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Biomedical subjects

D O'Shaughnessy

Publications and source records attributed to D O'Shaughnessy.

At least 19 recordsLinked to original sources

Activated recombinant factor VII after cardiopulmonary bypass reduces allogeneic transfusion in complex non-coronary cardiac surgery: randomized double-blind placebo-controlled pilot study.

BACKGROUND: Receiving an allogeneic transfusion may be an independent predictor of mortality for patients undergoing cardiac surgery. Furthermore, these patients utilize 15% of all donated blood in the UK. In our unit, 80% of patients undergoing complex non-coronary cardiac surgery requiring cardiopulmonary bypass (CPB) receive an allogeneic transfusion. Activated recombinant FVII (rFVIIa) may be effective in reducing this need for transfusion. METHODS: Twenty patients undergoing complex cardiac surgery were randomized to receive rFVIIa or placebo after CPB and reversal of heparin. RESULTS: Two patients in the rFVIIa group received 13 units of allogeneic red cells and coagulation products compared with eight patients receiving 105 units of allogeneic red cells and coagulation products in the placebo group (relative risk of any transfusion 0.26; confidence interval 0.07-0.9; P=0.037). The groups did not differ for adverse events. CONCLUSION: Despite major limitations (underpowered study and prone to type I error), we have shown that rFVIIa significantly reduces the need for allogeneic transfusion in complex non-coronary cardiac surgery without causing adverse events.

Aged↗

Reducing allogeneic transfusion in cardiac surgery: a randomized double-blind placebo-controlled trial of antifibrinolytic therapies used in addition to intra-operative cell salvage.

BACKGROUND: The transfusion of allogeneic red blood cells and allogeneic coagulation products is associated with risk to the patient and the depletion of an increasingly scarce resource. This prospective, randomized, double-blind, placebo-controlled trial investigated practices to avoid transfusion in patients undergoing first-time cardiac surgery. METHODS: Patients were randomized to one of three treatment groups: an aprotinin group, a tranexamic acid group, and a control group receiving normal saline. Intra-operative cell salvage was used for all patients. The primary outcomes were the number of patients exposed to allogeneic red blood cells, allogeneic coagulation products or any allogeneic transfusion (allogeneic red blood cells and/or allogeneic coagulation products). RESULTS: Patients were 2.5 times more likely to receive any allogeneic transfusion in the tranexamic group than in the aprotinin group (21 patients out of 60 compared with nine out of 60, respectively). The relative risk of any allogeneic transfusion comparing aprotinin with tranexamic acid was 0.43 (95% confidence interval 0.21-0.86; P=0.019). Patients in the control group were four times more likely to receive any allogeneic transfusion when compared with the aprotinin group (37 patients out of 60 compared with nine out of 60, respectively). The relative risk of any allogeneic transfusion comparing aprotinin with control was 0.24 (95% confidence interval 0.13-0.46; P<0.001). CONCLUSIONS: When used in addition to intra-operative cell salvage, aprotinin is the most efficacious pharmacological therapy for reducing patient exposure to any allogeneic transfusion during first-time cardiac surgery.

Adult↗

Echis time, under-carboxylated prothrombin and vitamin K status in intensive care patients.

Vitamin K deficiency is a known cause of coagulopathy in hospitalized patients, but the extent of the problem has not been well assessed. This noninterventional, prospective observational study of 35 adults was undertaken in the intensive care unit (ICU) and examined the incidence of and the methods for diagnosing vitamin K deficiency. Measurements of prothrombin time, Echis time and plasma concentrations of under-carboxylated prothrombin (proteins induced in vitamin K absence or antagonism, PIVKA-II), vitamin K1 and ferritin were made during the 48 h after admission to the unit and repeated if coagulopathy developed later. Plasma vitamin K1 was low in 15 admissions (43%), in 11 cases of patients with coagulopathy and in four cases without coagulopathy. PIVKA-II was present in 12 cases (34%), of whom four had low vitamin K1 levels. All of the eight patients with raised PIVKA-II but normal vitamin K concentration were hyperferritinaemic. We conclude that low plasma vitamin K levels, suggestive of low tissue stores, are common in intensive care patients with or without coagulopathy. As 34% of patients had a raised PIVKA-II, this suggests that vitamin K stores may be insufficient to maintain full gamma-carboxylation of prothrombin and emphasize the need to anticipate vitamin K deficiency in the ICU setting by appropriate supplementation.

