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Biomedical subjects

H Allen

Publications and source records attributed to H Allen.

At least 19 recordsLinked to original sources
PubMed2005

The WHO dose pole for the administration of praziquantel is also accurate in non-African populations.

In 2001, WHO developed a pole for the administration of praziquantel without the use of weighing scales, with encouraging results in African populations. In the present study, the pole was tested on height/weight data from 9354 individuals from 11 non-African countries. In more than 98% of the individuals (95% CI 97.8-98.4) the pole estimated an acceptable dosage (30-60 mg/kg), a performance statistically similar to that observed in African populations. Reproducing the present pole in the form of a strip of paper and including it in each container of praziquantel would greatly facilitate the administration of the drug in large-scale interventions.

Adolescent↗
PubMed2002

Drug-induced extrapyramidal reactions.

A child with psychotic symptoms and attention-deficit hyperactivity disorder who developed extrapyramidal symptoms while on a combination of risperidone, methylphenidate, sertraline, tropisetron and ketorolac is described herein. The extrapyramidal symptoms resolved with the administration of benztropine, an anticholinergic drug. Successful treatment of his psychosis was achieved by decreasing the dose of risperidone, followed by slow upward titration.

Antipsychotic Agents↗
PubMed2002

Survey of the use of complementary medicines and therapies in children with asthma.

OBJECTIVE: To survey the frequency of use of complementary medicines (CM) and complementary therapies (CT) in asthmatic children. METHODOLOGY: A 3-month survey of asthmatic inpatients and outpatients of a teaching hospital respiratory paediatrician was undertaken. Parents answered a structured questionnaire about their past and present usage and opinions of CM and CT. Parents and the physician independently assessed overall asthma control. 'Users' and 'non-users' of CM and CT were compared for characteristics of asthma, usage of conventional medications and parental demographics. RESULTS: One hundred and seventy-four children with 331 parents were enrolled in the study. All of the children were on bronchodilators and 150 (86.2%) were on disodium cromoglycate or inhaled steroids. Control was assessed by a physician as good in 95 children (54.6%), fair in 65 (37.4%) and poor or very poor in 13 (7.5%). Ninety (51.7%) of the children had used at least one CM in their lifetime. Out of the 145 preparations used, 90 (62.1%) were in current use. Vitamins and minerals (53.2%) and herbal preparations (29%) were used most commonly. Only 47.8% of parents had told their doctors about the use of CM. Costs ranged from $A2-$A200 (median $A10) per month. Forty-three (24.7%) of the children had been taken to an alternative practitioner at a cost of $A25-$A400 (median $A40) per month. Users of CM and CT were significantly more likely than non-users to have persistent asthma (P < 0.02), be on high-dose inhaled or oral steroids (P < 0.05), to have poor or very poor control of symptoms (P < 0.04), and more frequent doctor visits (P < 0.05). They also had more adverse reactions to relieving bronchodilators (P < 0.02) and were significantly older than non-users (P < 0.02). The most common reasons for using CM and CT were dissatisfaction with conventional therapies and concerns about steroid side-effects. CONCLUSIONS: Health professionals should be aware of the high rates of usage of CM and CT in asthmatic children and of parental attitudes to conventional and alternative therapies.

Administration, Inhalation↗
PubMed2001

Direct phosphorylation of NF-kappaB1 p105 by the IkappaB kinase complex on serine 927 is essential for signal-induced p105 proteolysis.

The p105 precursor protein of NF-kappaB1 acts as an NF-kappaB inhibitory protein, retaining associated Rel subunits in the cytoplasm of unstimulated cells. Tumor necrosis factor alpha (TNFalpha) and interleukin-1alpha (IL-1alpha) stimulate p105 degradation, releasing associated Rel subunits to translocate into the nucleus. By using knockout embryonic fibroblasts, it was first established that the IkappaB kinase (IKK) complex is essential for these pro-inflammatory cytokines to trigger efficiently p105 degradation. The p105 PEST domain contains a motif (Asp-Ser(927)-Gly-Val-Glu-Thr), related to the IKK target sequence in IkappaBalpha, which is conserved between human, mouse, rat, and chicken p105. Analysis of a panel of human p105 mutants in which serine/threonine residues within and adjacent to this motif were individually changed to alanine established that only serine 927 is essential for p105 proteolysis triggered by IKK2 overexpression. This residue is also required for TNFalpha and IL-1alpha to stimulate p105 degradation. By using a specific anti-phosphopeptide antibody, it was confirmed that IKK2 overexpression induces serine 927 phosphorylation of co-transfected p105 and that endogenous p105 is also rapidly phosphorylated on this residue after TNFalpha or IL-1alpha stimulation. In vitro kinase assays with purified proteins demonstrated that both IKK1 and IKK2 can directly phosphorylate p105 on serine 927. Together these experiments indicate that the IKK complex regulates the signal-induced proteolysis of NF-kappaB1 p105 by direct phosphorylation of serine 927 in its PEST domain.

