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Biomedical subjects

D Allen

Publications and source records attributed to D Allen.

At least 37 records · Page 2Linked to original sources
PubMed2002

Sedation effects on responsiveness: evaluating the reduction of antipsychotic medication in people with intellectual disability using a conditional probability approach.

BACKGROUND: The impact of the withdrawal of long-term antipsychotic medication prescribed to adults with intellectual disabilities on behavioural functioning has been investigated using a real-time direct observation methodology. Previous authors have reported a significant post-reduction difference in engagement in activity between the successful drug reduction and control groups. METHOD: In the present study, sequential analysis of the relationship between staff:resident interaction and behavioural engagement was used to give a more precise measure of the extent to which user responsiveness is affected by drug withdrawal. Responsiveness was measured by calculating the likelihood of engagement occurring given the occurrence of staff interaction. This likelihood was represented by the statistic Yule's Q-value. RESULTS: High Yule's Q-value results pre- and post-baseline were found, indicating that clients were highly responsive to staff interaction. However, Yule's Q-value did not significantly increase following drug withdrawal. CONCLUSION: The present study provides no evidence of greater responsiveness following the withdrawal of psychotropic medication.

Adult↗
PubMed2002

Sternal osteomyelitis caused by Aspergillus fumigatus in a patient with previously treated Hodgkin's disease.

This report details the case of a 67 year old woman with sternal osteomyelitis caused by Aspergillus fumigatus. She was diagnosed with Hodgkin's disease in 1975 and was successfully treated with chemotherapy. A lobectomy for recurrence localised to the left lung was complicated nine years later by severe bronchiectasis, for which she required a total left sided pneumonectomy. At surgery, a non-invasive aspergillus was found. She presented eight years later with symptoms that were initially attributed to recurrence of Hodgkins's disease, but on investigation were found to be caused by fungal sternal osteomyelitis. Treatment with itraconazole suspension at a dose of 400 mg daily was successful.

Aged↗
PubMed2001

Workforce planning. Of one mind.

The NHS is heavily reliant on locum doctors, many of whom trained overseas. It is important they are appropriately trained so they can be integrated into the workforce. A pilot nine-session course for consultant locum psychiatrists was well received by participants. Medical directors have expressed willingness to pay for locums to attend such courses.

Clinical Competence↗
PubMed2001

Development of serine protease inhibitors displaying a multicentered short (<2.3 A) hydrogen bond binding mode: inhibitors of urokinase-type plasminogen activator and factor Xa.

Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazole-5-carboxamidine, 6b, which is known to display several modes of binding. For instance, 6b can recruit zinc and bind in a manner similar to that reported by bis(5-amidino-2-benzimidazolyl)methane (BABIM) (Nature 1998, 391, 608-612).(1) Alternatively, 6b can bind in the absence of zinc through a multicentered network of short (<2.3 A) hydrogen bonds. The lead structure was optimized in the zinc-independent binding mode toward a panel of six human serine proteases to yield optimized inhibitors such as 2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine, 22a, and 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine, 22f. Structure-activity relationships determined that, apart from the amidine function, an indole or benzimidazole and an ortho substituted phenol group were also essential components for optimal potency. The affinities (K(i)) of 22a and 22f, for example, bearing these groups ranged from 8 to 600 nM toward a panel of six human serine proteases. High-resolution crystal structures revealed that the binding mode of these molecules in several of the enzymes was identical to that of 6b and involved short (<2.3 A) hydrogen bonds among the inhibitor hydroxyl oxygen, Ser195, and a water molecule trapped in the oxyanion hole. In summation, novel and potent trypsin-like serine protease inhibitors possessing a unique mode of binding have been discovered.

Amidines↗
PubMed2001

Phantom limb pain and residual limb pain following lower limb amputation: a descriptive analysis.