Adolescent↗

The outcome of ambulatory DVT management using a multidisciplinary approach.

Low molecular weight heparins (LMWHs) have been demonstrated to be at least as safe and effective as unfractionated heparin (UFH) in the initial management of deep vein thrombosis (DVT). However, the effectiveness of using LMWH in the ambulatory management of DVT in a 'real-life' setting has yet to be evaluated. This multicentre retrospective study involving 697 patients considers the outcome data of patients under- going ambulatory DVT treatment with tinzaparin (Innohep(R), Leo Pharmaceuticals, Risborough, Buckinghamshire, UK). During the 6 months following presentation, 17 (2.5%) patients had confirmed thromboembolic complications, of which 14 occurred subsequent to the initial LMWH treatment phase ('late'). There were no deaths in this group. Bleeding complications were reported in 23 (3.4%) patients, with 13 of these being classified as 'late'. Of these, two events were considered major resulting in hospitalization and death. Hospitalization for all causes was 6.8% (45 patients) with 32 patients being admitted for thromboembolic or bleeding complications. Overall mortality was 6.7%. These results compare favourably with published clinical trial data. This study demonstrates that ambulatory treatment of proven DVT with LMWH is both safe and effective.

Adolescent↗

Differential cell counts in sputum in respiratory epidemiology: a pilot study.

BACKGROUND: The aim of this pilot study was to determine whether measuring sputum differential cell counts, particularly eosinophils, could be a useful method of validating self-reported symptoms suggesting asthma in epidemiologic studies. MATERIALS AND METHODS: In this cross-sectional study, we selected four groups of adult subjects by reported symptoms and diagnoses from among those previously randomly identified in a population study. Subjects were selected with no respiratory symptoms ever (normal group), or reporting a diagnosis of asthma (asthma group), or reporting recurrent wheezing not diagnosed as asthma (wheeze group), or reporting exposure to industrial irritants, but not asthma or wheezing (exposed group). Current respiratory symptoms, airway responsiveness to methacholine challenge, and sputum cell counts were determined. The study was completed by 107 subjects aged 20 to 44 years. RESULTS: There were no significant differences in FEV(1) percent predicted, total cell count, and sputum eosinophil count among the four groups. Subjects with reported asthma had greater airway responsiveness as reflected in a lower bronchial reactivity (BR) index. There was a weak correlation between BR index and sputum eosinophils. CONCLUSION: In a community setting, induced sputum eosinophil cell counts in subjects reporting asthma or wheezing were most often within the normal range and not sufficiently often abnormal to be useful in validating a diagnosis of asthma in epidemiologic studies.

Adult↗

UK patients with deep-vein thrombosis can be safely treated as out-patients.

Deep-vein thrombosis (DVT) affects approximately 1:1000 people, approximately 750 cases/year in a Health Authority of average size. Prior to 1992, patients presenting with DVT were usually admitted for treatment with unfractionated heparin (UFH) over a 5-day period, but pressures on medical admissions have prompted many hospitals to review conditions which could be managed at home. Three different pilot studies commenced in 1996 at three centres in the UK. After 6 months, the protocols used were integrated into the normal care plan of the hospital. In total, 5191 patients were assessed, of whom 1347 were either venogram or Doppler ultrasound positive. Overall 1138 (82%) were treated as out-patients, 75% presenting during 'working hours'. Only 12 patients were readmitted, one with a clinically significant PE. Success was attributed to three factors: assignment of a key person as the project co-ordinator; referral of patients directly to permanent, dedicated staff, either on the Medical Admissions Unit (MAU) or the Accident and Emergency (A&E) department; and the introduction of dedicated anticoagulation nurses. In the 6-month period following initial therapy, complications were well below those in previously published studies. Most patients with DVT in the UK can be treated safely and effectively without being admitted to hospital.

Ambulatory Care↗

Diagnosing occupational asthma: use of induced sputum.

