEB have low bone mass after adjusting for their smaller size, which may put them at risk for fragility fractures. Low bone mass was best predicted by the level of mobility, raising the hypothesis that improving activity or bone loading may be a potential preventive intervention in these children. However, as low bone mass may be multifactorial in these children, more detailed investigation of potential aetiological factors is required before interventions are planned.

Absorptiometry, Photon↗

Peripherally inserted central catheters and upper extremity deep vein thrombosis.

The purpose of the study was to determine the incidence and risk factors for venous thrombosis in patients with a peripherally inserted central catheter (PICC). A retrospective study of all upper extremity venous duplex scans was carried out in the Vascular Medicine department from year 2000 to 2002 inclusive. A chart review of positive scans was undertaken to identify possible thrombotic risk factors. Of 317 upper extremity venous duplex scans carried out, 115, or 32%, were positive for upper extremity deep vein thrombosis. Three main risk factors were identified - presence of a central line, malignancy and administration of chemotherapy. PICC were the most common central line present. Symptomatic thrombosis occurred in 7% of PICC inserted for chemotherapy compared with 1% of PICC inserted for other reasons. Ten per cent of the patients receiving chemotherapy through a PICC developed a thrombosis. The post-thrombotic syndrome was infrequent following upper extremity deep vein thrombosis. Patients receiving chemotherapy through a PICC are at increased risk of thrombosis. There may be a role for prophylactic low-dose anticoagulation in these high-risk patients.

Adolescent↗

Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel's opinion and review of the literature.

BACKGROUND: The use of dampened bandages to reduce inflamed eczema (synonyme dermatitis) is an old remedy. In order to evaluate the current indications for so-called wet-wrap treatment (WWT) for atopic dermatitis (AD), and to compare the different currently recognized methods, a group of experts critically reviewed their own expertise on WWT in respect to the existing literature on the subject. RESULTS: WWT is well tolerated in eczema due to the cooling effect on the skin and the rapid improvement in skin inflammation. It has been shown to be an extremely effective treatment for acute erythrodermic dermatitis, therapy-resistant AD and intolerable pruritus. Advantages of WWT include rapid response to therapy, reduction in itch and sleep disturbance, and potential for reduction in usage of topical corticosteroids (TCS). However, disadvantages include high cost, the necessity for special training in usage, potential for increased TCS absorption, increased cutaneous infections and folliculitis, and poor tolerability. Precautions to reduce the risks of long-term treatment should include education, monitoring of weight and height and, if necessary, serum cortisol levels. In adolescents the risk of striae from TCS absorption around puberty is high, and WWT with TCS in this age group should be used as a short-term therapy only and with extreme caution. To reduce risks, dilutions of steroids may be used ranging from 5 to 10%. In the maintenance phase this treatment can be rotated with the use of emollients only. Low potency TCS should be used on the face (with a mask). CONCLUSION: WWT using diluted steroids is a relatively safe addition to the therapeutic treatment options for children and adults with severe and/or refractory AD. Explanation and education is extremely important in the treatment of AD and WWT should only be employed by practitioners trained in its use. Specialized nursing care is essential, especially when using WWT for prolonged periods.

Bandages↗

Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study.

OBJECTIVE: Juvenile localized scleroderma (JLS) includes a number of conditions often grouped together. With the long-term goal of developing uniform classification criteria, we studied the epidemiological, clinical and immunological features of children with JLS followed by paediatric rheumatology and dermatology centres. METHODS: A large, multicentre, multinational study was conducted by collecting information on the demographics, family history, triggering environmental factors, clinical and laboratory features, and treatment of patients with JLS. RESULTS: Seven hundred and fifty patients with JLS from 70 centres were enrolled into the study. The disease duration at diagnosis was 18 months. Linear scleroderma (LS) was the most frequent subtype (65%), followed by plaque morphea (PM) (26%), generalized morphea (GM) (7%) and deep morphea (DM) (2%). As many as 15% of patients had a mixed subtype. Ninety-one patients (12%) had a positive family history for rheumatic or autoimmune diseases; 100 (13.3%) reported environmental events as possible trigger. ANA was positive in 42.3% of the patients, with a higher prevalence in the LS-DM subtype than in the PM-GM subtype. Scl70 was detected in the sera of 3% of the patients, anticentromere antibody in 2%, anti-double-stranded DNA in 4%, anti-cardiolipin antibody in 13% and rheumatoid factor in 16%. Methotrexate was the drug most frequently used, especially during the last 5 yr. CONCLUSION: This study represents the largest collection of patients with JLS ever reported. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome.

