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Biomedical subjects

S Scott

Publications and source records attributed to S Scott.

At least 19 recordsLinked to original sources

Impact of a theoretically based sex education programme (SHARE) delivered by teachers on NHS registered conceptions and terminations: final results of cluster randomised trial.

OBJECTIVE: To assess the impact of a theoretically based sex education programme (SHARE) delivered by teachers compared with conventional education in terms of conceptions and terminations registered by the NHS. DESIGN: Follow-up of cluster randomised trial 4.5 years after intervention. SETTING: NHS records of women who had attended 25 secondary schools in east Scotland. PARTICIPANTS: 4196 women (99.5% of those eligible). INTERVENTION: SHARE programme (intervention group) v existing sex education (control group). MAIN OUTCOME MEASURE: NHS recorded conceptions and terminations for the achieved sample linked at age 20. RESULTS: In an "intention to treat" analysis there were no significant differences between the groups in registered conceptions per 1000 pupils (300 SHARE v 274 control; difference 26, 95% confidence interval -33 to 86) and terminations per 1000 pupils (127 v 112; difference 15, -13 to 42) between ages 16 and 20. CONCLUSIONS: This specially designed sex education programme did not reduce conceptions or terminations by age 20 compared with conventional provision. The lack of effect was not due to quality of delivery. Enhancing teacher led school sex education beyond conventional provision in eastern Scotland is unlikely to reduce terminations in teenagers. TRIAL REGISTRATION: ISRCTN48719575 [controlled-trials.com].

Abortion, Induced↗

Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development.

Amino Acid Sequence↗

At risk individuals.

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Carcinoma, Squamous Cell↗

Repositioning the patient: the implications of being 'at risk'.

In the modern era of biomedical practice, genetic knowledge has redefined the idea of 'the patient' to include those who are 'at risk' of disease alongside those who are already sick. For such individuals, it is risk itself that constitutes the raison d'être of medical intervention. Using data from interviews with 58 users of a UK cancer genetics service together with data derived from clinical consultations, we consider the way such patients or clients make sense of a cancer genetic risk estimate and how they integrate genetic risk information into their lifeworld. In particular, we note that patient-clients who are 'at risk' tend to see themselves in a liminal position betwixt the healthy and the sick, and that such individuals consequently seek recourse to systems of medical surveillance that can continuously monitor their state of health. Our analysis also revealed the fact that many of those deemed by professionals to be at low risk of inheriting cancer-related mutations subsequently strove to be re-categorised as being at moderate or high risk of an adverse outcome. A number of explanations concerning lay health beliefs, lay 'representations' of health and the nature of the patient-client's lifeworld are examined and assessed in order to account for this apparent paradox.

Attitude to Health↗

Evaluation of a synthetic CArG promoter for nitric oxide synthase gene therapy of cancer.

Nitric oxide synthase gene therapy has been shown to be effective at inducing apoptosis in experimental tumours and sensitizing them to radiotherapy. We have also shown that expression of inducible nitric oxide synthase (iNOS) can be effectively restricted to the tumour volume by the use of the radiation inducible promoter (WAF1) to drive the transgene in clinically relevant protocols. A synthetic construct (pE9), incorporating nine radiosensitive CArG elements from the Egr1 promoter, has recently been developed for cancer gene therapy. We have now investigated basal gene expression of transgenes driven by this promoter to assess its suitability for use in iNOS gene therapy protocols in vivo. Transfection of human microvascular endothelial cells (HMEC-1) with pE9iNOS, using a cationic lipid vector, resulted in progressively increasing (<5-fold) levels of iNOS protein expression up to 8 h after transfection. Transfection of an ex vivo rat artery preparation with pE9iNOS caused 83% inhibition of response to the vasoconstrictor phenylephrine (PE). CMViNOS transfection also reduced response to PE, but by only 52%. A single injection of 25 microg of pE9iNOS DNA in a lipid vector into the centre of a murine sarcoma (RIF1) induced iNOS protein expression by four-fold and increased nitrite concentration eight-fold. This caused a 7-day delay in tumour growth and was more effective than the constitutive CMV-driven construct. Our data suggest that generation of NO*, as a result of iNOS overexpression, is capable of further activating the E9 promoter, through a positive feedback loop, yielding stronger and sustained levels of NO*. This pE9iNOS combination may, therefore, be particularly useful in an anticancer gene therapy strategy as its antitumour effect in vivo was clearly superior to that of the strong constitutive promoter, CMV.

Animals↗

Deafness to fear in boys with psychopathic tendencies.

The processing of the emotional signals of others is fundamental for normal socialization and interaction. Reduced responsiveness to the expressions of sadness and fear has been implicated in the development of psychopathy (Blair, 1995). The current study investigates the ability of boys with psychopathic tendencies to process auditory affect information. Boys with psychopathic tendencies and a comparison group, as defined by the Antisocial Process Screening Device (APSD: Frick & Hare, 2001), were presented with neutral words spoken with intonations conveying happiness, disgust, anger, sadness and fear and were asked to identify the emotion of the speaker based on prosody. The boys with psychopathic tendencies presented with a selective impairment for the recognition of fearful vocal affect. These results are interpreted with reference to amygdala dysfunction and components of the Integrated Emotion Systems model.