Amino Acid Sequence↗
PubMed2001

Sizing short tandem repeat alleles in capillary array gel electrophoresis instruments.

A 96-capillary array gel electrophoresis Applied Biosystems 3700 instrument has been used to analyse AMPF/STR SGM Plus short tandem repeat (STR) loci for forensic applications. This multiplex consists of ten STR loci plus the Amelogenin locus and currently forms the basis of the UK National DNA database that currently holds more than 1 million profiles. Of particular interest is the accuracy of allele designation that is determined by comparison with standard control allelic ladder markers. Some loci have higher standard deviations than others. In particular the high-molecular-weight HUMFIBRA alleles have high standard deviations of the order of 0.15 and it is these alleles that are most likely to be misdesignated. However, this risk is minimised by the analysis of at least five different allelic ladders across the array to estimate the mean size of each allele. In conjunction with this, a series of guidelines that can be programmed into expert systems are used to minimise risks of misdesignation. The efficacy of the procedures utilised are tested by computer simulation and demonstrated to be robust.

Alleles↗
PubMed2001

"Porcine bronchus" diagnosed in neonatal period.

"Porcine bronchus" is a right upper lobe bronchus arising directly from the trachea. This is an infrequent congenital abnormality and it usually represents the displaced origin of a normal bronchus. We herewith report a case of a child who was diagnosed to have tracheal bronchus in neonatal period and followed subsequently until 13 months of age.

Bronchi↗
PubMed1999

Anti-dementia drugs.

Explore the source record for details and available documents.

Activities of Daily Living↗
PubMed1999

Neurological correlates of depressive symptoms in Alzheimer's disease and vascular dementia.

BACKGROUND: Organic brain disease such as dementia or stroke is associated with depression. In dementia, depressive symptoms are common where there is evidence of vascular disease and in Alzheimer's disease they often coexist with extrapyramidal signs. METHOD: In a study of 60 patients with Alzheimer's disease and 39 patients with vascular dementia, depressive symptoms were rated using the Cornell Scale for Depression in Dementia. Neurological signs were assessed and severity of cognitive impairment was measured with the Mini-Mental State Examination. RESULTS: Depressive symptoms were more severe in vascular dementia. Pyramidal tract signs had no relationship to depression in either type of dementia. In vascular dementia, extrapyramidal and grasp reflexes were strongly related to the severity of depression, and were associated with neurovegetative features. In Alzheimer's disease, extrapyramidal signs were the strongest independent predictor of the severity of depression. CONCLUSION: Depressive symptoms are more severe in vascular dementia compared to Alzheimer's disease and were related to neurological abnormalities.

Aged↗
PubMed1999

Children's fractures: a population based study.

OBJECTIVE: To measure the incidence of childhood fractures in a defined population. SETTING: Accident and emergency (A&E) departments covering the Swansea and Neath Port Talbot areas of South Wales in 1996. METHODS: Linkage of data from A&E departments with population data to produce fracture incidence rates by anatomical site and cause in children aged 0-14 years. RESULTS: During 1996, 2463 new fractures occurred in 2399 residents yielding a fracture rate of 36.1/1000 children. Fractures were more common in boys than girls and increased with age in both groups. Sports and leisure activities accounted for 36% of fractures, assaults for 3.5%, and road traffic accidents 1.4%. Fractures of the radius/ulna were most frequent (36%). CONCLUSIONS: The fracture rate in South Wales children is twice the rate reported in previous studies. Further research is required to elucidate the reasons behind this high rate. Many fractures could be prevented by the use of safer surfaces in school playgrounds, and wrist protection in in-line skaters and possibly in soccer players.

