The Theileria annulata sporozoite and macroschizont polypeptide encoded by the spm1 gene shares phenylalanine-glycine motifs with nuclear pore proteins.
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Amino Acid Sequence↗
Biomedical subjects
S Williamson
Publications and source records attributed to S Williamson.
Do acute mucosal reactions lead to consequential late reactions in patients with head and neck cancer?
BACKGROUND AND PURPOSE: The relationship between acute and late mucosal reactions remains ill defined but is of considerable relevance to efforts to produce therapeutic gains through the use of altered fractionation schemes and concurrent chemotherapy. We therefore investigated whether acute mucosal reactions in patients treated with an accelerated and a conventionally fractionated radiotherapy regime predicted the severity of late mucosal reactions. PATIENTS AND METHODS: The study population consisted of 191 patients randomised on a prospective trial comparing conventional fractionation at 2 Gy/fraction per day, 70 Gy over 47 days with an accelerated regimen of 59.4 Gy, 1.8 Gy b.i.d over 24 days for Stage III-IV carcinoma of the head and neck. Acute and late mucosal reactions were scored according to RTOG/EORTC criteria and analyzed using multiple regression techniques. RESULTS: The duration of time spent by patients at the acute confluent mucositis grade 3 level was inversely related to the time to onset of the reaction for both fractionation schedules. Time to onset was more rapid for patients treated on the accelerated schedule but time spent at the reaction grade did not differ significantly between the schedules. After correction for treatment and patient related factors, anatomical site (oral cavity/oropharynx versus hypopharynx/larynx) and increasing duration of confluent mucositis emerged as independent predictors of the hazard of late mucosal reactions with the latter effect being more pronounced in the accelerated treatment arm. The expected reduction in late mucosal effects in the accelerated fractionation arm, predicted by the LQ model for late effects was identified only in patients whose acute confluent mucosal reactions lasted less than 20 days. CONCLUSIONS: The presence of individual patient susceptibility factors that determine the severity of acute mucosal reactions is suggested. A link between severe and prolonged acute reactions and the risk of developing late mucosal reactions that is independent of biological dose, has also been found. Purpose designed prospective studies of these issues are necessary.
Acute Disease↗
Self-reported overdose among injecting drug users in London: extent and nature of the problem.
AIMS: To estimate the extent and nature of overdose and factors associated with overdose among injecting drug users in London. DESIGN: Three hundred and twelve current injecting drug users were recruited and interviewed in community settings by a team of "privileged access interviewers". MEASUREMENTS: A structured questionnaire was used that covered the following areas: demographic characteristics, drug use, injecting behaviour, sharing practices, severity of drug dependence, experience of overdose, injecting-related health problems and treatment history. FINDINGS: The results showed that experience of overdose was common (38%). A majority (54%) had witnessed someone else overdose. Overdosing was not a solitary experience; over 80% of subjects who had overdosed had done so in the presence of someone else, but only 27% reported ambulances having been called. Factors found to be associated with overdose were: age at which injecting began; gender (women being more likely to experience overdose); use of alcohol; and polydrug injection. The overall rate of overdosing was one per 6 years of injecting; however, once an individual had an overdose the chance of having another increased. The risk of experiencing a first overdose fell with years of injecting. CONCLUSIONS: Harm-reduction interventions with drug injectors should educate users on the risk factors associated with overdose and actions that should be taken when someone has overdosed. Interventions designed to reduce the risk of overdose may be more effective if they are differentially targeted on drug injectors who have already experienced an overdose.
Adolescent↗
Evaluation of recombinant sporozoite antigen SPAG-1 as a vaccine candidate against Theileria annulata by the use of different delivery systems.
The major sporozoite surface antigen of Theileria annulata (SPAG-1) is a candidate for inclusion in a subunit vaccine. In this paper we summarize the results of 4 vaccination experiments using recombinant SPAG-1 expressed in different systems and presented in different adjuvants. The antigen has been presented as either a C terminal 108 amino acid peptide (called SR1) expressed as both beta-galactosidase and hepatitis B core antigen fusions or as a full-length form expressed as a GST fusion with an N terminal His6 tag. We used different adjuvants, namely Freund's, saponin, ISCOMs and a proprietary adjuvant supplied by SmithKline Beecham, which we call SKBA. The data point to the conclusion that SPAG-1 can elicit partial protection and is therefore suitable for inclusion in an eventual multicomponent subunit vaccine.