PURPOSE: This research aimed to develop a clearer picture of the experience of residual limb pain and phantom limb pain following a lower limb amputation and to gain a greater understanding of their relationships with physical and psychosocial variables. METHOD: One hundred and four participants completed the Trinity Amputation and Prosthesis Experience Scales (TAPES), which includes a section on each of, psychosocial issues, activity restriction, satisfaction with a prosthesis and pain (incidence, duration, level and extent of interference). RESULTS: The results showed that 48.1% of the sample experienced residual limb pain and 69.2% experienced phantom limb pain. While fewer people experienced residual limb pain, those who did, experienced it for longer periods, at a greater level of intensity and with a greater amount of interference in their daily lifestyle, than people who were experiencing phantom limb pain. The experience of residual limb pain was associated with other medical problems and low levels of Adjustment to Limitation. Phantom limb pain was associated with older age, being female, above knee amputation, causes other than congenital causes, not receiving support prior to the amputation, the experience of other medical problems, low scores on Adjustment to Limitation and high scores on Aesthetic Satisfaction with the prosthesis. CONCLUSION: These findings provide a greater understanding of the issues to be taken into consideration in the rehabilitation of people with a lower limb amputation.

Adolescent↗
PubMed2001

Repetitive high-dose topotecan, carboplatin, and paclitaxel with peripheral blood progenitor cell support in previously untreated ovarian cancer: results of a Phase I study.

OBJECTIVE: In view of the significant activity of topotecan in ovarian cancer with dose-limiting toxicity (DLT) of myelosuppression, we evaluated the addition of topotecan to carboplatin and paclitaxel with peripheral blood progenitor cell (PBPC) support. METHODS: Patients with previously untreated stage IIIC or IV ovarian cancer with macroscopic residual disease following primary debulking surgery were eligible. Patients received two cycles of carboplatin AUC = 5 and 175 mg/m(2) of paclitaxel with collection of PBPCs after the second cycle. Patients subsequently received three cycles of high-dose therapy (HDT) with topotecan on a daily x5 schedule, paclitaxel (250 mg/m(2) over 24 h), and carboplatin (AUC = 12-16). RESULTS: Nineteen patients with a median age of 49 years (range 21-63) were enrolled and topotecan was escalated in 6 patient cohorts up to a dose of 4.5 mg/m(2)/day. Fifty-two of the planned 57 treatment cycles were delivered with no treatment-related deaths. Neutrophil and platelet recovery was rapid and the interval between HDT was 28 days. Febrile neutropenia occurred following 57% of all HDT cycles. DLTs of mucositis and diarrhea were observed at topotecan (4.5 mg/m(2)/day), paclitaxel (250 mg/m(2)) and carboplatin (AUC = 12). The protocol was subsequently modified to administer topotecan (2.5 mg/m(2)/day) with carboplatin (AUC = 16); however, 2 patients developed grade 4 diarrhea (1 with grade 3 mucositis and 1 with grade 4 mucositis). The clinical CR rate was 73% (14/19) with an overall clinical response rate of 95% (18/19). Of the 14 patients with a CCR, 13 of these underwent a second-look laparotomy with 8 (61%) achieving a pathological CR. With a median follow-up of 28 months (range 11-40 months), the median PFS is 36 months and OS has not been reached. CONCLUSION: When combined with carboplatin (AUC = 12) and paclitaxel (250 mg/m(2)), the recommended topotecan dose is 3.5 mg/m(2)/day for 5 days. This outpatient HDT regimen combines three of the most active drugs in ovarian cancer with acceptable toxicity and promising activity.

Adult↗
PubMed2001

Engineering inhibitors highly selective for the S1 sites of Ser190 trypsin-like serine protease drug targets.

BACKGROUND: Involved or implicated in a wide spectrum of diseases, trypsin-like serine proteases comprise well studied drug targets and anti-targets that can be subdivided into two major classes. In one class there is a serine at position 190 at the S1 site, as in urokinase type plasminogen activator (urokinase or uPA) and factor VIIa, and in the other there is an alanine at 190, as in tissue type plasminogen activator (tPA) and factor Xa. A hydrogen bond unique to Ser190 protease-arylamidine complexes between O gamma(Ser190) and the inhibitor amidine confers an intrinsic preference for such inhibitors toward Ser190 proteases over Ala190 counterparts. RESULTS: Based on the structural differences between the S1 sites of Ser190 and Ala190 protease-arylamidine complexes, we amplified the selectivity of amidine inhibitors toward uPA and against tPA, by factors as high as 220-fold, by incorporating a halo group ortho to the amidine of a lead inhibitor scaffold. Comparison of K(i) values of such halo-substituted and parent inhibitors toward a panel of Ser190 and Ala190 proteases demonstrates pronounced selectivity of the halo analogs for Ser190 proteases over Ala190 counterparts. Crystal structures of Ser190 proteases, uPA and trypsin, and of an Ala190 counterpart, thrombin, bound by a set of ortho (halo, amidino) aryl inhibitors and of non-halo parents reveal the structural basis of the exquisite selectivity and validate the design principle. CONCLUSIONS: Remarkable selectivity enhancements of exceptionally small inhibitors are achieved toward the uPA target over the highly similar tPA anti-target through a single atom substitution on an otherwise relatively non-selective scaffold. Overall selectivities for uPA over tPA as high as 980-fold at physiological pH were realized. The increase in selectivity results from the displacement of a single bound water molecule common to the S1 site of both the uPA target and the tPA anti-target because of the ensuing deficit in hydrogen bonding of the arylamidine inhibitor when bound in the Ala190 protease anti-target.