Adolescent↗

Insulin-like growth factor ligands, receptors, and binding proteins in cancer.

This review aims to summarize experimental evidence supporting the role of the insulin-like growth factor (IGF) signalling system in the progression, maintenance, and treatment of cancer. These data implicate the IGF system as an important modifier of cancer cell proliferation, survival, growth, and treatment sensitivity. The role of the IGF system in cancer should be examined in the context of the extra-cellular and intra-cellular signalling networks, in particular: phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt/PKB), mammalian target of rapamycin (mTOR), and forkhead transcription factors (FOXO). This review highlights evidence derived from molecular structure and functional genetics with respect to how the extra-cellular components of the IGF system function normally, and their subsequent modifications in cancer. The therapeutic relevance of the research evidence described is also addressed, as the challenge is to apply this knowledge to human health.

Amino Acid Sequence↗

Patterns of food allergen-specific cytokine production by T lymphocytes of children with multiple allergies.

BACKGROUND: The contribution of different T cell subsets to the overall measured cytokine response to food allergens is largely unexplored. METHOD: The patterns of cytokine production of peripheral blood-derived T cells after allergen stimulation were studied in 22 children with multiple food allergies and in 20 non-allergic children as controls, using flow cytometry. RESULTS: Proportions of T cells of food-sensitized children spontaneously secreting IFN-gamma and IL-10 (without antigen stimulation) were lower than non-atopic children and adult controls (P<or=0.001). The proportions of IL-4-producing cells in vitro were significantly increased (P<or=0.04) and IFN-gamma-producing cells were significantly reduced (P<or=0.05) in sensitized children after incubation with and without dendritic cell presentation of peanut extract, beta-lactoglobulin and ovalbumin. The reverse pattern was found in non-sensitized children and adult controls. IL-4 secretion in allergic children to sensitizing allergens was mainly restricted to the CD4(+) CD45 RO(+) population while in non-atopic controls both CD4(+) and CD8(+) CD45 RO(+) cells produced mostly IFN-gamma. Food-specific IgE values did not correspond with cytokine responses but IL-4 production and IFN-gamma reduction relative to normal children were closely associated with total IgE levels. CONCLUSION: Food-allergic children's IL-4 cytokine response to their relevant allergens is predominantly from a memory population of CD4(+) CD45 RO(+) cells, whereas IL-4 and IFN-gamma secretion of non-allergic controls was predominantly from mixed CD4(+) and CD8(+) CD45 RO(+) populations.

Allergens↗

ESHRE PGD Consortium data collection IV: May-December 2001.

The ESHRE PGD Consortium was formed in 1997 to survey the practice of preimplantation genetic diagnosis (PGD). Since then, three reports have been published giving an overview on PGD from an ever-increasing number of centres and reporting on an increasing number of PGD cycles and pregnancies and babies born after PGD. After these initial influential publications, important shortcomings were identified primarily on the method of data collection, i.e. with Excel spreadsheets, and in the timing of the collection (cycles were collected in a different time frame from pregnancies and babies, making the follow-up of cycles very difficult). This is why the Steering Committee has made a major investment in developing and implementing a new database in FileMaker Pro 6. It was also decided that cycles would be collected from one calendar year, as well as the pregnancies and babies ensuing from that particular calendar year. This gave us the opportunity to take a closer look at the data collected earlier, and to attempt to improve their quality. This is a report on the corrected data from the first three data collections (I-III) as well as the result of the last data collection (IV) that was completely carried out using the new database.

Data Collection↗

A blinded laxative taper for patients with eating disorders.

OBJECTIVE: To evaluate a blinded laxative taper, supervised entirely by pharmacists, in eating disorder patients with laxative dependency. METHODS: All subjects received a blinded laxative taper according to a set protocol, in addition to the usual treatment for their eating disorder. No specific treatment was given for laxative dependency other than the pharmacist's supervisions of the blinded taper. RESULTS: Ten patients were enrolled, of whom seven completed the study. Five of the seven patients (71%) decreased their laxative intake by at least 50%. Of these seven patients, three withdraw completely from laxative use. DISCUSSION: A standardized blinded laxative taper shows promise as a treatment option for laxative dependency in patients with eating disorders. The laxative taper may be less costly and more available than inpatient or psychologically based treatment because it can be given on an outpatient basis under the supervision of a pharmacist.