Animals↗
Acute toxicity and cost analysis of a phase III randomized trial of accelerated and conventional radiotherapy for squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncology Group study.
The primary purpose of the present analysis was to assess the feasibility and acute toxicity of a pure accelerated fractionation regimen in a cooperative group setting. This analysis included the first 320 patients entered on to the Trans-Tasman Radiation Oncology Group (TROG) randomized controlled trial which compared accelerated radiotherapy (ART) with conventional radiotherapy (CRT) in stage III and IV squamous cell carcinoma (SCC) of the head and neck. Patients were randomized to either 59.4 Gy in 33 fractions over 24 days (ART) or to 70 Gy 35 fractions over 49 days (CRT) after being stratified for site and stage. Accrual began in 1991 and the trial was closed on 3 April 1998 with the targeted 350 patients. The 3-year survival for the whole group was 54%, and the 3-year disease-free survival was 41%. Toxicity data were available on 303 patients (148 ART; 155 CRT). Mucosal toxicity was worse in the accelerated arm, and it peaked approximately 3 weeks earlier than the conventional arm. Skin toxicity was equivalent but occurred approximately 7 days earlier in the accelerated arm. Acute effects in both arms healed completely. Hospitalization was more common in the ART arm (71 vs 52 patients; P = 0.01) but the total bed days in hospital was not greatly different (1707 bed days for ART and 1607 bed days for CRT). Patients were more likely to require nasogastric (NG) feeding in the ART arm (49 vs 33 patients; P = 0.02). There were 1157 NG feeding days for ART and 1154 NG feeding days for CRT. The average cost of radiation treatment per patient including hospitalization, NG feeding and accommodation was $11,750 in the ART arm and $11,587 in the CRT arm. The accelerated arm has been shown to be a tolerable, practical and cost-equivalent regimen. The assessment of the therapeutic ratio of this accelerated protocol (ART) will be determined when the analysis of late effects and loco-regional control is made when the data are more mature.
Adult↗
Clinical correlates of ADHD in females: findings from a large group of girls ascertained from pediatric and psychiatric referral sources.
OBJECTIVE: The scientific literature about attention-deficit hyperactivity disorder (ADHD) is based almost exclusively on male subjects, and girls with ADHD may be underidentified and undertreated. The aim of this study was to examine clinical correlates of ADHD in females using comprehensive assessments in multiple domains of functioning. METHOD: Subjects were 140 girls with ADHD and 122 comparison girls without ADHD ascertained from pediatric and psychiatric referral sources of the same age and social class. Subjects were assessed with structured diagnostic interviews, psychometric tests assessing intellectual functioning and academic achievement, as well as standardized assessments of interpersonal, school, and family functioning by raters who were blind to clinical diagnosis. RESULTS: Compared with female controls, girls with ADHD were more likely to have conduct, mood, and anxiety disorders; lower IQ and achievement scores; and more impairment on measures of social, school, and family functioning. CONCLUSIONS: These results extend to girls previous findings in boys indicating that ADHD is characterized by prototypical core symptoms of the disorder, high levels of comorbid psychopathology, and dysfunction in multiple domains. These results not only support findings documenting phenotypic similarities between the genders but also stress the severity of the disorder in females.