Animals↗
PubMed2001

Predictors and correlates of adaptive functioning in children with developmental disorders.

Autism is a developmental disorder marked by impairments in socialization, communication, and perseverative behavior and is associated with cognitive impairment and deficits in adaptive functioning. Research has consistently demonstrated that children with autism have deficits in adaptive functioning more severe than their cognitive deficits. This study investigates the correlates and predictors of adaptive functioning as measured by the Vineland Adaptive Behavior Scales in high- and low-functioning children with autism and their age and nonverbal IQ matched controls. Thirty-five 9-year-old children with high-functioning autism (HAD) were compared with 31 age-matched children with developmental language disorder (DLD), and 40 9-year-old children with low-functioning autism (LAD) were compared with 17 age-matched children with low IQ on adaptive functioning, IQ, autistic symptomology, and tests of language and verbal memory. Results indicate that both groups with autism were significantly impaired compared to their matched controls on Socialization and Daily Living, but not Communication and that these impairments were more pronounced in the HAD group than in the LAD group. Adaptive behavior was strongly correlated with autistic symptomology only in the HAD group. Regression analyses indicated that IQ was strongly predictive of adaptive behavior in both low-functioning groups, but tests of language and verbal memory predicted adaptive behavior in the higher functioning groups. Results suggest that IQ may act as a limiting factor for lower functioning children but higher functioning children are impaired by specific deficits, including autistic symptomology and impaired language and verbal memory.

Adaptation, Psychological↗
PubMed2001

Differences in nicotine-induced dopamine release and nicotine pharmacokinetics between Lewis and Fischer 344 rats.

Studies have shown a greater preference for the self-administration of drugs such as nicotine and cocaine in the Lewis rat strain than in the Fischer 344 strain. We examined some factors that could contribute to such a difference. The baseline level of extracellular dopamine in nucleus accumbens shell was about 3-times higher in Fischer rats than in Lewis rats (3.18 +/- 0.26 vs. 1.09 +/- 0.14 pg/ sample). Nicotine (50-100 microg/kg)-induced release of dopamine, expressed in absolute terms, was similar in the two strains. Dopamine release expressed in relative terms (as percent of baseline), however, was significantly greater in Lewis rats than in Fischer rats at 30 min after the first nicotine injection. We suggest that the relative increase is of more influence than the absolute level for determining preference; a lower physiological extracellular dopamine level thus represent a risk factor for increased preference. Amphetamine-induced dopamine release expressed in relative terms was not greater in the Lewis strain. In the initial time period of the microdialysis experiments, a sharper peak in nicotine-induced accumbal dopamine release in Lewis and a less but more sustained release in Fischer rats was observed. This release pattern paralleled the faster clearance of nicotine from blood of Lewis compared to Fischer rats. In tissue slices the electrically induced dopamine release was highest in the nucleus accumbens and lowest in the ventral tegmentum. A significant effect of nicotine was lowering the electrically induced release of dopamine in frontal cortex slices from Fischer brain and increasing this dopamine release in the ventral tegmentum of Lewis brain slices indicating that the ventral tegmentum, an area controlling dopamine release in the accumbens, is more responsive to nicotine in the Lewis rat. Nicotine levels tended to be more sustained in Fischer rats in different brain regions, although the difference in nicotine levels between the strains was not significant at any time period. Several factors contribute to nicotine preference, including the endogenous dopamine level, and the sensitivity of ventral tegmentum neurons to nicotine-induced dopamine release. Strain differences in pharmacokinetics of nicotine may also play a role.

