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1.
Br J Oral Maxillofac Surg ; 62(2): 157-163, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38238115

ABSTRACT

The nationwide extension of the electric scooter (e-scooter) scheme, which began in 2020, aimed to alleviate public transport congestion, to reduce pollution and peak-time road traffic. This retrospective study evaluates the range of e-scooter-related maxillofacial trauma before the recent scheme extension and compares the findings with existing literature on this topic. The Queen Elizabeth Hospital Birmingham, United Kingdom (UK) operates as a Level 1 Regional Major Trauma Centre and serves a population of four million. All patient records between September 2021 to September 2022 were analysed to establish the types of e-scooter-related maxillofacial trauma sustained. A Pearson's chi-squared test was used to assess for significant associations between variables recorded. Falls accounted for the majority of injuries (44.3%), and soft tissue lacerations were the most common maxillofacial injury (38%). Statistically significant results were measured in the following variables: gender and intoxication status (p = 0.007), helmet status and injuries sustained in maxillofacial and non-maxillofacial regions (p = 0.043), mechanism of injury and injuries sustained in both the maxillofacial and non-maxillofacial regions (p = 0.045). E-scooters are an emerging concern within the UK. Further studies across the UK are required to assess the frequency of e-scooter-related injuries. Such data may prove useful in determining the government's decision on e-scooter use on UK roads.


Subject(s)
Head , Maxillofacial Injuries , Humans , Retrospective Studies , Head Protective Devices , Maxillofacial Injuries/epidemiology , Maxillofacial Injuries/etiology , United Kingdom/epidemiology
2.
In. Faculty of Medical Sciences, The University of the West Indies. 2020 National Health Research Conference: Advancing Health Research in Trinidad and Tobago. Port of Sapin, Caribbean Medical Journal, November 19, 2020. .
Non-conventional in English | MedCarib | ID: biblio-1353744

ABSTRACT

Lung cancer is one of the most common cause of mortality, highly attributed to an increase in tobacco use/ cigarette smoking. It ranks amongst the top 3 causes of cancer in Trinidad and Tobagonian men. The objective of this study is to the investigate the prevalence of Lung cancer in Trinidad and Tobago, its histological subtypes, demographics, predisposing risk factors and presenting stage. Additionally, comparison is made between current Lung cancer trends and those identified from previous studies. Our current findings is a more accurate representation of local trends, which can now provide foundational data that can be used to implement better approaches in the improvement of Lung cancer care in Trinidad and Tobago.


Subject(s)
Humans , Male , Trinidad and Tobago , Lung Neoplasms , Risk Factors , Mortality , Cigarette Smoking
4.
Diabet Med ; 36(3): 376-382, 2019 03.
Article in English | MEDLINE | ID: mdl-30264906

ABSTRACT

AIM: To explore the dose-response between frequency of interruption of sedentary time and basal glucose (fasting glucose, the dawn phenomenon and night-time glucose) in Type 2 diabetes. METHODS: In a randomized three-treatment, two-period balanced incomplete block trial, 12 people with Type 2 diabetes (age, 60.0 ± 3.2 years; BMI, 30.2 ± 1.4 kg/m2 ) completed two of three conditions: sitting for 7 h interrupted every 60 min (Condition 1), 30 min (Condition 2), and 15 min (Condition 3) by 3-min light-intensity walking breaks. The activPAL3 and FreeStyle Libre were used to assess physical activity/sedentary behaviour and continuous glucose profile. Standardized meals were provided, and changes in basal glucose of the nights and early mornings before and after treatment conditions were calculated (mean ± SE). RESULTS: After treatment conditions, fasting glucose and duration of the dawn phenomenon were lower for Condition 3 (-1.0 ± 0.2 mmol/l, P < 0.02; -3.1 ± 1.3 h, P = 0.004) compared with Condition 1 (-0.1 ± 0.2 mmol/l; 1.9 ± 1.2 h). The magnitude of the dawn phenomenon was reduced in Condition 3 (-0.6 ± 0.4 mmol/l, P = 0.041) compared with Condition 2 (0.6 ± 0.3 mmol/l). Night-time glycaemic variability (coefficient of variation) was reduced in Condition 3 (-9.7 ± 3.9%) relative to Condition 2 (6.1 ± 4.8%, P < 0.03) and Condition 1 (2.5 ± 1.8%, P = 0.02). There was no change in night-time mean glucose. CONCLUSIONS: Frequent interruptions of prolonged sitting with 3 min of light-intensity walking breaks every 15 min improves fasting glucose, the dawn phenomenon and night-time glycaemic variability, and this might be a simple therapeutic intervention to improve glucose control. Clinicaltrials.gov Identifier: NCT02738996.


