Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 49
Filter
1.
Ann Burns Fire Disasters ; 30(4): 256-260, 2017 Dec 31.
Article in English | MEDLINE | ID: mdl-29983676

ABSTRACT

In July 2005, four suicide bombers detonated explosive improvised high explosive devices (IEDs) in three separate underground carriages and a double decker bus in London, resulting in 56 deaths and 775 injured. This study aims to understand the mechanisms and patterns of burn injuries from high explosives, and the related factors that determine mortality. The types and patterns of burn injuries in survivors and fatalities in the confined underground train carriages and the bus were analysed, evaluating injury severity score and the victims' relative position from the detonation point. The data were sourced from collated police witness statements, hospital records, forensic post mortem examinations and forensic examinations at the scene. The detonation of an explosive device in a confined space causes complex injuries to the human body, resulting in blast-related direct thermal and radiant burns. Injury patterns and mortality were related to crowd density, enclosure design, position of the victims and proximity to the device. Suicide bombings using IEDs will result in direct thermal burns and radiant burns currently categorised in the quaternary (miscellaneous) blast injury group. We propose a classification of these burns following an analysis of the London bombing data with respect to burns in both the fatalities and survivors. Distance from the device, crowd density and environment influences these burns.


En juillet 2005, 4 kamikazes faisaient exploser leur engin artisanal dans 3 rames de métro et 1 autobus à impériale de Londres, faisant 56 morts et 775 blessés. Cette étude a pour but d'étudier les mécanismes et la physiopathologie des brûlures liées à une explosion ainsi que d'évaluer les facteurs associés de mortalité. Nous avons analysé le type et la localisation des brûlures, l'ISS selon la position des victimes par rapport à l'épicentre. Les données provenaient des témoignages recueillis par les forces de police, des dossiers médicaux, des autopsies et des analyses de site. Une explosion en milieu clos entraînent des lésions complexes parmi lesquelles des brûlures thermiques directes et par radiation. La topographie des lésions et la mortalité étaient en relation avec la densité humaine, la topographie du volume clos, la position des victimes et leur situation par rapport à l'épicentre. Les brûlures directes et par radiation sont actuellement catégorisées dans les blasts quaternaires. A la suite des attentats londoniens, nous proposons une classification de ces brûlures, influencées par la distance à l'épicentre, la densité humaine et l'environnement.

2.
Injury ; 47(8): 1806-10, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27287739

ABSTRACT

The Afghanistan conflict has resulted in a large number of service personnel sustaining amputations. Whilst obvious differences exist between military and civilian trauma-related amputations both settings result in life changing injuries. Comparisons offer the potential of advancement and protection of the knowledge gained during the last 12 years. This paper compares the military and civilian trauma-related amputee cohorts' demographics, management and rehabilitation outcomes measures. The UK military Joint Theatre Trauma Registry and a civilian major trauma centre database of trauma-related amputees were analysed. 255 military and 24 civilian amputees were identified. A significant difference (p>0.05) was seen in median age (24, range 18-43, vs. 48, range 24-87 years), mean number of amputations per casualty (1.6±SD 0.678 vs. 1±SD 0.0), mean ISS (22±SD 12.8 vs. 14.7±SD 15.7) and gender (99% males vs. 78%). Rehabilitation outcome measures recorded included the Special Interest Group in Amputee Medicine score where the military group demonstrated significantly better scores (91% Grade E+ compared to 19%). Differences in patients underlying physiology and psychology, the military trauma system and a huge sustained investment in rehabilitation are all contributing factors for these differing outcomes. However the authors also believe that the use of a consultant-led MDT and central rehabilitation have benefited the military cohort in the acute rehabilitation stage and is reflected in the good short-term outcomes.