Animals↗
PubMed2001

Assessing the need for reactive behaviour management strategies in children with intellectual disability and severe challenging behaviour.

The need for reactive behavioural management strategies for aggressive behaviours in adults with intellectual disability has been clearly established, but equivalent information concerning children with challenging behaviour is lacking by comparison. The present study was conducted in order to assess this need. A retrospective study was conducted to ascertain the nature of aggressive behaviours amongst a cohort children referred to a specialist support service. Aggressive behaviours were found to occur at high rates within the study group. Almost 60% of the children displayed aggression that occurred at least daily, and the behaviours resulted in serious consequences for carers in almost one-third of the group. Physical interventions were already in use in 56% of cases, but were largely improvised by carers. The need to include reactive behavioural training as part of an overall intervention package for carers of children with challenging behaviour appeared to be supported by the present results. The implications for training design are discussed.

Adolescent↗
PubMed2001

The implications of healthcare reforms for the profession of nursing.

This paper offers a wide-ranging analysis of concerns that the value of emotion work within nursing is being eroded. We examine the occupation's historical development to argue that, in so far as emotion work has any essence within nursing, it is as an occupational myth which has been deployed to legitimate nurses' jurisdictional claims. We argue that recent developments in health-care raise questions about the benefits of claims of this kind and suggest that a little more realism about the nature of nursing work might make for a more sustainable professional future.

Cost Control↗
PubMed2001

Effects of land use data on dry deposition in a regional photochemical model for eastern Texas.

Land use data are among the inputs used to determine dry deposition velocities for photochemical grid models such as the Comprehensive Air Quality Model with extensions (CAMx) that is currently used for attainment demonstrations and air quality planning by the state of Texas. The sensitivity of dry deposition and O3 mixing ratios to land use classification was investigated by comparing predictions based on default U.S. Geological Survey (USGS) land use data to predictions based on recently compiled land use data that were collected to improve biogenic emissions estimates. Dry deposition of O3 decreased throughout much of eastern Texas, especially in urban areas, with the new land use data. Predicted 1-hr averaged O3 mixing ratios with the new land use data were as much as 11 ppbv greater and 6 ppbv less than predictions based on USGS land use data during the late afternoon. In addition, the area with peak O3 mixing ratios in excess of 100 ppbv increased significantly in urban areas when deposition velocities were calculated based on the new land use data. Finally, more detailed data on land use within urban areas resulted in peak changes in O3 mixing ratios of approximately 2 ppbv. These results indicate the importance of establishing accurate, internally consistent land use data for photochemical modeling in urban areas in Texas. They also indicate the need for field validation of deposition rates in areas experiencing changing land use patterns, such as during urban reforestation programs or residential and commercial development.

Agriculture↗
PubMed2001

Expression of interleukin-1beta in the digital laminae of horses in the prodromal stage of experimentally induced laminitis.

OBJECTIVE: To study expression of interleukin-1beta (IL-1beta) in the digital laminae of horses in the prodromal stage of experimentally induced laminitis. ANIMALS: 8 healthy adult horses with no signs of laminitis. PROCEDURES: Black walnut extract was administered via nasogastric tube to 4 horses, and water was administered to the remaining 4 (controls). Complete blood counts and physical examinations were performed every 30 minutes after administration of black walnut extract or water. General anesthesia was induced when total WBC count decreased by 30% in horses given the black walnut extract and 3 hours after water administration in control horses. The left forefoot was perfusion fixed with neutral-buffered 10% formalin, and paraffin-embedded sections of the digit were used for in situ hybridization with an equine-specific IL-1beta probe. RESULTS: IL-1beta mRNA expression was observed in perivascular cells of the small laminar venules and capillaries in all 4 horses given black walnut extract and in interstitial cells remote from the microvasculature in 1 of the 4. Other cellular components of the laminar tissue and cellular components of the digital arterioles and veins did not exhibit IL-1beta mRNA expression. Expression of IL-1beta mRNA was not detected in laminae from control horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that IL-1beta mRNA is expressed by perivascular cells in the laminar tissues of horses in the prodromal stage of experimentally induced laminitis. This provides evidence of an inflammatory process during the prodromal stage of laminitis, indicating that local digital proinflammatory cytokine expression may be an initiating factor in laminitis.

Animals↗
PubMed2001

Life after a stroke.

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Activities of Daily Living↗