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1.
Nanoscale ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980687

ABSTRACT

The decrease in emission efficiency with increasing drive current density, known as 'droop', of c-plane wurtzite InGaN/GaN quantum wells presently limits the use of light-emitting diodes based on them for high brightness lighting applications. InGaN/GaN quantum wells grown in the alternative zincblende phase are free of the strong polarisation fields that exacerbate droop and so were investigated by excitation-dependent photoluminescence and photoreflectance studies. Polarisation-resolved measurements revealed that for all excitation densities studied the emission from such samples largely originates from similar microstructures or combinations of microstructures that form within the quantum well layers. Emission efficiency varies significantly with excitation at 10 K showing that non-radiative recombination processes are important even at low temperature. The onset of efficiency droop, as determined by photomodulated reflection measurements, occurred at a carrier density of around 1.2 × 1020 cm-3 - an order of magnitude greater than the value reported for a reference wurtzite quantum well sample using the same method. The high carrier density droop onset combined with the much shorter carrier lifetime within zincblende InGaN/GaN quantum wells indicate they have the potential to effectively delay efficiency droop when used in GaN based light-emitting diodes. However, the material quality of the quantum well layers need to be improved by preventing the formation of microstructures within these layers, and the importance of the role played by non-radiative centres in the QW layer needs to be elucidated, to fully realise the material's potential.

2.
Acta Trop ; 205: 105277, 2020 May.
Article in English | MEDLINE | ID: mdl-32035056

ABSTRACT

Dogs can be infected by a wide range of Bartonella spp., but studies regarding the prevalence of Bartonella infection in dogs in the Philippines have not been conducted. This study aimed at determining the prevalence of Bartonella infection in pets dogs from two veterinary clinics in Metro Manila, The Philippines, using both serology and polymerase chain reaction (PCR). Blood samples from 116 dogs from two different groups, one of 60 mainly "healthy dogs" and the other one of 56 dogs enrolled in a tick-borne disease suspect group, were tested for presence of B. henselae antibodies and to detect Bartonella DNA using primers specific for the citrate synthase gene. Seroprevalence for B. henselae was very low (2.6%), as the only three (5%) seropositive dogs (titer 1:64) where among the healthy pet dog group. Following subsequent sequencing, 13 samples, all from the tick-borne disease group, were determined positive for B. henselae (11.2%). This is the first study to report dog infection with B. henselae in the Philippines.


Subject(s)
Bartonella Infections/veterinary , Dog Diseases/epidemiology , Pets/microbiology , Animals , Bartonella Infections/epidemiology , Dogs , Female , Male , Philippines/epidemiology , Prevalence , Seroepidemiologic Studies , Tick-Borne Diseases/epidemiology , Tick-Borne Diseases/veterinary
3.
Am J Trop Med Hyg ; 101(4): 749-752, 2019 10.
Article in English | MEDLINE | ID: mdl-31436150

ABSTRACT

Bartonellae are emerging vector-borne pathogens infecting various domestic and wild mammals. Blood samples were collected from 66 dogs at two locations near Hamedan, Iran. Twenty dogs were rescued stray dogs and 46 dogs were from a breeding colony, with many of them infested with fleas, ticks, or lice. Serology was performed using an indirect immunofluorescent antibody test for Bartonella henselae, Bartonella clarridgeiae, and Bartonella vinsonii subsp. berkhoffii. Seroprevalence was 74.2% (range: 65.2-95%). Bartonella DNA amplification and sequencing identified B. vinsonii subsp. berkhoffii type III in seven dogs, including five rescued dogs. Two dogs were infected with Bartonella rochalimae and three dogs with Candidatus B. merieuxii, including two of the stray dogs coinfected with Bartonella vinsonii subsp. berkhoffii. Rescued stray dogs were 10 times (odds ratio (OR) = 10.13, 95% CI: 1.24-82.7; P = 0.03) more likely to be seropositive and eight times (OR = 8.82, 95% CI: 2.68-29.11; P = 0.0004) more likely to be flea-infested than breeding dogs, confirming that arthropod infestation is a major risk factor for these infections.