Subject(s)
Blood Glucose/metabolism , Circadian Rhythm/physiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/therapy , Exercise/physiology , Sedentary Behavior , Aged , Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 2/physiopathology , Fasting/blood , Female , Humans , Male , Middle Aged , Postprandial Period , Time Factors , Walking/physiology
6.
Br J Oral Maxillofac Surg ; 56(6): 496-500, 2018 07.
Article in English | MEDLINE | ID: mdl-29735181

ABSTRACT

Major trauma is an important cause of mortality and morbidity worldwide. Mortality is high with rates over 10% commonly reported. We studied the epidemiology and aetiology of maxillofacial injuries in patients who presented with major trauma as recorded nationally by retrospectively analysing the database of the Trauma Audit Research Network from 2001 to 2015. All patients who had major trauma with associated maxillofacial injuries were included in the analysis. Of 104645 patients recorded as having had major trauma during the study period, 22148 (21.2%) had an associated maxillofacial injury. Most of them were male (74.2%), and the type of injury was usually blunt (97.5%). Road traffic collisions were the most common mechanism (44.1%), followed by falls of less than 2m (21.6%). An associated serious head injury was more common in those who had a facial injury (81% compared with 60.6%, p<0.0001). Nearly all the facial injuries (94%) were minor, or moderately severe. Maxillofacial injuries commonly present with major trauma but are rarely severe. A maxillofacial injury may indicate an increased likelihood of an associated head injury.


Subject(s)
Maxillofacial Injuries/epidemiology , Maxillofacial Injuries/etiology , Adult , Aged , England/epidemiology , Female , Humans , Injury Severity Score , Male , Middle Aged , Multiple Trauma , Retrospective Studies , Wales/epidemiology
7.
Brain Behav Immun ; 68: 98-110, 2018 02.
Article in English | MEDLINE | ID: mdl-29030217

ABSTRACT

When facial nerve axotomy (FNA) is performed on immunodeficient recombinase activating gene-2 knockout (RAG-2-/-) mice, there is greater facial motoneuron (FMN) death relative to wild type (WT) mice. Reconstituting RAG-2-/- mice with whole splenocytes rescues FMN survival after FNA, and CD4+ T cells specifically drive immune-mediated neuroprotection. Evidence suggests that immunodysregulation may contribute to motoneuron death in amyotrophic lateral sclerosis (ALS). Immunoreconstitution of RAG-2-/- mice with lymphocytes from the mutant superoxide dismutase (mSOD1) mouse model of ALS revealed that the mSOD1 whole splenocyte environment suppresses mSOD1 CD4+ T cell-mediated neuroprotection after FNA. The objective of the current study was to characterize the effect of CD4+ T cells on the central molecular response to FNA and then identify if mSOD1 whole splenocytes blocked these regulatory pathways. Gene expression profiles of the axotomized facial motor nucleus were assessed from RAG-2-/- mice immunoreconstituted with either CD4+ T cells or whole splenocytes from WT or mSOD1 donors. The findings indicate that immunodeficient mice have suppressed glial activation after axotomy, and cell transfer of WT CD4+ T cells rescues microenvironment responses. Additionally, mSOD1 whole splenocyte recipients exhibit an increased astrocyte activation response to FNA. In RAG-2-/- + mSOD1 whole splenocyte mice, an elevation of motoneuron-specific Fas cell death pathways is also observed. Altogether, these findings suggest that mSOD1 whole splenocytes do not suppress mSOD1 CD4+ T cell regulation of the microenvironment, and instead, mSOD1 whole splenocytes may promote motoneuron death by either promoting a neurotoxic astrocyte phenotype or inducing Fas-mediated cell death pathways. This study demonstrates that peripheral immune status significantly affects central responses to nerve injury. Future studies will elucidate the mechanisms by which mSOD1 whole splenocytes promote cell death and if inhibiting this mechanism can preserve motoneuron survival in injury and disease.