Subject(s)
Amputation, Surgical , Amputees/psychology , Military Medicine , Military Personnel/statistics & numerical data , Trauma Centers , Wounds and Injuries/psychology , Adaptation, Physiological , Adaptation, Psychological , Adolescent , Adult , Afghan Campaign 2001- , Aged , Aged, 80 and over , Amputation, Surgical/economics , Amputation, Surgical/psychology , Amputation, Surgical/rehabilitation , Amputees/rehabilitation , Artificial Limbs , Female , Humans , Long-Term Care/economics , Male , Middle Aged , Military Personnel/psychology , Treatment Outcome , United Kingdom/epidemiology , Young Adult
3.
Eur J Orthop Surg Traumatol ; 26(6): 587-90, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27352865

ABSTRACT

Trigger thumb, or stenosing tenovaginitis, is a relatively uncommon condition affecting the flexor pollicis longus tendon of children. The condition is characterized by the formation of a nodule within the tendon and thickening of the tendon sheath as it passes through the flexor pulley of the thumb at the level of the metacarpo-phalangeal joint. The optimum age for surgical intervention continues to be discussed. The aim of this study is to establish the temporal relationship and surgical variables to determine factors that may contribute to recurrence of the condition. A retrospective analysis of the entire surgical logbook and patient notes of a stand-alone consultant paediatric orthopaedic practice was scrutinized. 94 patients, 107 thumbs, over a 13-year period were operated on for trigger thumb. The recurrence rate was found to be 5.61 %. The average age of patients at primary release who went on to recurrence was 2.8 years, which is significantly younger than those that did not recur (p = 0.044). Sensitivity analysis revealed that the primary procedure at an age of less than 2.5 years confers a higher risk of recurrence. The data presented here advocate surgical release of trigger thumb after 2½ years of age, a senior surgeon as lead operator and a transverse skin incision at the level of the nodule or a more extensive "zig-zag" one to clearly see the structures to be released. We recommend that the surgeon ensures the stenosing pulley and sheath are released in their entirety.


Subject(s)
Orthopedic Procedures , Tendons , Trigger Finger Disorder , Age Factors , Child, Preschool , Female , Humans , Male , Orthopedic Procedures/adverse effects , Orthopedic Procedures/methods , Patient Outcome Assessment , Patient Selection , Recurrence , Retrospective Studies , Risk Assessment , Tendons/pathology , Tendons/physiopathology , Tendons/surgery , Time-to-Treatment , Trigger Finger Disorder/diagnosis , Trigger Finger Disorder/surgery , United Kingdom
4.
Injury ; 47(3): 646-52, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26830126

ABSTRACT

INTRODUCTION: Terrorists have used the explosive device successfully globally, with their effects extending beyond the resulting injuries. Suicide bombings, in particular, are being increasingly deployed due to the devastating effect of a combination of high lethality and target accuracy. The aim of this study was to identify trends and analyse the demographics and casualty figures of terrorist bombings worldwide. METHODS: Analysis of the Global Terrorism Database (GTD) and a PubMed/Embase literature search (keywords "terrorist", and/or "suicide", and/or "bombing") from 1970 to 2014 was performed. RESULTS: 58,095 terrorist explosions worldwide were identified in the GTD. 5.08% were suicide bombings. Incidents per year are increasing (P<0.01). Mean casualty statistics per incidents was 1.14 deaths and 3.45 wounded from non-suicide incidents, and 10.16 and 24.16 from suicide bombings (p<0.05). The kill:wounded ratio was statistically higher in suicide attacks than non-suicide attacks, 1:1.3 and 1:1.24 respectively (p<0.05). The Middle East witnessed the most incidents (26.9%), with Europe (13.2%) ranked 4th. The literature search identified 41 publications reporting 167 incidents of which 3.9% detailed building collapse (BC), 60.8% confined space (CS), 23.5% open space (OS) and 11.8% semi-confined space (SC) attacks. 60.4% reported on suicide terrorist attacks. Overall 32 deaths and 180 injuries per incident were seen, however significantly more deaths occurred in explosions associated with a BC. Comparing OS and CS no difference in the deaths per incident was seen, 14.2(SD±17.828) and 15.63 (SD±10.071) respectively. However OS explosions resulted in significantly more injuries, 192.7 (SD±141.147), compared to CS, 79.20 (SD±59.8). Extremity related wounds were the commonest injuries seen (32%). DISCUSSION/CONCLUSION: Terrorist bombings continue to be a threat and are increasing particularly in the Middle East. Initial reports, generated immediately at the scene by experienced coordination, on the type of detonation (suicide versus non-suicide), the environment of detonation (confined, open, building collapse) and the number of fatalities, and utilising the Kill:Wounded ratios found in this meta-analysis, can be used to predict the number of casualties and their likely injury profile of survivors to guide the immediate response by the medical services and the workload in the coming days.