Adolescent↗
Coherent light scattering by nanostructured collagen arrays in the caruncles of the malagasy asities (Eurylaimidae: aves)
We investigated the anatomy, nanostructure and biophysics of the structurally coloured facial caruncles of three species in a clade of birds endemic to Madagascar (Philepittinae, Eurylaimidae: Aves). Caruncle tissues of all species had reflectance spectra with prominent, peak hues between 403 and 528 nm. Dark blue Neodrepanis tissues had substantial reflectance in the near ultraviolet (320-400 nm), which is visible to birds but not to humans, providing the first evidence of ultraviolet skin colours in birds and the first indications of the possible function of ultraviolet skin colours in avian communication. These structural colours are produced by coherent scattering from arrays of parallel collagen fibres in the dermis. Tissues of Philepitta castanea were organized into hexagonal, crystal-like arrays, whereas Neodrepanis tissues were quasiordered. Predictions of the peak hues of reflectance ( &lgr; (max)) using Bragg's law were relatively accurate, but Bragg's law requires physical assumptions that are obviously violated by these structures. A two-dimensional discrete Fourier analysis of the spatial variation in refractive index within the tissues documented that all the tissues are substantially nanostructured at the appropriate spatial scale to scatter visible light coherently. Predicted reflectance spectra based on the two-dimensional Fourier power spectra are relatively accurate at predicting the hue and shape of the reflectance spectra of the tissues. These results confirm that the nanostructure of the collagen arrays determines the colours that are coherently scattered by these tissues. The evolution of the anatomy and nanostructure of asity caruncles is discussed.
Journal Article↗
SPREAD initiative. The Research Team.
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Anemia, Iron-Deficiency↗
As seen on TV: observational study of cardiopulmonary resuscitation in British television medical dramas.
OBJECTIVE: To determine the frequency and accuracy with which cardiopulmonary resuscitation is portrayed in British television medical dramas. DESIGN: Observational study. SUBJECTS: 64 episodes of three major British television medical dramas: Casualty, Cardiac Arrest, and Medics. MAIN OUTCOME MEASURES: Frequency of cardiopulmonary resuscitation shown on television; age, sex, and diagnosis of the patients undergoing resuscitation; rate of survival through resuscitation. RESULTS: Overall 52 patients had a cardiorespiratory arrest on screen and 3 had a respiratory arrest alone, all the arrests occurring in 40 of the 64 episodes. Of the 52 patients having cardiorespiratory arrest, 32 (62%) underwent an attempt at cardiopulmonary resuscitation; 8 attempts were successful. All 3 of the patients having respiratory arrests alone received ventilatory support and survived. On 48% of occasions, victims of cardiac arrest seemed to be less than 35 years old. CONCLUSIONS: Cardiorespiratory resuscitation is often depicted in British television medical dramas. Patients portrayed receiving resuscitation are likely to be in a younger age group than in real life. Though the reasons for resuscitation are more varied and more often associated with trauma than in reality, the overall success rate is nevertheless realistic. Widespread overoptimism of patients for survival after resuscitation cannot necessarily be blamed on British television medical dramas.
Cardiopulmonary Resuscitation↗
Theileria annulata: carrier state and immunity.
Recovery from primary infection of Theileria annulata results in the development of a persistent carrier state in the vertebrate host. The carrier state is of great importance in the maintenance of the life cycle by alternate tick/cattle challenge and both contributes to and may be necessary for maintenance of immunity. Therefore, an accurate determination of carrier animals could be useful in determining immune status and may allow the necessary control measures to be implemented. Detailed information on the carrier state of animals following immunization with attenuated cell lines is lacking. In this study, relationship between immune response, persistence of the parasite, and the antibody response has been investigated. Calves were infected with T. annulata sporozoites, low passage (non-attenuated) or high passage (attenuated, vaccine) cell lines and later challenged with a lethal dose of heterologous sporozoites. The presence and persistence of the parasite were monitored by PCR using primers derived from genes coding for ssrRNA and a 30 kDa major merozoite surface protein, by Giemsa stained blood smears to detect the presence of piroplasms and also by attempting to establish infected mononuclear cell cultures from venous blood. Antibody responses were measured by indirect ELISA using a merozoite recombinant antigen and IFAT using piroplasm and macroschizont antigens. Results showed that there was an evident relationship between the persistence of carrier status, antibody response in ELISA and immune response to challenge.
Animals↗
Acoustic distinctions in the speech of male psychopaths.