Subject(s)
CD4-Positive T-Lymphocytes/physiology , Facial Nerve/immunology , Facial Nerve/physiology , Amyotrophic Lateral Sclerosis/immunology , Animals , Axotomy/methods , CD4-Positive T-Lymphocytes/immunology , Cell Death/physiology , Cell Survival/physiology , DNA-Binding Proteins/genetics , DNA-Binding Proteins/physiology , Disease Models, Animal , Facial Nerve Injuries , Facial Nucleus , Female , Mice , Mice, Inbred C57BL , Motor Neurons/immunology , Neuroprotection , Spleen/immunology , Superoxide Dismutase/genetics
8.
Int J Oral Maxillofac Surg ; 42(11): 1414-7, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23932579

ABSTRACT

The use of composite radial free tissue transfer has been overtaken by other composite flaps. This is due to donor site morbidity and the poor volume of bone yielded. The advantages and potential complications of composite radial flaps are well described. Use of the composite radial forearm free flap has been largely superseded in mandible reconstruction, but applications such as a salvage option still exist. Additionally it may be used in the reconstruction of midface defects. The use of a cutting guide to reduce the donor site complications and yet produce a maximal yield of bone is described herein. With the use of a skilled maxillofacial laboratory, the planning allows precise cuts and placement of the free flap and allows accurate prophylactic plating of the radius. A precise titanium cutting guide and custom distal radius plate are used. Details of three cases where these techniques have been implemented are described. The paper demonstrates the significant advantages of using laboratory-based technology to assist in performing composite radial free flaps. This paper reveals that composite radial free tissue transfer still has a place in the reconstruction of very selective defects of the head and neck. In particular, its use in reconstruction of Class 5 and 6 maxillary defects (Brown classification) is illustrated. Correct case selection and planning results in increased confidence to use this flap.


Subject(s)
Bone Transplantation/methods , Composite Tissue Allografts/transplantation , Free Tissue Flaps/transplantation , Orthognathic Surgical Procedures , Plastic Surgery Procedures/methods , Radius/surgery , Humans , Plastic Surgery Procedures/instrumentation , Titanium
9.
Int J Obes (Lond) ; 31(8): 1334-6, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17310220

ABSTRACT

Obesity and diabetes are serious health problems for Americans and especially for those with American Indian or Mexican ancestry. A preliminary survey by protein analysis rather than classical nucleic acid sequencing methods has suggested a correlation between a newly discovered T45S variant of apolipoprotein C1 (ApoC1), found only in persons with American Indian or Mexican ancestry, and elevated body mass index (BMI). American Indians with the S45 ApoC1 variant (n=36) had an average of 9% higher BMI than those who had only T45 ApoC1 (n=192, P=0.029). Elevated rates of diabetes were reported for parents of subjects with the S45 protein (P=0.006). In five gender-matched sibling pairs, persons with Mexican ancestry showed a 1.34-fold higher BMI for those with S45 ApoC1 (P=0.022). This protein may contribute to the elevated rates of diabetes in relevant ethnic groups and might be more common in isolated populations.


Subject(s)
Apolipoprotein C-I/genetics , Body Mass Index , Hispanic or Latino/genetics , Indians, North American/genetics , Adult , DNA/genetics , Diabetes Mellitus/ethnology , Diabetes Mellitus/genetics , Female , Genetic Variation/genetics , Hispanic or Latino/ethnology , Humans , Indians, North American/ethnology , Male , Middle Aged , Obesity/genetics , Prevalence , Sequence Analysis, DNA , United States
10.
Comput Biol Med ; 36(3): 262-75, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16446160

ABSTRACT

John Tukey used the term exploratory data analysis (EDA) to describe a philosophy for analyzing data where graphical and numerical summaries are used to uncover interesting structures. The applied statistician today has a much more sophisticated set of methods to use when applying the EDA philosophy. One such collection of methods is functional data analysis (FDA), which was used to explore the structure of lactate curves. A principal components analysis and plots of the second derivatives provide new intuitive endurance markers which correlates highly with other numerical summaries of lactate curves that have been suggested in the literature.