The diagnosis of occupational asthma (OA) needs to be made with as much objective evidence as possible. If there is airway inflammation, measurement of this should be an asset. The objective of this study was to investigate whether there is an increase in induced sputum and blood eosinophils and eosinophil cationic protein (ECP) in OA after work exposure. Patients were assessed after a 2-4 week period at work and away from work with cell counts and ECP assays performed blind to the clinical data. They were considered to have OA if symptoms were worse at work and there was a fall in forced expiratory volume in one second (FEV1) > or =20% or in the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) of four-fold or more compared with away from work. Patients whose symptoms were worse at work but had a change in FEV1 of <20% and in methacholine PC20 of less than four-fold were considered as controls. Sixteen patients were studied. Ten had OA and six were controls. Patients with OA had a significant increase in median (interquartile range) sputum eosinophils and ECP when at work compared with the periods out of work, 10.0 (17.05) versus 0.8 (1.6)% (p=0.007) and 3,840 (6,076) versus 116 (180) microg x L(-1) (p=0.01). They also had a higher blood eosinophil count, 0.3 (0.5) x 10(9) versus 0.2 (0.1) x 10(9) x L(-1) (p=0.013), and a trend towards higher serum ECP levels, 44.0 (20.0) versus 32.0 (18.5) microg x L(-1) (p=0.07). In conclusion, the proportion of eosinophils and levels of eosinophil cationic protein in sputum are particularly high at work in patients with occupational asthma, suggesting that the measurement of these factors can supplement other physiological outcomes in establishing the diagnosis of occupational asthma.

Adult↗

A comparison of active and simulated chiropractic manipulation as adjunctive treatment for childhood asthma.

BACKGROUND: Chiropractic spinal manipulation has been reported to be of benefit in nonmusculoskeletal conditions, including asthma. METHODS: We conducted a randomized, controlled trial of chiropractic spinal manipulation for children with mild or moderate asthma. After a three-week base-line evaluation period, 91 children who had continuing symptoms of asthma despite usual medical therapy were randomly assigned to receive either active or simulated chiropractic manipulation for four months. None had previously received chiropractic care. Each subject was treated by 1 of 11 participating chiropractors, selected by the family according to location. The primary outcome measure was the change from base line in the peak expiratory flow, measured in the morning, before the use of a bronchodilator, at two and four months. Except for the treating chiropractor and one investigator (who was not involved in assessing outcomes), all participants remained fully blinded to treatment assignment throughout the study. RESULTS: Eighty children (38 in the active-treatment group and 42 in the simulated-treatment group) had outcome data that could be evaluated. There were small increases (7 to 12 liters per minute) in peak expiratory flow in the morning and the evening in both treatment groups, with no significant differences between the groups in the degree of change from base line (morning peak expiratory flow, P=0.49 at two months and P=0.82 at four months). Symptoms of asthma and use of 3-agonists decreased and the quality of life increased in both groups, with no significant differences between the groups. There were no significant changes in spirometric measurements or airway responsiveness. CONCLUSIONS: In children with mild or moderate asthma, the addition of chiropractic spinal manipulation to usual medical care provided no benefit.

Adolescent↗

Thalassaemia in Vanuatu, south-west Pacific: frequency and haematological phenotypes of young children.

The archipelago of Vanuatu situated in the South-West Pacific has a high frequency of alpha + thalassaemia and additionally on some of the islands there is a high frequency of beta thalassaemia. As part of a large cohort study to investigate the clinical effect of thalassaemia on malaria on the islands of Espiritu Santo and Maewo in Vanuatu, the gene frequencies of the thalassaemias were determined and blood counts were performed on a cohort of infants from birth to 3 years. The haematological phenotypes of the different thalassaemic genotypes are compared, providing a detailed description of the clinical manifestations of alpha + thalassaemia during early development. In addition, cross-sectional surveys of the population of the two islands were performed to establish the frequency of thalassaemia and other red cell polymorphisms and their geographical distribution.

Child, Preschool↗

A perceptual study of source coding of Fourier phase and amplitude of the linear predictive coding residual of vowel sounds.

A practical question in a Fourier transform coding of speech signals is to what accuracy their amplitude and phase spectra have to be represented without perceptible distortions. In this paper a concern is with the audibility of quantization noise signals which are produced by quantizing the amplitude and phase spectra of vowel sounds. Experiments show that the detection of the noise targets with maskers of a low fundamental frequency is determined mainly by the sharpest temporal resolution of the auditory system in the high-frequency region. For maskers of a high fundamental frequency the detection is determined mainly by the sharpest spectral resolution in the low-frequency region. Noise targets with global random phase and amplitude are relatively more difficult to detect than those produced by a local randomization. Local random phase noise targets are generally more detectable than those produced by local amplitude randomization. The relative importance of phase and magnitude spectra in the Fourier transform coding is strongly dependent on the fundamental frequency of the vowel sounds and the window size used in the short-time Fourier analysis.