A key feature of psychopathy is the ability to deceive, manipulate, and con the unwary, while seeming to be perfectly sincere. Is this impression of sincerity achieved solely through body gestures and facial expression, or is there also something different about the voice quality of psychopaths? We analyzed the acoustic characteristics of speech in 20 male offenders (10 psychopaths and 10 nonpsychopaths), assessed with the Psychopathy Checklist--Revised (Hare, 1991). We used a computer program developed by Alpert, Merewether, Homel, Martz, and Lomask (1986) to measure variations in amplitude and prosody. Results indicated that psychopaths spoke more quietly than controls and did not differentiate, in voice emphasis, between neutral and affective words. These findings are consistent with the developing view that psychopaths are insensitive to the emotional connotations of language. In addition, their vocal characteristics may be part of a self-presentation mode designed to manipulate and control interpersonal interactions.
Adult↗
Diagnostic continuity between child and adolescent ADHD: findings from a longitudinal clinical sample.
OBJECTIVE: To determine whether there are differences in the clinical expression and correlates of attention-deficit hyperactivity disorder (ADHD) between children and adolescents. METHOD: Subjects were 6- to 17-year old Caucasian, non-Hispanic boys with and without ADHD. DSM-III-R structured diagnostic interviews, psychometric measures, and blind raters assessed psychiatric diagnoses, intellectual performance, social disability, school failure, and family functioning. RESULTS: Children and adolescents with ADHD had an almost identical pattern of correlates in multiple domains of assessment including psychosocial adversity and comorbidity with conduct, mood, and anxiety disorders. Although the rate of substance abuse differed in comparison between child and adolescent subjects, this was independent of ADHD status. CONCLUSIONS: These findings document the diagnostic continuity of ADHD between childhood and adolescence and support the inclusion of adolescent samples in ADHD research protocols.
Adolescent↗
Multicenter study of the incidence of and predictive risk factors for diabetic neuropathic foot ulceration.
OBJECTIVE: To investigate longitudinally prognostic factors for foot ulceration in a large population of diabetic patients with established neuropathy. RESEARCH DESIGN AND METHODS: A double-blind multicenter study of a potential new agent for diabetic neuropathy provided the opportunity for this 1-year investigation since intervention demonstrated no efficacy in the condition. A total of 1,035 patients with NIDDM and IDDM were included. Inclusion criteria were vibration perception threshold (VPT) at the great toe > or = 25 V in at least one foot and < or = 50 V in both feet, normal peripheral circulation, and no previous foot ulceration. VPT and clinical components of the Michigan diabetic polyneuropathy (DPN) score were assessed at baseline and subsequent visits. RESULTS: After 1 year, the incidence of first foot ulcers for the total population was 7.2%. Neuropathy parameters were the same between the treatment and placebo groups at baseline and were unchanged at 1 year; therefore, baseline data were combined for multiple regression analysis. VPT, age, and Michigan DPN scores for muscle strength and reflexes were significant independent predictors for first foot ulceration (P < 0.01). For each 1-U increase in VPT values at baseline, the hazard of the first foot ulcer increased by 5.6%. Similarly, for each 1-U increase in muscle strength and reflex components of the Michigan DPN scores, the hazard of the first foot ulcer increased by 5.0%. CONCLUSIONS: Tests of VPT and Michigan DPN scores for muscle strength and reflexes are useful clinical predictors for foot ulceration in diabetic patients with established neuropathy. The rate of subsequent ulceration in the following year was alarmingly high, however, despite standardized foot care education at baseline and regular follow-up visits.
Adult↗
Deliberate self-harm: developing clinical guidelines.
Nurses in an acute admissions psychiatric ward are using reflective practice to develop clinical guidelines for the management of patients who deliberately self-harm. In this article, they describe the cyclical learning processes and reflective techniques involved.
Clinical Nursing Research↗
Cervical screening. Rate of diagnosis of cytological abnormalities is best end point.
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Biopsy↗
Adverse effects of stimulant drugs in a community sample of drug users.