Adolescent↗
PubMed1999

Depressive symptoms and plan switching under managed care.

OBJECTIVE: A central assumption underlying managed care is that plan switching is a viable option for enrollees when they are dissatisfied. The authors used a national employee survey to test the hypothesis that this mechanism is less effective for enrollees with high levels of depressive symptoms than for the remainder of the population. METHOD: The study used data from the Employee Health Care Value Survey, a 1993 survey of 20,283 employees of three major corporations. The authors used the Medical Outcomes Study 36-Item Short-Form Health Survey to identify individuals with the highest decile of depressive and physical symptoms. They examined the relationship between symptoms and dissatisfaction and, for dissatisfied individuals, how symptoms predicted plan switching. Multivariate models were used to control for potential demographic, health, and health coverage confounders. RESULTS: Depressive and physical symptoms were both associated with dissatisfaction with care. Unlike physical symptoms, depressive symptoms were associated with a significantly lower likelihood of actually disenrolling among people who were dissatisfied or who intended to disenroll. This effect was most pronounced for satisfaction with administrative aspects of care (e.g., gatekeeping, utilization review). CONCLUSIONS: People with high levels of depressive symptoms appeared to be less willing or able to act on their dissatisfaction by switching plans. In particular, they were willing to tolerate higher rates of dissatisfaction with the administrative aspects of their health coverage without disenrolling. Plan switching is an essential mechanism underpinning a health care system predicated on competition; it may be less effective for people with depressive disorders.

Attitude to Health↗
PubMed1999

Parents' judgements about young children's problems: why mothers and fathers might disagree yet still predict later outcomes.

Correlates of parents' ratings of behavioural problems were explored in a sample of 93 British families, in which mothers and fathers rated their children at the time of the fourth birthday on the Achenbach Child Behavior Checklist. As in other samples, there was moderate convergence in mothers' and fathers' total problem scores, but also signs that they were reporting different sorts of problems linked to different influences. The father's rating was primarily associated with the child's cognitive ability. The mother's rating was primarily affected by her own mental state and view of her marriage. The father's but not the mother's rating provided unique information that predicted teachers' reports of the children's problems 7 years later. In general, parents' ratings of preschool children's problems reflect particular informants' perspectives on family life.

Affective Symptoms↗
PubMed1998

Brefeldin A-mediated apoptosis requires the activation of caspases and is inhibited by Bcl-2.

Brefeldin A (BFA) has recently been shown to induce apoptosis in human tumor cells in a p53-independent fashion. In this study, BFA-induced apoptosis was analyzed in the human Jurkat T-cell line. Apoptosis occurred 8 h after treatment with BFA and at concentrations as low as 10 ng/ml and increased with the duration of BFA exposure. Forskolin, an inhibitor of BFA-induced deaggregation of the Golgi-microtubular complex in some cell lines, failed to reverse BFA-mediated apoptosis. Further study of the mechanism of BFA-induced apoptosis was conducted by using a series of peptide protease inhibitors. Complete inhibition of cell death was achieved with benzyloxycarbonyl-Val-Ala-Asp-fluromethylketone, a peptide inhibitor of the caspase protease family, and Z-Asp-Glu-Val-Asp-FMK, a specific inhibitor of caspase-3. Both Acetyl-Tyr-Val-Ala-Asp-chloromethylketone and Acetyl-Tyr-Val-Ala-Asp-aldehyde, selective caspase-1 (interleukin-1beta converting enzyme) inhibitors, exerted only partial protection of cells from apoptosis at higher concentrations. Z-Phe-Ala-FMK, a cysteine protease inhibitor lacking aspartate at the P1 position, did not have any impact on BFA-induced apoptosis. Furthermore, Jurkat cells transfected with the proto-oncoprotein Bcl-2, which is able to block various apoptotic conditions, showed remarkable resistance to the apoptotic effect of BFA. Thus, the data indicate that BFA-induced apoptosis requires caspase(s) activation, primarily the activation of caspase-3, and is inhibited by overexpression of Bcl-2.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Caspase-mediated fragmentation of calpain inhibitor protein calpastatin during apoptosis.