Affect↗

Reappraisal of the historical selective pressures for the CCR5-Delta32 mutation.

HIV strains are unable to enter macrophages that carry the CCR5-Delta32 deletion; the average frequency of this allele is 10% in European populations. A mathematical model based on the changing demography of Europe from 1000 to 1800 AD demonstrates how plague epidemics, 1347 to 1670, could have provided the selection pressure that raised the frequency of the mutation to the level seen today. It is suggested that the original single mutation appeared over 2500 years ago and that persistent epidemics of a haemorrhagic fever that struck at the early classical civilisations served to force up the frequency to about 5x10(-5) at the time of the Black Death in 1347.

Disease Outbreaks↗

What caused the Black Death?

For the whole of the 20th century it was believed that the Black Death and all the plagues of Europe (1347-1670) were epidemics of bubonic plague. This review presents evidence that this view is incorrect and that the disease was a viral haemorrhagic fever, characterised by a long incubation period of 32 days, which allowed it to be spread widely even with the limited transport of the Middle Ages. It is suggested that haemorrhagic plague emerged from its animal host in Ethiopia and struck repeatedly at European/Asian civilisations, before appearing as the Black Death. The CCR5-Delta32 mutation confers protection against HIV-1 in an average of 10% of the people of European origin today. It is suggested that all the Deltaccr5 alleles originated from a single mutation event that occurred before 1000 BC and the subsequent epidemics of haemorrhagic plague gently forced up its frequency to 5 x 10(-5) at the time of the Black Death. Epidemics of haemorrhagic plague over the next three centuries then steadily raised the frequency in Europe (but not elsewhere) to present day values.

Disease Outbreaks↗

Lower phenytoin serum levels in persons switched from brand to generic phenytoin.

After generic phenytoin (PHT) was marketed, the authors identified eight adult patients (ages 34 to 49) whose seizures increased enough to require intervention after switching to generic PHT. The mean total PHT concentration on brand (before generic) was 17.7 +/- 5.3 mg/L, decreased to 12.5 +/- 2.7 mg/L with generic, and increased to 17.8 +/- 3.9 mg/L after brand was re-introduced. Brand and generic PHT do not yield equivalent concentrations in some patients and substitution should not be permitted without physician notification.

Adult↗

Meiotic defects in a man with non-obstructive azoospermia: case report.

Infertile men have an increased frequency of aneuploid sperm. We have determined that decreased recombination is associated with the production of aneuploid sperm in humans. The aim of this study was to determine whether some cases of infertility are associated with decreased meiotic recombination. Analysis of the early stages of meiosis was performed in a 33-year-old man with non-obstructive azoospermia. Newly developed immunocytogenetic techniques were used to identify the synaptonemal complex (SC) in various stages of prophase. Antibodies to meiotic proteins identified the SC (SYN1/SCP3), the centromere (CREST) and recombination sites (MLH1). Only 36 meiotic spreads were recovered from the infertile man, compared with hundreds available from controls. One-third of the cells were in zygotene compared with 4% in controls, demonstrating an inability of bivalents to synapse and progress to pachytene. The infertile man had a greatly reduced frequency of recombination, with a mean of only 32.7 MLH1 foci/cell (range 1-60) compared with 46.0 (range 21-62) in control donors. A high proportion of cells (73%) contained at least one autosomal bivalent with zero MLH1 foci, compared with only 4.5% in control donors. Discontinuities in the SC were also more prevalent (68% of cells versus 26% in controls). This is the first demonstration of dramatic pachytene-stage abnormalities in an infertile man using these powerful new immunocytogenetic techniques.

Adult↗

Paying attention to meaning.

Several paradigms show that responses to one event compromise responses to a second event for around 500 ms. Such effects are generally attributed to attentional capacity limitations associated with processing information in the first event. In a task in which targets could be distinguished only by their meaning, we varied the semantic relationship between distractors and targets following at different lags. Semantic relatedness alone produced a classic attentional blink. We conclude by discussing how attention theory might best accommodate these new effects.

Attention↗

Abnormal depolarizing patterns in three patients with filarial infection.

Several authors have described a particular potential of automated depolarization analysis in detecting malaria infection as part of the routine full blood count (FBC) performed by the Cell-Dyn 4000 analyzer. In these cases, abnormal depolarizing patterns are due to the presence of leukocyte-associated malaria hemozoin, a pigment which depolarizes the laser light. In this report we describe samples from three individual patients who did not have malaria infection but showed abnormal depolarizing events. Further investigation determined that these samples were from patients infected by the nematode Mansonella perstans. The observed depolarizing pattern consisted of a normal depolarizing eosinophil population and in addition an abnormal depolarizing population that showed a close "linear" relationship between "granularity" (90 degrees depolarization) and "lobularity" (90 degrees polarization). This atypical population was smaller than normal leukocytes and thus clearly different from the patterns associated with malaria infection. Abnormal depolarization patterns of M. perstans clearly do not reflect leukocyte-associated malaria hemozoin. It is possible however that the erythrocyte-lysing agent used to facilitate leukocyte analysis by the instrument may have caused microfilaria fragmentation and thus the distinctive "straight-line" features of the abnormal scatter plots

Blood Cell Count↗

LR-90 a new advanced glycation endproduct inhibitor prevents progression of diabetic nephropathy in streptozotocin-diabetic rats.