Subject(s)
Antibodies, Bacterial/blood , Bartonella Infections/veterinary , Bartonella/immunology , Dog Diseases/epidemiology , Animals , Bartonella/genetics , Bartonella/isolation & purification , Bartonella Infections/epidemiology , Bartonella Infections/microbiology , Dog Diseases/microbiology , Dogs , Female , Fluorescent Antibody Technique, Indirect/veterinary , Iran/epidemiology , Male , Phylogeny , Prevalence , Sentinel Surveillance , Seroepidemiologic Studies , Zoonoses
5.
Opt Express ; 25(16): 19179-19184, 2017 Aug 07.
Article in English | MEDLINE | ID: mdl-29041111

ABSTRACT

Red-, orange-, and green-emitting integrated optoelectronic sources are demonstrated by transfer printing blue InGaN µLEDs onto ultra-thin glass platforms functionally enhanced with II-VI colloidal quantum dots (CQDs). The forward optical power conversion efficiency of these heterogeneously integrated devices is, respectively, 9%, 15%, and 14% for a blue light absorption over 95%. The sources are demonstrated in an orthogonal frequency division multiplexed (OFDM) visible light communication link reaching respective data transmission rates of 46 Mbps, 44 Mbps and 61 Mbps.

6.
J R Coll Physicians Edinb ; 46(3): 163-165, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27959350

ABSTRACT

A 69-year-old female with seropositive rheumatoid arthritis presented with progressive cognitive decline following treatment with infliximab and methotrexate. Cranial MRI showed non-enhancing white matter signal abnormality consistent with demyelination was seen in the antero-inferior left frontal lobe extending into the frontal opercular white matter and into the left temporal lobe white matter. Similar appearances were seen in the inferomedial right frontal lobe. Brain biopsy showed histological changes consistent with progressive multifocal leukoencephalopathy. The cerebrospinal fluid polymerase chain reaction was negative but brain tissue polymerase chain reaction was positive for JC virus. This case highlights the association of infliximab with progressive multifocal leukoencephalopathy in a patient with known seropositive rheumatoid arthritis.


Subject(s)
Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Brain/drug effects , Immunosuppression Therapy/adverse effects , Infliximab/adverse effects , JC Virus , Leukoencephalopathy, Progressive Multifocal/chemically induced , Aged , Antirheumatic Agents/therapeutic use , Brain/pathology , Female , Humans , Infliximab/therapeutic use , Leukoencephalopathy, Progressive Multifocal/cerebrospinal fluid , Leukoencephalopathy, Progressive Multifocal/pathology , Leukoencephalopathy, Progressive Multifocal/virology , Tumor Necrosis Factor-alpha/antagonists & inhibitors
7.
Opt Express ; 23(7): 9329-38, 2015 Apr 06.
Article in English | MEDLINE | ID: mdl-25968763

ABSTRACT

We report the transfer printing of blue-emitting micron-scale light-emitting diodes (micro-LEDs) onto fused silica and diamond substrates without the use of intermediary adhesion layers. A consistent Van der Waals bond was achieved via liquid capillary action, despite curvature of the LED membranes following release from their native silicon growth substrates. The excellence of diamond as a heat-spreader allowed the printed membrane LEDs to achieve optical power output density of 10 W/cm(2) when operated at a current density of 254 A/cm(2). This high-current-density operation enabled optical data transmission from the LEDs at 400 Mbit/s.

8.
Rep Prog Phys ; 76(10): 106501, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24088511

ABSTRACT

The use of III-nitride-based light-emitting diodes (LEDs) is now widespread in applications such as indicator lamps, display panels, backlighting for liquid-crystal display TVs and computer screens, traffic lights, etc. To meet the huge market demand and lower the manufacturing cost, the LED industry is moving fast from 2 inch to 4 inch and recently to 6 inch wafer sizes. Although Al2O3 (sapphire) and SiC remain the dominant substrate materials for the epitaxy of nitride LEDs, the use of large Si substrates attracts great interest because Si wafers are readily available in large diameters at low cost. In addition, such wafers are compatible with existing processing lines for 6 inch and larger wafers commonly used in the electronics industry. During the last decade, much exciting progress has been achieved in improving the performance of GaN-on-Si devices. In this contribution, the status and prospects of III-nitride optoelectronics grown on Si substrates are reviewed. The issues involved in the growth of GaN-based LED structures on Si and possible solutions are outlined, together with a brief introduction to some novel in situ and ex situ monitoring/characterization tools, which are especially useful for the growth of GaN-on-Si structures.