Two cysteine protease families (caspase and calpain) participate in apoptosis. Here we report that the endogenous calpain inhibitor calpastatin is fragmented by caspase(s) to various extents during early apoptosis in two cell types. In anti-fas or staurosporine-treated Jurkat T-cells, the high-molecular-weight form (HMW) of calpastatin (apparent Mr 110 K) was extensively degraded to immunoreactive fragments of Mr 75 K and 30 K In apoptotic SH-SY5Y human neuroblastoma cells, HMW calpastatin was degraded to a major immunoreactive fragment of 75 K. In both cell types, fragmentation of HMW calpastatin was blocked by a caspase-specific inhibitor carbobenzoxy-Asp-CH2OC(O)-2,6-dichlorobenzene. In vitro translated HMW calpastatin was sensitive to proteolysis by recombinant caspase-1, -3, and -7. By contrast, in vitro translated LMW calpastatin (which lacks domains L and I) was cleaved into multiple fragments only by caspase-1 and was relatively resistant to caspase-3, -7, and other caspases tested. Consistently with that, purified erythroid LMW calpastatin was also highly susceptible to caspase-1 digestion. Recombinant human calpastatin spanning domain I through III (CAST(DI-III)) was found cleaved by caspase-1 at at least three sites, located in either the A or the C helix of domains I and III (ALDD137*L, LSSD203*F and ALAD404*S), while only a single site (ALDD137*L) was cleaved by caspase-3. These findings suggest that both HMW and LMW calpastatins are more vulnerable to caspase-1 than to caspase-3. Surprisingly, both erythroid LMW calpastatin and recombinant CAST(DI-III) fragmented by caspase-1 suffered only a less than twofold reduction of inhibitory activity toward calpain. We propose that the proteolysis of calpastatin in early apoptosis might have yet unidentified effects on the cross-talk between the two protease systems.

Apoptosis↗
PubMed1998

An adenoviral vector deleted for all viral coding sequences results in enhanced safety and extended expression of a leptin transgene.

Adenoviral (Ad)-mediated in vivo gene transfer and expression are limited in part by cellular immune responses to viral-encoded proteins and/or transgene immunogenicity. In an attempt to diminish the former responses, we have previously developed and described helper-dependent (HD) Ad vectors in which the viral protein coding sequences are completely eliminated. These HD vectors have up to 37 kb insert capacity, are easily propagated in a Cre recombinase-based system, and can be produced to high concentration and purity (>99.9% helper-free vector). In this study, we compared safety and efficacy of leptin gene delivery mediated by an HD vector (HD-leptin) and a first-generation E1-deleted Ad vector (Ad-leptin) in normal lean and ob/ob (leptin-deficient) mice. In contrast to evidence of liver toxicity, inflammation, and cellular infiltration observed with Ad-leptin delivery in mice, HD-leptin delivery was associated with a significant improvement in associated safety/toxicity and resulted in efficient gene delivery, prolonged elevation of serum leptin levels, and associated weight loss. The greater safety, efficient gene delivery, and increased insert capacity of HD vectors are significant improvements over current Ad vectors and represent favorable features especially for clinical gene therapy applications.

Adenoviridae↗
PubMed1998

Reduced quality of clot formation with gelatin-based plasma substitutes.

We have studied, over a wide range of dilutions using techniques of clot weight, thrombelastography and scanning electron microscopy, the physical properties of a blood clot formed in vitro when fresh blood was diluted with gelatin-based colloid solutions compared with crystalloid controls. The colloid solutions tested (3.5% polygeline (Haemaccel) and 4% succinylated gelatin (Gelofusine)) produced clots that had reduced median weight (P < 0.001 and P = 0.018, respectively) and reduced mean shear modulus (P < 0.001) compared with crystalloid controls. Scanning electron microscopy showed that the fibrin formed a less extensive mesh in the presence of the gelatin-based colloids compared with crystalloid. Reduction in clot quality with gelatin-based colloids has not been noted previously and further work is needed to ascertain if this occurs in vivo as these solutions are used frequently in patients who require full haemostatic competence.

Blood Cells↗