A sample of drug users (n = 158) were contacted and interviewed in non-clinical community settings about their use of Ecstasy, cocaine powder, and amphetamines and the adverse effects of these drugs. Subjects reported a wide range of adverse effects including anxiety problems, depression, mood swings, feelings of paranoia, and panic attacks. Sleep and appetite disturbances were the most commonly reported problems. About half of all subjects reported depression and paranoid feelings associated with their stimulant use. Many of those reporting problems stated that these were mild. However, for all drugs, a substantial minority of users reported adverse effects which they rated as 'severe'. Between 30 and 55% of the sample reported having had at least one 'severe' adverse effect (30% cocaine, 35% Ecstasy and 55% amphetamine). There were clear differences between the different drugs in the likelihood and reported severity of adverse effects. Amphetamine use was associated with significantly more adverse effects and with more severe adverse effects than Ecstasy or cocaine. Cocaine powder was associated with the least severe adverse effects. A common pattern of drug use involved the use of depressant drugs such as opiates and benzodiazepines in addition to stimulants. The stimulant and depressant users were more likely than the stimulants-only users to use stimulants by injection and more likely to report adverse effects associated with stimulant use. The stimulant and depressant users were also more likely to have been treated for a drug problem. Approximately a quarter of the sample stated that they had stopped using stimulants up to the point of interview as a result of their bad experiences.
Adolescent↗
The circulating concentrations of FSH, LH and prolactin in the oestradiol-implanted ovariectomized ewe treated with caffeine.
Caffeine, a trimethylxanthine alkaloid, is a psycho-active drug that effects a wide range of physiological systems, including the reproductive system. Reports of infants with intra-uterine growth retardation and lowered birth weight as a result of in utero exposure to caffeine, are increasing. The drug is also known to alter steroidogenesis but it is not certain whether this is a direct and/or an indirect effect with the involvement of the central nervous system. Thus, an experiment was designed to determine the effect of acute caffeine administration on the circulating concentrations of gonadotrophins and prolactin in the ovariectomized oestradiol-implanted ewe. A single intravenous dose of caffeine (20 mg kg-1 bodyweight) did not affect circulating gonadotrophin concentrations with the parameters for the pulsatile secretion of luteinizing hormone (LH) and the mean concentration of follicle stimulating hormone (FSH) being similar in both experimental and control groups. Circulating prolactin levels, on the other hand, were significantly (P < 0.01) elevated following intravenous treatment with caffeine. The effect was immediate following caffeine administration with elevated concentrations being maintained over the next 3 h before their return to pre-treatment concentrations. The response was bi-phasic with peaks of prolactin concentrations at 1 and 3 h. The results of this experiment show that acute caffeine exposure does not affect the secretion of gonadotrophins from the anterior pituitary gland. Furthermore, they show that acute administration of caffeine stimulates prolactin secretion via an action that is independent of oestradiol feedback and which we suggest, may involve the ACTH/adrenal axis.
Animals↗
Projections of chemically identified myenteric neurons of the small and large intestine of the mouse.
The projections of different subpopulations of myenteric neurons in the mouse small and large intestine were examined by combining immunohistological techniques with myotomy and myectomy operations. The myotomies were used to examine the polarity of neurons projecting within the myenteric plexus and showed that neurons containing immunoreactivity for nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), calbindin and 5-HT projected anally, while neurons with substance P (SP)-immunoreactivity projected orally, in both the small and large intestine. Neurons containing neuropeptide Y (NPY)- and calretinin-immunoreactivity projected locally. In the large intestine, GABA-immunoreactive neurons projected both orally and anally, with more axons tending to project anally. Myectomy operations revealed that circular muscle motor neurons containing NOS/VIP/ +/-NPY and calretinin neurons projected anally both in the small and large intestine, while SP-immunoreactive circular muscle motor neurons projected orally. In the large intestine, GABA-IR circular muscle motor neurons projected both orally and anally. This study showed that although some neurons, such as the NOS/VP inhibitory motor neurons and interneurons, SP excitatory motor neurons and 5-HT interneurons had similar projections to those in other species, the projections of other chemical classes of neurons in the mouse intestine differed from those reported in other species.
Animals↗