Subject(s)
Blast Injuries/epidemiology , Bombs/statistics & numerical data , Terrorism/statistics & numerical data , Blast Injuries/prevention & control , Databases, Factual , Europe/epidemiology , Explosions/statistics & numerical data , Homicide/statistics & numerical data , Humans , Middle East/epidemiology , Suicide/statistics & numerical data , United States/epidemiology
5.
J R Army Med Corps ; 162(1): 12-7, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25512441

ABSTRACT

The First World War (1914-1918) was the first truly industrial conflict in human history. Never before had rifle fire and artillery barrage been employed on a global scale. It was a conflict that over 4 years would leave over 750,000 British troops dead with a further 1.6 million injured, the majority with orthopaedic injuries. Against this backdrop, the skills of the orthopaedic surgeon were brought to the fore. Many of those techniques and systems form the foundation of modern orthopaedic trauma management. On the centenary of 'the War to end all Wars', we review the significant advances in wound management, fracture treatment, nerve injury and rehabilitation that were developed during that conflict.


Subject(s)
General Surgery/history , Military Medicine/history , World War I , Femoral Fractures/surgery , History, 20th Century , Humans , Trauma, Nervous System/surgery
6.
Clin Orthop Relat Res ; 473(9): 2848-55, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26028596

ABSTRACT

BACKGROUND: Personal protection equipment, improved early medical care, and rapid extraction of the casualty have resulted in more injured service members who served in Afghanistan surviving after severe military trauma. Many of those who survive the initial trauma are faced with complex wounds such as multiple amputations. Although costs of care can be high, they have not been well quantified before. This is required to budget for the needs of the injured beyond their service in the armed forces. QUESTION/PURPOSES: The purposes of this study were (1) to quantify and describe the extent and nature of traumatic amputations of British service personnel from Afghanistan; and (2) to calculate an estimate of the projected long-term cost of this cohort. METHODS: A four-stage methodology was used: (1) systematic literature search of previous studies of amputee care cost; (2) retrospective analysis of the UK Joint Theatre Trauma and prosthetic database; (3) Markov economic algorithm for healthcare cost and sensitivity analysis of results; and (4) statistical cost comparison between our cohort and the identified literature. RESULTS: From 2003 to 2014, 265 casualties sustained 416 amputations. The average number of limbs lost per casualty was 1.6. The most common type of amputation was a transfemoral amputation (153 patients); the next most common amputation type was unilateral transtibial (143 patients). Using a Markov model of healthcare economics, it is estimated that the total 40-year cost of the UK Afghanistan lower limb amputee cohort is £288 million (USD 444 million); this figure estimates cost of trauma care, rehabilitation, and prosthetic costs. A sensitivity analysis on our model demonstrated a potential ± 6.19% variation in costs. CONCLUSIONS: The conflict in Afghanistan resulted in high numbers of complex injuries. Our findings suggest that a long-term facility to budget for veterans' health care is necessary. CLINICAL RELEVANCE: Estimates here should be taken as the start of a challenge to develop sustained rehabilitation and recovery funding and provision.