Subject(s)
Lactic Acid/blood , Models, Biological , Principal Component Analysis , Humans , Male , Physical Endurance , Soccer
11.
Br J Sports Med ; 39(7): 432-6, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15976165

ABSTRACT

OBJECTIVE: To examine the changes in aerobic endurance performance of professional youth soccer players throughout the soccer season. METHODS: Nine youth soccer players were tested at six different time points throughout the soccer season by sub-maximal blood lactate assessment, using an incremental treadmill protocol. Whole blood lactate concentration and heart frequency (Hf) were determined at each exercise stage. Running velocities at the first lactate inflection point (v-T(lac)) and at a blood lactate concentration of 4 mmol l(-1) (v-4mM) were determined. RESULTS: Running velocity at the two lactate thresholds increased from the start of pre-season training to the early weeks of the competitive season, from 11.67 (0.29) to 12.96 (0.28) km h(-1) for v-T(lac), and from 13.62 (0.25) to 14.67 (0.24) km h(-1) for v-4mM (p<0.001). However, v-T(lac )and v-4mM when expressed relative to maximum heart frequency (Hf(max)) remained unchanged. The Hf to blood lactate concentration relationship was unchanged after the pre-season training period. The two expressions of lactate threshold did not reveal differences between each other. CONCLUSION: Running velocity at v-T(lac )and v-4mM increased significantly over the pre-season period, but v-T(lac )and v-4mM were unchanged when expressed relative to Hf(max). This finding may indicate that increased endurance performance may be mainly attributable to alterations in Vo(2max). Although lactate assessment of soccer players is useful for determining endurance training adaptations in soccer players, additional assessment of the other two determinants of endurance performance (Vo(2max) and running economy) may provide more useful information for determining physiological adaptations resulting from soccer training and training interventions.


Subject(s)
Heart Rate/physiology , Lactic Acid/blood , Soccer/physiology , Adolescent , Exercise Test/methods , Humans , Oxygen Consumption/physiology , Physical Education and Training/methods , Physical Endurance/physiology , Time Factors
12.
Br J Sports Med ; 39(5): 273-7, 2005 May.
Article in English | MEDLINE | ID: mdl-15849290

ABSTRACT

BACKGROUND: Improved oxygen uptake improves soccer performance as regards distance covered, involvements with the ball, and number of sprints. Large improvements in oxygen uptake have been shown using interval running. A similar physiological load arising from interval running could be obtained using the soccer ball in training. OBJECTIVES: The main aim was to study physiological adaptations to a 10 week high intensity aerobic interval training program performed by professional youth soccer players, using a soccer specific ball dribbling track. METHODS: Eleven youth soccer players with a mean (SD) age of 16.9 (0.4) years performed high intensity aerobic interval training sessions twice per week for 10 weeks in addition to normal soccer training. The specific aerobic training consisted of four sets of 4 min work periods dribbling a soccer ball around a specially designed track at 90-95% of maximal heart frequency, with a 3 min recovery jog at 70% of maximal heart frequency between intervals. RESULTS: Mean VO2max improved significantly from 63.4 (5.6) to 69.8 (6.6) ml kg(-1) min(-1), or 183.3 (13.2) to 201.5 (16.2) ml kg(-0.75) min(-1) (p<0.001). Squat jump and counter movement jump height increased significantly from 37.7 (6.2) to 40.3 (6.1) cm and 52.0 (4.0) to 53.4 (4.2) cm, respectively (p<0.05). No significant changes in body mass, running economy, rate of force development, or 10 m sprint times occurred. CONCLUSION: Performing high intensity 4 min intervals dribbling a soccer ball around a specially designed track together with regular soccer training is effective for improving the VO2max of soccer players, with no negative interference effects on strength, jumping ability, and sprinting performance.


Subject(s)
Adaptation, Physiological/physiology , Oxygen Consumption/physiology , Soccer/physiology , Adolescent , Exercise Tolerance/physiology , Humans , Male , Physical Education and Training/methods , Physical Endurance/physiology , Physical Fitness/physiology , Running/physiology , Task Performance and Analysis , Track and Field/physiology
13.
Eur J Appl Physiol ; 87(2): 159-66, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12070627