Adult↗

Cutaneous haemangioma: prevalence and sonographic characteristics of associated hepatic haemangioma.

AIMS: To determine the prevalence of hepatic haemangiomas (HH) occurring with multiple or large cutaneous haemangiomas (CH), and compare the ultrasound (US) characteristics of HH with morphology of concurrent CH. MATERIALS AND METHODS: Retrospective and prospective sonographic and clinical analysis was undertaken on 69 patients referred for US to exclude silent HH. This comprised 62 patients referred over 6 years with six or more CH or one large CH (#10878;5 cm) and seven patients referred over 1 year with three to five small CH. RESULTS: HH occurred in 45% miliary CH and 40% mixed small and large CH, but also in 12-14% of patients with one large or three or more small CH. None had HH progression. There was association between HH sonographic characteristics and CH number and morphology. CONCLUSION: Clinically silent HH occurred in nearly one in four of infants presenting overall with six or more small CH or large CH. Previous studies have documented HH mortality between 18 and 80%, although this was not shown in our study. Therefore, if clinical suspicion exists, US is indicated to enable early steroid treatment if significant HH are present.

Child↗

0.03% Tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double-blind controlled trial.

BACKGROUND: Topical corticosteroids are the usual treatment for atopic dermatitis (AD) in children but can have side-effects. OBJECTIVES: This study compared the efficacy and safety of 0.03% tacrolimus ointment applied once or twice daily over a 3-week period with the twice daily application of 1% hydrocortisone acetate (HA) ointment in children with moderate to severe AD. PATIENTS AND METHODS: Patients applied ointment daily to all affected body surface areas. The primary study endpoint was the percentage change in the modified Eczema Area and Severity Index (mEASI) between baseline and treatment end. RESULTS: Six hundred and twenty-four patients, aged 2-15 years, applied 0.03% tacrolimus ointment once daily (n = 207), twice daily (n = 210) or 1% HA twice daily (n = 207). By the end of treatment, application of 0.03% tacrolimus ointment both once or twice daily resulted in significantly greater median percentage decreases in mEASI (66.7% and 76.7%, respectively) compared with 1% HA (47.6%; P < 0.001). Furthermore, the median percentage decrease in mEASI was significantly greater for patients applying 0.03% tacrolimus twice daily compared with once daily (P = 0.007). Patients with severe AD benefited especially from twice daily application of 0.03% tacrolimus ointment compared with once daily application (P = 0.001). Transient mild to moderate skin burning occurred significantly more often in the 0.03% tacrolimus groups (P = 0.028) but resolved in most cases within 3-4 days. Laboratory parameters showed no clinically relevant changes. CONCLUSIONS: 0.03% tacrolimus ointment applied once or twice daily is significantly more efficacious than 1% HA in treating moderate-severe AD in children. Twice daily application of 0.03% tacrolimus ointment results in the greatest improvement in mEASI, and is especially effective in patients with severe baseline disease.

Administration, Topical↗

Minimal internal fixation and calcium-phosphate cement in the treatment of fractures of the tibial plateau. A pilot study.

We used calcium-phosphate cement combined with minimal internal fixation to treat 49 fractures of the lateral tibial plateau. There were 25 split depression fractures, 22 pure depression fractures and two bicondylar fractures. Anatomical reduction was obtained in 38 fractures, satisfactory reduction in nine and imperfect reduction in two. Of 44 patients reviewed at one year, 33 were rated as having an excellent reduction. Functional outcome as measured by the Rasmussen score was good or excellent at six months in 92% (44/48) of patients and in 95% (42/44) at one year. Eight (16%) showed some loss of reduction of the plateau. In seven of these the loss of reduction was slight (<3 mm) and no action was taken. One patient with a deep infection had gross loss of reduction and a poor functional outcome. Calcium-phosphate cement is a useful alternative to bone grafting for the treatment of fractures of the tibial plateau.

Adult↗

Nutritional supplementation in older adults: pleasantness, preference and selection of sip-feeds.