Subject(s)
Afghan Campaign 2001- , Amputation, Surgical/economics , Amputation, Surgical/rehabilitation , Amputees/rehabilitation , Health Care Costs , Long-Term Care/economics , Military Medicine/economics , Military Personnel , Wounds and Injuries/economics , Wounds and Injuries/surgery , Algorithms , Artificial Limbs/economics , Databases, Factual , Humans , Markov Chains , Models, Economic , Models, Statistical , Prosthesis Fitting/economics , Retrospective Studies , Time Factors , Treatment Outcome , United Kingdom
7.
Eur J Orthop Surg Traumatol ; 25(6): 1051-5, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25953634

ABSTRACT

Heterotopic ossification (HO) is the formation of bone at extra-skeletal sites. Reported rates of HO after hip arthroplasty range from 8 to 90 %; however, it is only severe cases that cause problems clinically, such as joint stiffness. The effects of surgical-related controllable intra-operative risk factors for the formation of HO were investigated. Data examined included gender, age of patient, fat depth, length of operation, incision length, prosthetic fixation method, the use of pulsed lavage and canal brush, and component size and material. All cases were performed by the same surgeon using the posterior approach. A total of 510 cases of hip arthroplasty were included, with an overall rate of HO of 10.2 %. Longer-lasting operations resulted in higher grades of HO (p = 0.047). Incisions >10 cm resulted in more widespread HO formation (p = 0.021). No further correlations were seen between HO formation and fat depth, blood loss, instrumentation, fixation methods or prosthesis material. The mini-incision approach is comparable to the standard approach in the aetiology of HO formation, and whilst the rate of HO may not be controllable, a posterior mini-incision approach can limit its extent.


Subject(s)
Arthroplasty, Replacement, Hip/adverse effects , Ossification, Heterotopic/etiology , Adult , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip/methods , Blood Loss, Surgical , Female , Hip Prosthesis , Humans , Male , Middle Aged , Operative Time , Ossification, Heterotopic/diagnostic imaging , Prosthesis Design , Radiography , Retrospective Studies , Young Adult
8.
J R Army Med Corps ; 161(4): 345-7, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25645697

ABSTRACT

Heterotopic ossification (HO) is the formation of bone at extraskeletal sites. Over 60% of amputees injured by improvised explosive devices in the recent conflict in Afghanistan have developed HO, resulting in functional impairment. It is hypothesised that a key aetiological factor is the blast wave; however, other environmental and medical risk factors, which the casualties have been exposed to, have also been postulated. The suicide terrorist bombings in London in 2005 resulted in many blast-related casualties, many of whom were managed by the Royal London Hospital. This cohort of severely injured patients whose injuries also included trauma-related amputations shared some, but not all, of the risk factors identified in the military population. We reviewed these patients, in particular to assess the presence or absence of military-established risk factors for the formation of HO in these casualties.


Subject(s)
Amputation, Traumatic/complications , Blast Injuries/complications , Bombs , Mass Casualty Incidents , Ossification, Heterotopic/diagnosis , Ossification, Heterotopic/epidemiology , Adult , Cohort Studies , Explosions , Female , Humans , London , Male , Middle Aged
9.
Bull Environ Contam Toxicol ; 92(4): 404-9, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24458246

ABSTRACT

The purpose of this study was to determine the persistence of 2,4-dichlorophenoxyacetic acid (2,4-D) applied to two lakes (one mesotrophic and one eutrophic) for the control of Eurasian watermilfoil (EWM), and to determine the impacts of 2,4-D on benthic macroinvertebrates in one of the lakes. One lake was treated with a liquid formulation, and the other with a slow release granular formulation of 2,4-D. Concentrations of 2,4-D in the water column were highest 1 and 2 days post-treatment and declined to below detection limits by 7 and 10 days post-treatment. We observed negative correlations between days post-treatment and taxa richness, and between days post-treatment and abundance of three of 12 taxonomic groups of macroinvertebrates. Lake managers need to balance control of EWM with possible impacts of 2,4-D to nontarget organisms.