ABSTRACT

The aim of this study was to investigate the reproducibility of blood lactate measurements, heart rate (HR) and ratings of perceived exertion (RPE) during treadmill exercise at speeds corresponding to the lactate threshold ( v(Th,la)-) and a fixed blood lactate concentration of 4 mmol.l(-1)( v(la)-(,4)). Possible differences in reproducibility related to fitness levels were also investigated. A group of 20 men [mean (SD)] [age 20.5 (1.4) years] and 16 women [age 21.2 (0.9) years] took part in the study. The subjects performed two identical incremental exercise tests consisting of at least six 4 min stages. Blood lactate concentrations, HR and RPE were recorded at the end of each stage. Limits of agreement (LoA), correlation coefficients and 95% confidence intervals for the mean difference between tests were employed to investigate the level of agreement and reproducibility of blood lactate concentration, HR and RPE. For the group as a whole, the sample correlation coefficient for speed at v(Th,la)- was r=0.88, and was r=0.92 for the speed at v(la)-(,4). At v(Th,la) -, the correlation coefficients for the moderately fit and unfit were r=0.94 and r=0.36, respectively, and at v(la)-(,4) r=0.93 and r=0.68, respectively. The LoA for the moderately fit group indicated that a change of 1.62 km.h(-1) in v(Th,la)- would be necessary to be considered a change in training status. For HR and RPE, relationships between the tests were generally poor. The LoA suggested that changes in scores must be unacceptably large. These findings cast doubt on the sensitivity of testing for change of blood lactate concentration, HR and RPE in this population.


Subject(s)
Exercise Test , Heart/physiology , Lactic Acid/blood , Perception/physiology , Physical Exertion/physiology , Adult , Exercise/physiology , Exercise/psychology , Female , Heart Rate , Humans , Male , Reproducibility of Results , Sensitivity and Specificity , Statistics as Topic
14.
J Neurosci Methods ; 109(1): 59-70, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11489301

ABSTRACT

Recently, voltammetry with carbon fibre electrodes (CFE) has been implemented for real time measurement of nitrogen monoxide (NO) indicating that it is oxidised at the potential value of nitrites, approximately +700 mV. In contrast, here we show that modified CFE can monitor NO at oxidation potentials different than that of nitrites, i.e. +550 mV. Indeed, at +550 mV a significant increase of amperometric current levels was obtained when NO but not nitrites, were added to a phosphate buffer saline solution (PBS). Differential pulse voltammetry (DPV) supports these findings as two oxidation peaks were obtained when examining air preserved NO; peak 1 at +550 mV and peak 2 at +700 mV, respectively. In contrast, only peak 2 was monitored when nitrites or a solution of NO oxidised in air was added to PBS. Biological support to these in vitro data comes from the observation that the relaxation of an adrenaline-contracted aortic ring produced via addition of NO is concomitant with peak 1 at +550 mV. The relaxation is almost completed before the appearance of peak 2 at +700 mV. Furthermore, in vivo experiments performed in the striatum of rats show that the amperometric signal monitored at +550 mV is responsive to glutamatergic stimulation or inhibition of NO synthase.


Subject(s)
Carbon , Electrophysiology/methods , Membrane Potentials/physiology , Microelectrodes/trends , Neurochemistry/methods , Nitric Oxide/analysis , Nitrites/analysis , 2-Amino-5-phosphonovalerate/pharmacology , Animals , Aorta/drug effects , Aorta/metabolism , Carbon/standards , Carbon Fiber , Electrophysiology/instrumentation , Enzyme Inhibitors/pharmacology , Epinephrine/pharmacology , Excitatory Amino Acid Agonists/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Male , Microelectrodes/standards , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , N-Methylaspartate/pharmacology , NG-Nitroarginine Methyl Ester/pharmacology , Neostriatum/drug effects , Neostriatum/metabolism , Neurochemistry/instrumentation , Rats , Rats, Wistar
15.
Transfusion ; 41(6): 751-5, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11399814

ABSTRACT

BACKGROUND: ALT testing of blood donors was initiated as a surrogate marker for non-A, non-B hepatitis. Increased sensitivity of subsequent HBV and HCV tests used for standard donor screening make any residual value of ALT testing questionable. STUDY DESIGN AND METHODS: A prospective study was conducted in 166 of 645 eligible blood donors from three American Red Cross regions whose ALT was > or =120 IU per L and whose standard donor screening tests were negative. Of these enrolled donors, 124 (75%) completed follow-up. Samples obtained from the index donation, at enrollment (1 month), and at follow-up (6 months) underwent the standard donor screening tests, as well as those for HCV RNA and HGV RNA (RT-PCR), antibodies to the virus envelope E2 protein of GB virus type C (GBV-C E2 antibody), and IgM antibody for CMV, parvovirus B19, EBV VCA, and HAV. Participants completed a brief demographic and exposure history questionnaire at follow-up. RESULTS: All study samples were negative in standard donor-screening tests. ALT levels were variable at return visits, with 80 to 86 percent <120 IU per L. No participants were positive for HCV RNA; 4 percent were positive for HGV RNA, and 10 percent were positive for GBV-C E2 antibody. Results of CMV, parvovirus B19, EBV VCA, and HAV testing were similar to published background rates. No demographic or exposure history variables had significant correlation with ALT or other testing results. CONCLUSION: These data suggest that an ALT > or =120 IU per L in blood donors with negative standard screening tests has questionable value as a surrogate marker for seronegative HBV or HCV infection. Continued ALT testing may contribute little, if anything, to the safety of blood components or plasma for further manufacture.