Subject(s)
Gallium/chemistry , Lighting/instrumentation , Nanoparticles/chemistry , Nanotechnology/instrumentation , Optical Devices , Semiconductors , Silicon/chemistry , Crystallization/methods , Equipment Design , Equipment Failure Analysis , Nanoparticles/ultrastructure
9.
Osteoporos Int ; 23(2): 643-54, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21455762

ABSTRACT

SUMMARY: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. INTRODUCTION: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. METHODS: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. RESULTS: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). CONCLUSION: Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.


Subject(s)
Bone Density/physiology , Hyperostosis/physiopathology , Absorptiometry, Photon/methods , Adolescent , Adult , Aged , Aged, 80 and over , Anthropometry/methods , Body Mass Index , Bone Diseases, Developmental/epidemiology , Bone Diseases, Developmental/genetics , Bone Diseases, Developmental/pathology , Bone Diseases, Developmental/physiopathology , Databases, Factual , England/epidemiology , Female , Hip Joint/physiopathology , Humans , Hyperostosis/epidemiology , Hyperostosis/genetics , Hyperostosis/pathology , Lumbar Vertebrae/physiopathology , Male , Mandible/pathology , Middle Aged , Prevalence , Swimming , Wales/epidemiology , Young Adult
10.
Mol Psychiatry ; 15(11): 1053-66, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20157310

ABSTRACT

Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started with a linkage study based on large multigenerational families in a population isolate, followed by fine mapping of targeted regions using a family-based design. Family- and population-based association studies in five samples from disparate regions of the world were used for replication. Brain imaging studies were performed to evaluate gene function. The linkage study discovered a genome region harbored in the Latrophilin 3 gene (LPHN3). In the world-wide samples (total n=6360, with 2627 ADHD cases and 2531 controls) statistical association of LPHN3 and ADHD was confirmed. Functional studies revealed that LPHN3 variants are expressed in key brain regions related to attention and activity, affect metabolism in neural circuits implicated in ADHD, and are associated with response to stimulant medication. Linkage and replicated association of ADHD with a novel non-candidate gene (LPHN3) provide new insights into the genetics, neurobiology, and treatment of ADHD.


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/genetics , Central Nervous System Stimulants/therapeutic use , Genetic Predisposition to Disease , Receptors, G-Protein-Coupled/genetics , Receptors, Peptide/genetics , Adolescent , Adult , Brain/metabolism , Cell Survival/genetics , Child , Child, Preschool , Chromosome Mapping , Female , Genetic Linkage , Genotype , Humans , Magnetic Resonance Spectroscopy/methods , Male , Polymorphism, Genetic , Receptors, G-Protein-Coupled/metabolism , Receptors, Peptide/metabolism
12.
Appetite ; 52(2): 355-62, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19071171

ABSTRACT

Two studies investigated the stress-eating relationship. The first examined self-reported changes in intake of snack foods, whilst the second investigated stress-induced overconsumption in a laboratory setting comparing high (HF) and low-fat (LF) snacks. Eighty-nine females completed the Dutch Eating Behaviour Questionnaire (DEBQ) [Van Strien, T., Fritjers, J. E. R., Bergers, G. P. A., & Defares, P. B. (1986). Dutch Eating Behaviour Questionnaire for assessment of restrained, emotional and external eating behaviour. International Journal of Eating Disorders, 5, 295-315] and a self-report measure designed to evaluate changes in eating in response to stress. Increased intake of HF snacks was associated with high emotional eating but not with restraint. A laboratory-based experiment compared intake of HF and LF snacks after ego-threatening and neutral Stroop colour-naming tasks. Intake was suppressed by 31.8% in restrained compared to unrestrained eaters across tasks. Restrained eaters consumed significantly less after ego-threat than after the neutral manipulation, but this was associated only with intake of the LF snack. Restrained eaters' intake of dried fruit was suppressed by 33.2% after ego-threat relative to the neutral task, despite a significant increase in hunger for this group following ego-threat. These results suggest that the type and variety of foods offered influences the link between stress and eating in laboratory settings. Further research should aim to replicate and extend these findings, with a view to informing potential interventions for stress-related eating.