Subject(s)
2,4-Dichlorophenoxyacetic Acid/toxicity , Herbicides/toxicity , Invertebrates/drug effects , Water Pollutants, Chemical/toxicity , Animals , Ecosystem , Lakes/chemistry , Magnoliopsida , Wisconsin
10.
Epidemiol Infect ; 142(2): 352-7, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23711104

ABSTRACT

A foodborne outbreak with 49 cases (22 culture positive for Campylobacter sp.) following a wedding party in the East of England was investigated. A retrospective cohort study identified an association between consumption of chicken liver pâté and infection with Campylobacter jejuni/coli. There was a statistically significant association between dose (amount of chicken liver pâté eaten) and the risk of disease ['tasted': odds ratio (OR) 1·5, 95% confidence interval (CI) 0·04-∞; 'partly eaten': OR 8·4, 95% CI 1·4-87·5; 'most or all eaten': OR 36·1, 95% CI 3·3-2119). The local authority found evidence that the preparation of chicken livers breached Food Standards Agency's guidelines. This epidemiological investigation established a clear dose-response relationship between consumption of chicken liver pâté and the risk of infection with Campylobacter. The continuing need to raise public awareness of the risk to human health posed by undercooked chicken liver is evident.


Subject(s)
Campylobacter Infections/epidemiology , Disease Outbreaks/statistics & numerical data , Foodborne Diseases/epidemiology , Adult , Animals , Campylobacter , Campylobacter Infections/etiology , Campylobacter Infections/microbiology , Chickens/microbiology , England/epidemiology , Female , Foodborne Diseases/etiology , Gastroenteritis/epidemiology , Gastroenteritis/etiology , Humans , Liver , Male , Meat/adverse effects , Meat/microbiology , Middle Aged
12.
Article in English | MEDLINE | ID: mdl-19965273

ABSTRACT

Active echolocation is a sensory modality possessed by a variety of mammals and is used for the identification, classification and localization of objects. A multi stage model of the bat echolocation process has been used with recordings of rotated disks to plot frequency spectrums of the signals reaching each of the bats' ears. Recordings from objects made within the human audible frequency range have also been made for use in psychoacoustic experiments aimed at validating preliminary studies that have shown some human ability to localize objects using echolocation.


Subject(s)
Chiroptera/physiology , Echolocation/physiology , Animals , Biomedical Engineering , Humans , Models, Biological , Psychoacoustics , Species Specificity
14.
Prev Vet Med ; 87(3-4): 327-39, 2008 Nov 17.
Article in English | MEDLINE | ID: mdl-18639946

ABSTRACT

Feline upper respiratory tract disease (URTD), mainly caused by feline calicivirus (FCV) and feline herpesvirus, is a major cause of disease outbreaks in feline accommodation such as animal shelters, catteries and multi-cat households. We conducted a longitudinal, yearlong study in five UK feline animal shelters to identify risk factors for the time to diagnosis of URTD. We were especially interested in risk factors that could be identified at the time the cat entered the shelter. Shelter staff recorded data for 1,434 cats during 2002-2003. Most of the cats were domestic shorthair cats and were from private households, or were stray or abandoned. Sixty cats without clinical signs of URTD at entry had URTD diagnosed (typically within the first month at the centre). We used two multivariable models: one was a Cox proportional-hazards model, and the other a regression analyses with complementary log-log model. The hazard varied substantially between shelters and was considerably lower for the shelter that had a purpose-built admissions unit with its own isolation facilities. The hazard was greater for purebred cats (HR 4.3-5.0) and for neutered cats (HR 2.0). The hazard was also typically greater if the centre had a greater proportion of cats present with URTD. The analyses suggested that the centre-level risk factors were more important in determining hazard than cat-level risk factors.


Subject(s)
Cat Diseases/diagnosis , Respiratory Tract Infections/veterinary , Animal Welfare/organization & administration , Animals , Cat Diseases/epidemiology , Cats , Housing, Animal , Proportional Hazards Models , Regression Analysis , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Risk , Risk Factors , Time Factors , United Kingdom/epidemiology
15.
Vaccine ; 22(25-26): 3270-3, 2004 Sep 03.
Article in English | MEDLINE | ID: mdl-15308349

ABSTRACT

Following concerns raised over the safety of canine vaccines, an epidemiological investigation was conducted to evaluate the evidence for a temporal association between vaccination and ill-health in dogs. The owners of a randomly selected population of dogs were sent 9055 postal questionnaires, 4040 of which were returned. No temporal association was found between vaccination and ill-health in dogs after adjusting for potential confounders, such as age. However, reliable inferences from non-significant test results are limited and so equivalence-testing methods were also used to make informative inferences. Results demonstrated that recent vaccination (< 3 months) does not increase signs of ill-health by more than 0.5% and may actually decrease it by as much as 5%. This general approach should be used in all field studies of vaccine safety.