Subject(s)
Alanine Transaminase/blood , Biomarkers , Blood Donors , Hepatitis, Viral, Human/prevention & control , Adolescent , Adult , Aged , Female , Hepatitis, Viral, Human/blood , Hepatitis, Viral, Human/transmission , Humans , Male , Mass Screening , Middle Aged , Seroepidemiologic Studies , United States
16.
Otolaryngol Head Neck Surg ; 124(4): 421-5, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11283500

ABSTRACT

OBJECTIVES: Microvascular targeting with the 585- nm pulsed dye laser (PDL) may provide a new form of therapy to control symptoms caused by recurrent respiratory papillomatosis (RRP). METHODS: Ten patients with RRP underwent 13 procedures under general anesthesia with the 585-nm PDL. A micromanipulator (11 procedures) and a flexible nasolaryngoscope (2 procedures) were used to deliver the laser pulses. Patients were followed postoperatively according to protocol. RESULTS: Clinical examination revealed regression of papillomas in all patients. Seven patients had complete regression after PDL surgery, and 2 patients had partial response to treatment. One patient was lost to follow-up. No complications were present during this prospective nonrandomized pilot study. CONCLUSION: Patients treated with PDL experienced regression of their papillomas. PDL may provide patients with RRP with an alternative treatment without the risks associated with CO(2) laser surgery. This procedure also has potential to be delivered on an outpatient basis with flexible fiberoptic laryngoscopes.


Subject(s)
Laryngeal Neoplasms/surgery , Laser Therapy/methods , Papilloma/surgery , Vocal Cords/surgery , Adult , Female , Follow-Up Studies , Humans , Laryngeal Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local , Papilloma/pathology , Pilot Projects , Vocal Cords/pathology
17.
J Appl Behav Anal ; 34(4): 511-5, 2001.
Article in English | MEDLINE | ID: mdl-11800192

ABSTRACT

Escape extinction combined with differential reinforcement for acceptance has been demonstrated to be an effective treatment for food selectivity when implemented by trained professionals in clinic settings. This study evaluated the efficacy of parent-implemented escape extinction in the child's natural environment using video monitoring to train parents and assess intervention efficacy. Parents were able to use intervention to significantly increase bites accepted and decrease problem behavior.


Subject(s)
Behavior Therapy/methods , Developmental Disabilities/rehabilitation , Feeding and Eating Disorders/therapy , Food Preferences , Reinforcement, Psychology , Child, Preschool , Developmental Disabilities/psychology , Extinction, Psychological , Feeding and Eating Disorders/psychology , Humans , Male , Self-Injurious Behavior/prevention & control , Self-Injurious Behavior/psychology , Videotape Recording
18.
Eur J Appl Physiol ; 82(5-6): 374-80, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10985590

ABSTRACT

Ten male and ten female young adults trained the knee extensors of one leg eccentrically and those of the other concentrically for 6 weeks, using a gymnasium leg-extension machine. Before and after training, both legs of each subject were tested isometrically for maximum voluntary knee-extensor force, and in both eccentric and concentric isokinetic modes at 30-250 degrees x s(-1) All limbs showed improvements in mean eccentric force (ranging from 18% in the concentrically trained legs of the females to 31% in the eccentrically trained legs of the males, P < 0.01-0.001). Upward trends in isometric and concentric forces were smaller and less- or nonsignificant. In three of the four groups, mean eccentric forces after training were significantly greater than mean isometric forces, a difference that was not evident before training. Ten further subjects of each gender, not trained but tested isometrically and isokinetically three times in 2 weeks, showed no significant improvement over the series of tests. The explanation suggested is that the increased percentage activation ("decreased inhibition"), often regarded as the main mechanism of strength gain in the early weeks of training, had been displayed particularly in the subjects' eccentric performance. This implies that the activation-shortfall, which is reduced by the initial phase of strength training, is largely or completely the same as that responsible for the fact that untrained, voluntary eccentric force is less than that of isolated muscle.