Subject(s)
Dietary Fats , Emotions , Energy Intake , Feeding Behavior , Stress, Psychological , Adolescent , Body Mass Index , Bulimia , Cacao , Diet, Fat-Restricted , Dietary Carbohydrates , Female , Humans , Internal-External Control , Surveys and Questionnaires , Young Adult
13.
Int J Obes (Lond) ; 29(10): 1199-203, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16155587

ABSTRACT

OBJECTIVE: To assess prevalence and socioeconomic context of overweight and obesity in a cohort of Scottish children. DESIGN: Cross-sectional study. SETTING: Primary schools in Dundee, Angus, and Fife, Eastern Scotland, UK. PARTICIPANTS: A total of 1240 boys and 1214 girls aged between 4-10 y. MAIN OUTCOME MEASURE: Weight, height and body mass index (weight/height2). RESULTS: Overall overweight or obesity prevalence was 24.6%, while prevalence of obesity alone was 6.1%. Individuals from schools with a high level of low-income families were 65% more likely to be overweight as judged by BMI. However, these children weighed the same as more affluent children of the same age, but were 1.26 cm shorter. CONCLUSION: These data confirm the continued increase in childhood obesity in the UK and reveal a role for height-growth limitation in the absence of overall growth restriction, among children from low-income groups. This observation raises important questions regarding socioeconomic environmental factors in promoting the currently increasing levels of obesity.


Subject(s)
Body Height , Obesity/epidemiology , Social Class , Body Mass Index , Child , Child, Preschool , Cohort Studies , Cross-Sectional Studies , Female , Humans , Male , Overweight , Prevalence , Scotland/epidemiology
14.
Appetite ; 43(1): 39-46, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15262016

ABSTRACT

Restrained and emotional eaters overeat in response to stress. To compare differential effects of cognitive demand and ego-threatening stressors on subsequent chocolate intake, 38 females completed a neutral (control), an ego threatening and an incongruent Stroop colour-naming task on three separate occasions. Participants were assigned to four groups based on median-split scores on the restrained and emotional eating scales of the Dutch Eating Behaviour Questionnaire-high restraint/high emotional, high restraint/low emotional, low restraint/high emotional and low restraint/low emotional. Higher response latencies were observed in the incongruent task, confirming its greater cognitive (attentional) demand. Overall intake was enhanced by 23% after ego-threat and 15% after the incongruent Stroop task relative to control. Restraint was associated with greater intake after both ego-threat and the incongruent task than in the control condition. In contrast, emotional eating was associated with greater intake after only the ego-threat, relative to control. A positive association between reaction time and subsequent intake in all conditions for high restraint/low emotional eaters provided support for the limited capacity hypothesis. Enhanced intake in emotional eaters is proposed to relate to escape from self-awareness. These findings demonstrate differential effects of threat and demand on stress-related eating in restrained and emotional eaters.


Subject(s)
Eating/psychology , Feeding Behavior/psychology , Internal-External Control , Stress, Psychological/physiopathology , Stress, Psychological/psychology , Adult , Analysis of Variance , Appetite/physiology , Eating/physiology , Ego , Feeding Behavior/physiology , Female , Humans , Interpersonal Relations , Netherlands , Surveys and Questionnaires
16.
Emerg Med J ; 18(6): 460-1, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11696496

ABSTRACT

OBJECTIVE: To investigate the contribution of alcohol ingestion to the radiological workload of an inner city accident and emergency (A&E) department. METHODS: A prospective survey of patients presenting to A&E who required radiographs was performed over a seven day period. The A&E clinician questioned patients about alcohol intake during the six hours before the onset of the presenting complaint or injury, and made an objective assessment of signs of alcohol ingestion or intoxication. An assessment was made also of the relative contribution of alcohol as a cause of patients' injuries. RESULTS: A total of 419 patients who had radiography fulfilled the inclusion criteria, and a questionnaire was completed for 351 (84%). Forty (11%) of 351 were found to have ingested alcohol. Thirty five (87%) of 40 patients who had ingested alcohol were radiographed for trauma, as compared with 171 (55%) of the 311 who had not (p<0.001). Alcohol was considered to have been causative of injury in 30% and a contributory factor in an additional 58%. Radiographs of the skull, face and jaw accounted for 18 (33%) of 55 radiographs from trauma patients who had ingested alcohol compared with 20 (9%) of 212 radiographs from those who had not (p<0.001). There was no significant difference in the proportion of abnormal radiographs between these two groups (27% of radiographs from trauma patients who had ingested alcohol compared with 23% of radiographs from those who had not, p>0.2). CONCLUSION: Patients with alcohol related injuries requiring radiography have a significant impact on the radiological workload of an A&E department, although the prevalence of alcohol ingestion detected in this study was less than expected from previous studies.