Subject(s)
Dog Diseases/epidemiology , Vaccination/adverse effects , Animals , Cross-Sectional Studies , Dogs , Female , Health Status Indicators , Male , Surveys and Questionnaires , Time Factors , United Kingdom/epidemiology
16.
Vet Comp Oncol ; 1(4): 200-6, 2003 Dec.
Article in English | MEDLINE | ID: mdl-19379181

ABSTRACT

Canine lymphoma is one of the commonest forms of spontaneous canine neoplasia. Improved understanding of the genetic and environmental risk factors for canine lymphoma, including breed differences, may have comparative benefits for the study of non-Hodgkin's lymphoma in humans. In this study, data from a pet insurance company were used to estimate the incidences of canine lymphoma for pedigree breeds in the UK. Out of a total of 130,684 insured dogs, 103 had a diagnosis of lymphoma recorded. A significant breed effect was found with the boxer, bulldog and bull mastiff breeds, all having a high incidence of lymphoma. The small number of lymphoma cases recorded may have limited our ability to detect other breeds with an elevated risk. Incidence of lymphoma was found to increase with age, peaking at 10 years of age.

18.
Bioconjug Chem ; 12(4): 554-8, 2001.
Article in English | MEDLINE | ID: mdl-11459460

ABSTRACT

Radiolytic degradation of radiolabeled compounds is a major challenge for the development of new therapeutic radiopharmaceuticals. The goal of this study is to explore the factors influencing the solution stability of a (90)Y-labeled DOTA-peptide conjugate (RP697), including the amount of total activity, the activity concentration, the stabilizer concentration, and the storage temperature. In general, the rate of radiolytic decomposition of RP697 is much slower at the lower activity concentration (<4 mCi/mL) than that at the higher concentration (>10 mCi/mL). RP697 remains relatively stable at the 20 mCi level and room temperature while it decomposes rapidly at the 100 mCi level under the same storage conditions. Radical scavengers, such as gentisic acid (GA) and ascorbic acid (AA), were used in combination with the low temperature (-78 degrees C) to prevent the radiolytic decomposition of RP697. It was found that RP697 remains stable for at least 2 half-lives of (90)Y when GA or AA (10 mg for 20 mCi of (90)Y) is used as a stabilizer when the radiopharmaceutical composition is stored at -78 degrees C. The stabilizer (GA and AA) can be added into the formulation either before or after radiolabeling. The post-labeling approach is particularly useful when the use of a large amount of the stabilizer interferes with the radiolabeling. The radiopharmaceutical composition developed in this study can also apply to other (90)Y-labeled DOTA-biomolecule conjugates. The amount of the stabilizer used in the radiopharmaceutical composition and storage temperature should be adjusted according to the sensitivity of the radiolabeled DOTA-biomolecule conjugate toward radiolytic decomposition.


Subject(s)
Ascorbic Acid/chemistry , Gentisates , Heterocyclic Compounds, 1-Ring/chemistry , Heterocyclic Compounds, 1-Ring/chemical synthesis , Hydroxybenzoates/chemistry , Oligopeptides/chemistry , Peptides, Cyclic/chemistry , Yttrium Radioisotopes/chemistry , Attention/physiology , Dose-Response Relationship, Drug , Drug Stability , Free Radical Scavengers/chemistry , Solutions/chemistry , Temperature
19.
Bioconjug Chem ; 12(4): 559-68, 2001.
Article in English | MEDLINE | ID: mdl-11459461