OBJECTIVES: Malnourishment is common in older adults, and nutritional supplementation is used to improve body weight and well-being. Clinical reports suggest, however, that patients routinely reject sip-feeds. The present study examined the following questions: whether sip-feeds are less preferred and less likely to be selected than other energy-dense foods in healthy elders; and whether eating alone further reduces intake relative to eating in a social setting. METHODS: Twenty-one healthy older adults (aged 60-79 years) attended the laboratory on three occasions. Subjects rated six different flavours of sip-feed and then rated the pleasantness of the taste of the favoured flavour against five other energy-dense familiar foods/drinks. Intake of these foods was measured when subjects ate alone or in a group of familiar others. RESULTS: Favourite flavour of sip-feed compared well with other more familiar foods and was selected as part of a snack. Snack intake increased by 60% when consumed in a group setting compared with eating alone. CONCLUSIONS: The study suggests that sip-feeds are rated as pleasant and selected by free-living elders. Rejection of sip-feeds in hospitalized elders may relate more to loss of appetite than to the taste preference for sip-feeds, and that eating alone rather than in groups of familiar others is likely to compound eating problems.

Aged↗

Raised limb bands developing in infancy.

Congenital cutaneous constriction bands are rare and often occur with other abnormalities, including the presence of rudimentary digits. This diverse syndrome lacks a precise definition and a satisfactory explanation. We describe two unusual cases with features previously undescribed, in which predominantly raised, annular limb bands became apparent postnatally. One infant was also born with foreshortened digits and a constricting limb band, suggesting a shared aetiology with other congenital cases. The development of raised bands during infancy would be difficult to reconcile with the widely held 'amniotic band hypothesis', and would be more in keeping with a multifocal developmental abnormality in limb growth.

Abnormalities, Multiple↗

Serum ascorbic acid concentrations in previously unsupplemented greyhounds after administration of a single dose of ascorbic acid intravenously or per os.

Plasma vitamin C concentrations (mean + SD) were measured after a large (1 g) dose of vitamin C was administered orally or intravenously to each of four trained greyhounds in a randomized cross-over design. Concentrations increased (p<0.05) for 2 h but returned to baseline by 6 h after supplementation. Peak concentrations were greater (p<0.01) after intravenous than oral administration (6.1+/-1.2 vs. 0.54+/-0.23 mg/dl). This suggests that vitamin C must be administered many times daily to maintain plasma concentrations above normal.

Administration, Oral↗

Juvenile-onset localized scleroderma activity detection by infrared thermography.

OBJECTIVE: The aim of this study was to define the clinical utility of infrared thermography in disease activity detection in localized scleroderma (LS). METHODS: We retrospectively reviewed 130 thermal images of 40 children with LS and calculated the sensitivity and specificity of thermography, comparing clinical descriptions of the lesions and contemporary thermographs. The reproducibility of thermography was calculated by using the weighted kappa coefficient to determine the level of agreement between two clinicians who reviewed the thermographs independently. RESULTS: The sensitivity of thermography was 92% and specificity was 68%. Full concordance between the two clinicians was observed in 91% of lesions, with a kappa score of 0.82, implying very high reproducibility of this technique. CONCLUSION: Our results demonstrate that thermography is a promising diagnostic tool when associated with clinical examination in discriminating disease activity, as long as it is applied to lesions without severe atrophy of the skin and subcutaneous fat. Further evaluation is needed to determine whether thermography can predict the future progression of lesions.

Age of Onset↗

Functional interaction of calcium-/calmodulin-dependent protein kinase II and cytosolic phospholipase A(2).

Calcium-/calmodulin-dependent protein kinase II (CaM kinase II), a decoder of Ca(2+) signals, and cytosolic phospholipase A(2) (cPLA(2)), an enzyme involved in arachidonate release, are involved in many physiological and pathophysiological processes. Activation of CaM kinase II in norepinephrine-stimulated vascular smooth muscle cells leads to activation of cPLA(2) and arachidonic acid release. Surface plasmon resonance, mass spectrometry, and kinetic studies show that CaM kinase II binds to cPLA(2) resulting in cPLA(2) phosphorylation on Ser-515 and an increase in its enzymatic activity. Phosphopeptide mapping studies with cPLA(2) from norepinephrine-stimulated smooth muscle cells indicates that phosphorylation of cPLA(2) on Ser-515, but not on Ser-505 or Ser-727, occurs in vivo. This novel signaling pathway for arachidonate release is shown to be cPLA(2)-dependent by use of a recently described and highly selective inhibitor of this enzyme.

Animals↗