Subject(s)
Alcohol Drinking , Alcoholic Intoxication/complications , Radiology Department, Hospital/statistics & numerical data , Workload/statistics & numerical data , Wounds and Injuries/diagnostic imaging , Adult , Alcohol Drinking/epidemiology , Alcoholic Intoxication/epidemiology , Emergency Service, Hospital , Humans , London/epidemiology , Poverty Areas , Prospective Studies , Radiography , Surveys and Questionnaires , Wounds and Injuries/etiology
17.
Physiol Behav ; 74(3): 283-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11714490

ABSTRACT

To investigate the effects of alcohol on appetite and food intake, 26 males attended the laboratory on three occasions. On each occasion, they were given a standard breakfast. Visual analog scale ratings of hunger, desire to eat and fullness (appetite ratings) were recorded from before breakfast until their return to the laboratory for lunch. Thirty minutes before lunch, subjects either rested (baseline), were given 330 ml of a no-alcohol lager (264 kJ: no-alcohol condition) or 330 ml of the same lager spiked with 3 units of alcohol (24 g ethyl alcohol; total energy=969 kJ: alcohol condition). Ratings of appetite were taken before and after the preload or baseline rest period and again before and hourly after lunch. The test meal at lunch consisted of a buffet-style array of foods and chilled water. Ad libitum intake at lunch (excluding energy from alcohol) was significantly higher following alcohol (7301+/-442 kJ) compared to both baseline (6365+/-334 kJ) and the no-alcohol conditions (6479+/-289 kJ). Appetite ratings failed to demonstrate any differences between alcohol and the no-alcohol condition. Total energy intake (including energy from alcohol) was enhanced in the alcohol condition by 30%, suggesting that energy from alcohol is not compensated in the short-term and may even have a stimulatory effect on food intake.


Subject(s)
Alcohol Drinking/psychology , Appetite/drug effects , Eating/drug effects , Adult , Alcohol Drinking/adverse effects , Energy Intake/drug effects , Humans , Hunger/drug effects , Male , Pain Measurement , Satiety Response/drug effects , Stimulation, Chemical
18.
Arthritis Rheum ; 44(8): 1855-64, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11508439

ABSTRACT

OBJECTIVE: To determine if there are abnormalities in fibrillin 1-containing microfibrils in the extracellular matrix (ECM) of primary dermal fibroblasts explanted from patients with systemic sclerosis (SSc). METHODS: Explanted fibroblasts from unaffected skin of 12 SSc patients were used to examine fibrillin 1-containing microfibrils by immunofluorescence (IF) using a monoclonal antibody (mAb) to fibrillin 1. Metabolic labeling of the fibroblast cultures was used to study the synthesis, secretion, and processing of fibrillin 1, as well as to observe microfibril formation and stability. Microfibrils elaborated by the SSc cells were analyzed by electron microscopy for ultrastructural abnormalities, and the results were confirmed by immunoblotting. RESULTS: Control and SSc fibroblasts displayed a prominent meshwork of fibrillin 1-containing microfibrils when visualized by IF using a fibrillin 1 mAb. Paradoxically, metabolic studies indicated a paucity of fibrillin 1 in the ECM in the majority of the SSc fibroblast strains. Subsequent rotary-shadowed electron microscopy revealed reduced amounts of and ultrastructural abnormalities in the microfibrils elaborated by all strains of SSc cells. Immunoblots confirmed the lack of the high molecular weight form of fibrillin 1 in the SSc fibroblasts of Choctaw American Indians. Finally, in vitro studies indicated that the amount of fibrillin 1 in the ECM of SSc cells diminished at a faster rate than the amount of fibrillin 1 in the ECM of control cells with time. CONCLUSION: Although SSc fibroblasts assemble microfibrils, these microfibrils are unstable, suggesting that an inherent defect of fibrillin 1-containing microfibrils may play a role in the pathogenesis of SSc.