AIMS/HYPOTHESIS: Advanced glycation and lipoxidation endproducts have been implicated in the pathogenesis of diabetic complications, including diabetic nephropathy. LR-90, a new advanced glycation endproduct inhibitor, was investigated for its effects on the development of renal disease in diabetic rats. METHODS: Diabetic animals were randomly allocated into groups receiving LR-90 or vehicle (untreated). Age- and weight-matched non-diabetic rats were studied concurrently. Body weight, plasma glucose, glycated haemoglobin, urinary albumin and creatine excretions were measured serially. Kidney histopathology, AGE accumulation in cells and tissues, protein oxidation, were also examined. In vitro assays were used to assess the possible mechanism of action of LR-90. RESULTS: LR-90 inhibited the increase in albumin and creatinine concentrations, and concentrations of circulating AGE in diabetic rats without any effect on glycaemic control. LR-90 treated-rats also showed higher body weights than untreated diabetic rats. LR-90 prevented glomerulosclerosis, tubular degeneration and collagen deposition in the kidney. AGE-induced cross-linking and fluorescence of tail collagen were reduced by LR-90 treatment. LR-90 also decreased AGE accumulation in kidney glomeruli and nitrotyrosine deposition in the renal cortex. In vitro, LR-90 was capable of reacting with reactive carbonyl compounds and was a more potent metal chelator than pyridoxamine and aminoguanidine. CONCLUSION/INTERPRETATION: LR-90 reduces in vivo AGE accumulation, AGE-protein cross-linking and protein oxidation, and could be beneficial in preventing the progression of diabetic nephropathy. The AGE inhibitory and therapeutic effects of LR-90 could be attributed, at least in part, to its ability to react with reactive carbonyl species and/or potent metal chelating activity that inhibits glycoxidative-AGE formation.

Animals↗

Localized radiation increases morbidity and mortality after TBI-containing autologous stem cell transplantation in patients with lymphoma.

The purpose of this study is to assess the relationship between involved field radiation therapy (IFRT) and treatment-related morbidity and mortality in patients receiving high-dose chemotherapy (HDC), total body irradiation (TBI) and autologous peripheral stem cell transplant (PSCT) for Hodgkin's and non-Hodgkin's lymphoma. Between January 1994 and May 2002, 156 patients underwent HDC, TBI and autologous PSCT. Localized external beam radiation therapy was given to 21 patients for consolidation, or to achieve control of symptomatic or active disease prior to or after transplant. Among patients who had IFRT prior to autologous PSCT, five treatment-related deaths were observed, compared to seven deaths in 135 patients who had autologous PSCT without IFRT (P<0.01). Most deaths were attributable to sepsis and multiorgan failure. A higher incidence of pneumonitis was also noted in patients exposed to mediastinal irradiation. No adverse impact on long-term survival could be demonstrated. Involved field radiation prior to TBI is associated with higher treatment-related mortality in lymphoma patients undergoing autologous peripheral stem cell transplant, necessitating careful monitoring.

Adult↗

A comparison of physician and patient perception of the problems of habitual snoring.

Assumptions are often made by doctors about the nature of the impact of uncomplicated snoring. The aim of this study was to provide a comprehensive view of the problems experienced by snoring patients, and to compare these with the perceptions of otolaryngologists. Part 1: 121 snorers and 419 otolaryngologists completed open-ended problems lists; Part 2: 56 snorers and 63 matched controls completed a mood questionnaire and the Golombok Rust Inventory of Marital State (GRIMS.) There was a clear agreement between snorers and otolaryngologists that sleep-related difficulties comprise the most frequent category of problems that may result from snoring. Snorers report a significantly greater number of physical problems and significantly fewer relationship problems than perceived by otolaryngologists. GRIMS scores were similar in patients and controls. Snorers, however, were significantly more depressed. Doctors appear to address snoring from the twin perspectives of damaged relationships and possible sleep apnoea. Their patients are more concerned about disturbing the sleep of others, and are subject to low mood. The snorers' 25 different responses are now being used as the basis for a Snoring Symptom Index.

Attitude↗

Whiplash: a biochemical study of muscle injury.

Outcome following whiplash injury of the cervical spine is variable, and the pathology of those with prolonged symptoms is uncertain. We undertook a prospective study in 25 patients to identify whether those with prolonged symptoms following whiplash injury exhibit a rise in serum creatine kinase consistent with significant muscle damage at the time of injury. Transient rise in creatine kinase level was seen in only 2 of 25 patients, neither of whom complained of prolonged symptoms. Of the 8 patients who developed chronic symptoms following whiplash injury, none demonstrated a serum creatine kinase rise. Prolonged symptoms following whiplash injury cannot be explained by biochemically measurable muscle damage.

Adult↗