Auditory Perception↗

Mechanisms of skin rashes from fenbufen.

Fenbufen-induced skin rash was investigated by determining the metabolism of the drug to reactive products. At least five lipophilic products (unidentified), the active metabolite of this drug, biphenyl acetic acid (BPAA), and a gamma-hydroxylated derivative (gamma-hydroxy[1,1'-biphenyl]-4-butanoic acid) were identified in keratinocytes in vitro and in skin of rats and guinea pigs in vivo. The gamma-OH derivatives of BPAA and fenbufen were recovered from papain digests of the prior ether-extracted keratinocyte proteins. Fenbufen and its gamma-OH metabolite stimulated the production of interleukin-1 from keratinocytes exposed to UV radiation but BPAA did not. Inflammatory reactions from fenbufen may therefore, arise from production of its metabolites which yield IL-1 upon exposure to UV radiation.

Animals↗

Effect of calcitonin-gene-related peptide on postoperative neurological deficits after subarachnoid haemorrhage.

An infusion of calcitonin-gene-related peptide (CGRP) at progressively increased concentrations was given to 15 patients with neurological deficits after intracranial aneurysm surgery for subarachnoid haemorrhage. In 9 of the patients the deficits, quantified by a modified Glasgow coma scale, improved with no adverse effects; after a placebo infusion only 2 of the 15 patients showed improvement. If CGRP can reverse cerebral ischaemia after early intracranial aneurysm surgery, its use may improve the safety of such early surgery, remove the need for late surgery with its increased risk of death from rebleeding, and reduce overall morbidity and mortality of aneurysmal subarachnoid haemorrhage.

Adult↗

Damage induced by systemic kainic acid in rats is dependent upon seizure activity--a behavioral and morphological study.

Kainic acid (KA) was injected intraperitoneally into rats at a dose (9 mg/kg) which produced status epilepticus in approximately 50% of the animals. Rats were categorized into groups that displayed status epilepticus, partial seizures or no effect in the 4 hr following kainic acid injection. Behavioral and morphological changes were characterized for each group. Rats that were not affected by kainic acid were indistinguishable from a saline-injected control group. When sacrificed 4 hr after treatment, rats displaying partial seizures showed morphological changes similar to, but less severe than, those exhibiting status epilepticus. Additional groups were tested and sacrificed 7 days (d) after treatment. Rats from the limited seizure group showed little behavioral or morphological response, while animals from the status epilepticus group had marked behavioral deficits and severe lesions. The tissue damage and its distribution were similar to lesions observed after seizures induced by other convulsants, and in spontaneously epileptic dogs. These results suggest that the extent of damage resulting from systemic administration of KA is dependent on the extent of seizure activity, which may in turn be related to the influence of kainic acid and other excitatory amino acids on the limbic system.

Animals↗

A multispeaker analysis of durations in read French paragraphs.

Understanding how the durations of acoustic segments vary in natural language can lead to more intelligible synthetic speech, and to improved automatic recognition. Toward this goal, a 111-word French paragraph was read by 29 native speakers from France. Measured durations of acoustic segments were significantly shorter than those in earlier studies of stressed words in French sentences read from a list. Previously recognized trends (short schwa vowels and function words; long unvoiced fricatives, nasalized vowels, and prepausal syllables) are confirmed and quantitative results are given. Vowels were longer preceding voiced fricatives (but not prior to/r/), and were also longer at sentence-internal pauses than at the end of a sentence. Standard deviations of acoustic segment durations (at fixed positions in the paragraph) across speakers averaged less than 25% in most cases. The exceptional, larger deviations occurred primarily in segments adjacent to pauses. Speaking rate variations could account for only one-sixth of the deviations, the rest being attributable to relatively free variation across speakers. A generative model of French durations, suitable for synthesis-by-rule, is presented, and applications to automatic recognition are discussed.

Female↗