Subject(s)
Muscle, Skeletal/physiology , Physical Fitness/physiology , Adult , Female , Humans , Isometric Contraction/physiology , Leg/physiology , Male , Manometry , Sex Characteristics
19.
Proc Natl Acad Sci U S A ; 97(4): 1506-11, 2000 Feb 15.
Article in English | MEDLINE | ID: mdl-10677491

ABSTRACT

Potent and selective inhibitors of inducible nitric oxide synthase (iNOS) (EC ) were identified in an encoded combinatorial chemical library that blocked human iNOS dimerization, and thereby NO production. In a cell-based iNOS assay (A-172 astrocytoma cells) the inhibitors had low-nanomolar IC(50) values and thus were >1,000-fold more potent than the substrate-based direct iNOS inhibitors 1400W and N-methyl-l-arginine. Biochemical studies confirmed that inhibitors caused accumulation of iNOS monomers in mouse macrophage RAW 264.7 cells. High affinity (K(d) approximately 3 nM) of inhibitors for isolated iNOS monomers was confirmed by using a radioligand binding assay. Inhibitors were >1,000-fold selective for iNOS versus endothelial NOS dimerization in a cell-based assay. The crystal structure of inhibitor bound to the monomeric iNOS oxygenase domain revealed inhibitor-heme coordination and substantial perturbation of the substrate binding site and the dimerization interface, indicating that this small molecule acts by allosterically disrupting protein-protein interactions at the dimer interface. These results provide a mechanism-based approach to highly selective iNOS inhibition. Inhibitors were active in vivo, with ED(50) values of <2 mg/kg in a rat model of endotoxin-induced systemic iNOS induction. Thus, this class of dimerization inhibitors has broad therapeutic potential in iNOS-mediated pathologies.


Subject(s)
Enzyme Inhibitors/chemical synthesis , Nitric Oxide Synthase/antagonists & inhibitors , Allosteric Regulation , Animals , Binding Sites , Cell Line , Combinatorial Chemistry Techniques , Dimerization , Enzyme Inhibitors/pharmacology , Humans , Mice , Models, Molecular , Molecular Structure , Nitric Oxide/blood , Nitric Oxide Synthase Type II , Protein Binding , Rats
20.
Cancer Biother Radiopharm ; 15(6): 645-56, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11190496

ABSTRACT

UNLABELLED: Iotrex is an aqueous radiotherapy solution containing sodium 3-(125I)iodo-4-hydroxybenzenesulfonate (125I-HBS), which is used as the radiation source for the brachytherapy of resected of brain tumor cavity margins with the GliaSite catheter. During routine clinical use of this brachytherapy applicator and radiation source, approximately 0.1% of the afterloaded Iotrex will diffuse through the GliaSite balloon. Our purpose was to assess the radiation doses to normal organs under routine clinical use of the GliaSite. METHODS: Five groups of rats received intracerebral injections of an 131I-HBS solution (131I used as a surrogate for 125I in the synthesis of 125I-HBS) with one group sacrificed at 15 minutes, 30 minutes, 1 hour, 2 hours and 4 hours post-administration. Urine was collected and activity retention in numerous organs was measured. The biodistribution data were used to estimate radiation doses to normal organs of the Reference Adult Male and Female phantoms. RESULTS: Radioactivity was rapidly and completely cleared from the brain (98% cleared by 2 hours) and total body (urinary clearance; 93%@2 hours). No organ retained > 0.7% of the radioactivity at 4 hours. For 100% loss of the radiotherapy solution from the balloon catheter (device failure), all organs would receive less than 100 mGy (10 rad), except the bladder wall (2800 mGy, 280 rad), uterus (130 mGy, 13 rad) and distal colon (270 mGy, 27 rad). Under normal conditions, all organ doses are 1000-fold lower (< 3 mGy or 0.3 rad). CONCLUSIONS: Under routine clinical conditions, the radiation doses to normal organs are inconsequential. Should the maximum clinical load of Iotrex (16.7 GBq of 125I) be released intracerebrally, the radiation doses to all organs would be below the thresholds for deterministic effects.


Subject(s)
Benzenesulfonates/pharmacokinetics , Brachytherapy , Brain Neoplasms/radiotherapy , Brain/metabolism , Animals , Benzenesulfonates/therapeutic use , Brain/radiation effects , Brain Neoplasms/metabolism , Male , Models, Statistical , Radiometry , Rats , Rats, Sprague-Dawley , Tissue Distribution
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