Subject(s)
Dermis/cytology , Fibroblasts/ultrastructure , Microfibrils/ultrastructure , Microfilament Proteins/metabolism , Scleroderma, Systemic/pathology , Adult , Aged , Antibodies, Monoclonal/immunology , Cells, Cultured , Extracellular Matrix Proteins/immunology , Extracellular Matrix Proteins/metabolism , Female , Fibrillin-1 , Fibrillins , Fibroblasts/metabolism , Fluorescent Antibody Technique , Humans , Kinetics , Male , Microfibrils/metabolism , Microfilament Proteins/immunology , Middle Aged , Scleroderma, Systemic/etiology , Scleroderma, Systemic/metabolism
19.
Circulation ; 103(14): 1838-43, 2001 Apr 10.
Article in English | MEDLINE | ID: mdl-11294800

ABSTRACT

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome caused by heparin. Complications range from thrombocytopenia to thrombocytopenia with thrombosis. We report a prospective, historical- controlled study evaluating the efficacy and safety of argatroban, a direct thrombin inhibitor, as anticoagulant therapy in patients with HIT or HIT with thrombosis syndrome (HITTS). METHODS AND RESULTS: Patients with HIT (isolated thrombocytopenia, n=160) or HITTS (n=144) received 2 microgram. kg(-1). min(-1) IV argatroban, adjusted to maintain the activated partial thromboplastin time 1.5 to 3.0 times baseline value. Treatment was maintained for 6 days, on average. Clinical outcomes over 37 days were compared with those of 193 historical control subjects with HIT (n=147) or HITTS (n=46). The incidence of the primary efficacy end point, a composite of all-cause death, all-cause amputation, or new thrombosis, was reduced significantly in argatroban-treated patients versus control subjects with HIT (25.6% versus 38.8%, P=0.014). In HITTS, the composite incidence in argatroban-treated patients was 43.8% versus 56.5% in control subjects (P=0.13). Significant between-group differences by time-to-event analysis of the composite end point favored argatroban treatment in HIT (P=0.010) and HITTS (P=0.014). Argatroban therapy, relative to control subjects, also significantly reduced new thrombosis and death caused by thrombosis (P<0.05). Argatroban-treated patients achieved therapeutic activated partial thromboplastin times generally within 4 to 5 hours of starting therapy and, compared with control subjects, had a significantly more rapid rise in platelet counts (P=0.0001). Bleeding events were similar between groups. CONCLUSIONS: Argatroban anticoagulation, compared with historical control subjects, improves clinical outcomes in patients who have heparin-induced thrombocytopenia, without increasing bleeding risk.


Subject(s)
Anticoagulants/therapeutic use , Heparin/adverse effects , Pipecolic Acids/therapeutic use , Thrombocytopenia/drug therapy , Aged , Anticoagulants/adverse effects , Arginine/analogs & derivatives , Blood Coagulation/drug effects , Blood Coagulation Tests , Diarrhea/chemically induced , Exanthema/chemically induced , Female , Hemorrhage/chemically induced , Humans , Male , Middle Aged , Pain/chemically induced , Pipecolic Acids/adverse effects , Purpura/chemically induced , Sulfonamides , Thrombocytopenia/chemically induced , Treatment Outcome
20.
Hum Mutat ; 16(2): 99-108, 2000.
Article in English | MEDLINE | ID: mdl-10923031

ABSTRACT

Holoprosencephaly (HPE) is the most common developmental defect of the forebrain and midface in humans. In holoprosencephaly the cerebral hemispheres of the brain fail to separate into distinct left and right hemispheres. This malformation is due to the improper specification and formation of the forebrain during early development. When one considers the great number and kinds of genetic interactions that must occur to properly pattern the developing forebrain, it is not surprising that HPE is extremely heterogeneous. In addition to teratogenic agents, several genes are implicated as the cause of HPE. At least 12 different loci have been associated with HPE and now several distinct human genes for holoprosencephaly have been identified. These genes include Sonic Hedgehog (SHH), ZIC2, SIX3, and TG-interacting factor (TGIF). Here we present an overview of the presently known genes causing human holoprosencephaly. We discuss their functional role in development of the forebrain and summarize the mutations and polymorphisms that have been identified within them. Hum Mutat 16:99-108, 2000. Published 2000 Wiley-Liss, Inc.


Subject(s)
Holoprosencephaly/genetics , Mutation/genetics , Animals , Frameshift Mutation/genetics , Humans , Mutation, Missense/genetics , Sequence Deletion
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