ABSTRACT

The (90)Y and (177)Lu complexes (RP697 and RP688, respectively) of a DOTA-conjugated vitronectin receptor antagonist (SU015: 2-(1,4,7,10-tetraaza-4,7,10-tris(carboxymethyl)-1-cyclododecyl)acetyl-Glu(cyclo[Lys-Arg-Gly-Asp-D-Phe])-cyclo[Lys-Arg-Gly-Asp-D-Phe]) were prepared by reacting SU015 with the radiometal chloride in ammonium acetate buffer (pH > 7.2) in the presence of an antioxidant (sodium gentisate, GA). Through a series of radiolabeling experiments, it was found that there are many factors influencing the rate of (90)Y chelation and the radiolabeling efficiency of SU015. These include the purity of SU015, the pH, reaction temperature, and heating time, as well as the presence of trace metal contaminants, such as Ca(2+), Fe(3+), and Zn(2+). The chelation of (90)Y by SU015 is slow, so that heating at elevated temperatures (50-100 degrees C) is needed to complete the (90)Y-labeling. The rate of (90)Y chelation is also dependent on the pH of the reaction mixture. Under optimized radiolabeling conditions (pH 7.2-7.8 and heating at 50-100 degrees C for 5-10 min), the minimum amount of SU015 required to achieve 95% RCP for RP697 is approximately 25 microg for 20 mCi of (90)YCl(3) corresponding to a SU015:(90)Y ratio of approximately 30:1.


Subject(s)
Heterocyclic Compounds, 1-Ring/chemistry , Lutetium/chemistry , Oligopeptides/chemical synthesis , Peptides, Cyclic/chemistry , Radioisotopes/chemistry , Yttrium Radioisotopes/chemistry , Chelating Agents/chemistry , Gentisates/chemistry , Heating , Heterocyclic Compounds, 1-Ring/chemical synthesis , Hydrogen-Ion Concentration , Oligopeptides/pharmacology , Peptides, Cyclic/chemical synthesis , Receptors, Vitronectin/antagonists & inhibitors , Temperature
20.
Bioconjug Chem ; 12(4): 624-9, 2001.
Article in English | MEDLINE | ID: mdl-11459468

ABSTRACT

This report describes the (99m)Tc labeling of a HYNIC-conjugated vitronectin receptor antagonist (SQ168 = [2-[[[5-[carboonyl]-2-pyridinyl]hydrazono]methyl]benzenesulfonic acid]-Glu(cyclo[Lys-Arg-Gly-Asp-D-Phe])-cyclo[Lys-Arg-Gly-Asp-D-Phe]). The ternary ligand complex [(99m)Tc(SQ168)(tricine)(TPPTS)] (RP593) was prepared using a non-SnCl(2)-containing formulation. The corresponding (99)Tc analogue, [(99)Tc]RP593, was also prepared and characterized by HPLC and LC-MS. A HPLC concordance experiment using RP593 and [(99)Tc]RP593 showed that the same technetium complex was prepared at both the tracer and macroscopic levels. The LC-MS data is completely consistent with the 1:1:1:1 composition for Tc:SQ168:tricine:TPPTS and provides direct evidence that the two radiometric peaks in the radio-HPLC chromatogram of RP593 are indeed due to the resolution of diastereomers. In an in vitro receptor binding assay, [(99)Tc]RP593 was shown to have comparable binding affinity for the vitronectin receptor to that of SQ168 itself.


Subject(s)
Hydrazines/chemistry , Niacinamide/analogs & derivatives , Niacinamide/chemistry , Organotechnetium Compounds/chemistry , Organotechnetium Compounds/chemical synthesis , Peptides, Cyclic/chemistry , Peptides, Cyclic/chemical synthesis , Peptides/chemistry , Radioisotopes/chemistry , Receptors, Vitronectin/antagonists & inhibitors , Technetium/chemistry , Binding, Competitive/physiology , Chromatography, High Pressure Liquid , Chromatography, Liquid , Drug Stability , Humans , Mass Spectrometry , Neoplasms/diagnostic imaging , Organotechnetium Compounds/metabolism , Peptides/pharmacology , Peptides, Cyclic/metabolism , Placenta/metabolism , Radionuclide Imaging
SELECTION OF CITATIONS
SEARCH DETAIL
...