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Biomedical subjects

S Lloyd

Publications and source records attributed to S Lloyd.

At least 19 recordsLinked to original sources

Nicotinic and muscarinic cholinergic receptor binding in the human hippocampal formation during development and aging.

High-affinity nicotine, alpha-bungarotoxin (alpha BT) and muscarinic receptor binding was measured in the human hippocampal formation in a series of 57 cases aged between 24 weeks gestation and 100 years. Changes in nicotine receptor binding during development and aging were more striking than differences in alpha BT and muscarinic binding. Nicotine binding was higher at the late foetal stage than at any other subsequent time in all areas investigated. In the hippocampus a fall in binding then occurred within the first six months of life, with little or no subsequent fall during aging, whereas in the entorhinal cortex and the presubiculum the major loss of nicotine binding occurred after the fourth decade. alpha BT binding was significantly elevated in the CA 1 region, but in no other region of the hippocampus, in the late foetus, and there was also a fall in alpha BT binding in the entorhinal cortex during aging from the second decade. The modest changes in total muscarinic binding, which appeared to reflect those in M1 and M3 + 4 rather than M2 binding, were a rise in the entorhinal cortex between the foetal stage and childhood and a tendency for receptors to fall with age in the hippocampus and subicular complex. These findings implicate mechanisms controlling the expression of nicotinic receptors to a greater extent than muscarinic receptors in postnatal development and aging in the human hippocampus.

Adolescent

Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom.

BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.

4-Butyrolactone

Measurement and metabolism of isoflavonoids and lignans in the human male.

Asian men, who consume a low fat/high fibre soya-based diet, have very much lower incidence of prostate cancer than men from North America and Europe. The soya bean is a rich source of the isoflavonic phyto-oestrogens, daidzein, genistein and equol, compounds which may be cancer-protective in Asian populations. The lignans, enterolactone and enterodiol, plant oestrogens derived from cereals and vegetables, may act in a similar manner in vegetarian men. We report here on the measurement of isoflavonoids and lignans, by gas chromatography-mass spectrometry, in prostatic fluid of men from Asia and Europe and also on the metabolism of these compounds in Western men following dietary supplementation.

Adult

Pattern of Cryptosporidium parvum oocyst excretion by experimentally infected dogs.

Six 6-week-old Beagle dogs were fed Cryptosporidium parvum oocysts of calf origin. All 6 dogs shed oocysts in faeces. Greater numbers of oocysts were detected with a Weber concentration technique (formalin-ethyl acetate extraction and NaCl centrifugal flotation) stained with either fluorescent antibody or modified Ziehl-Neelsen than with other formalin-ether or -ethyl acetate extraction methods. Oocyst numbers g-1 of faeces rose from days 3 to 5 to a first and highest peak lasting to days 7-9, and 5 of the 6 dogs passed oocysts for at least 80 days. However, the numbers of oocysts detected in the dogs' faeces were low, only 16.1% of the samples in the first month after infection and 2.5% thereafter contained > or = 10000 oocysts g-1 of faeces. Oocyst production was cyclical, with 19.3% of samples negative in the first month after infection and 42.5% thereafter.

Animals

Nicotinic receptor distribution in the human thalamus: autoradiographical localization of [3H]nicotine and [125I] alpha-bungarotoxin binding.

The thalamus plays a major role in relaying and transforming information that is relayed to the cortex and in turn modulates cortical outputs. The reticular nucleus projects to the other thalamic nuclei, modulating and integrating their activity. The distribution of high affinity nicotine and alpha-bungarotoxin (alpha BTX) receptors in the human thalamus has been investigated by radioligand autoradiography in post mortem human tissue. [3H]nicotine binding in the human thalamus was high in most thalamic nuclei, especially in the lateral dorsal, the medial geniculate, lateral geniculate and anterior nuclei. The distribution of [125I] alpha BTX binding was quite distinct from [3H]nicotine binding. [125I] alpha BTX binding was generally lower (< 0.26-11.62 fmol/mg protein compared with 6.68-36.17 fmol/mg protein for nicotine binding) and concentrated in the reticular nucleus, with discrete groups of cells displaying higher binding in the latter. These results indicate differences between the distribution of nicotinic receptors in humans and those previously reported in mice and monkeys. Changes in high affinity nicotine and alpha BTX receptors in the thalamus may contribute to symptoms observed in neuropathological conditions associated with disorders of perception and movement such as Dementia with Lewy Bodies, Alzheimer's Disease and Schizophrenia.

Adult

D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele.

The relationship between a dopamine D2 receptor genetic polymorphism at the Taq1 A locus and the level of D2 receptor binding was investigated in normal, middle aged to elderly subjects with no psychiatric or neurological disorders. D2 receptor binding was measured by autoradiography in the caudate, putamen and nucleus accumbens, using the specific D2 receptor ligand [3H]-raclopride. In a sample of 44 individuals, only one was homozygous for the A1 allele, 25 were homozygous for A2 and 18 were heterozygotes. The presence of one or two A1 alleles was associated with reduced D2 receptor binding in all areas of the striatum, reaching statistical significance in the ventral caudate and putamen (p = 0.01 and p = 0.044, respectively). This reduction was more marked in males than females, particularly in the putamen. A genetic predisposition to lower D2 receptor expression may increase susceptibility to neuroleptic medication or clinical symptoms that are associated with diseases involving dopaminergic pathology.

Aged

Widespread geographic distribution of oral Candida dubliniensis strains in human immunodeficiency virus-infected individuals.

Candida dubliniensis is a recently identified chlamydospore-positive yeast species associated with oral candidiasis in human immunodeficiency virus (HIV)-infected (HIV+) patients and is closely related to Candida albicans. Several recent reports have described atypical oral Candida isolates with phenotypic and genetic properties similar to those of C. dubliniensis. In this study 10 atypical chlamydospore-positive oral isolates from HIV+ patients in Switzerland, the United Kingdom, and Argentina and 1 isolate from an HIV-negative Irish subject were compared to reference strains of C. albicans and Candida stellatoidea and reference strains of C. dubliniensis recovered from Irish and Australian HIV+ individuals. All 11 isolates were phenotypically and genetically similar to and phylogenetically identical to C. dubliniensis. These findings demonstrate that the geographical distribution of C. dubliniensis is widespread, and it is likely that it is a significant constituent of the normal oral flora with the potential to cause oral candidiasis, particularly in immunocompromised patients.

AIDS-Related Opportunistic Infections

Decreased [3H]ouabain binding sites in skeletal muscle of rats with chronic heart failure.

Abnormalities intrinsic to skeletal muscle are thought to contribute to decrements in exercise capacity found in individuals with chronic heart failure (CHF). Na+-K+-adenosinetriphosphatase (the Na+ pump) is essential for maintaining muscle excitability and contractility. Therefore, we investigated the possibility that the number and affinity of Na+ pumps in locomotor muscles of rats with CHF are decreased. Myocardial infarction (MI) was induced in 8 rats, and a sham operation was performed in 12 rats. The degree of CHF was assessed approximately 180 days after surgery. Soleus and plantaris muscles were harvested, and Na+ pumps were quantified by using a [3H]ouabain binding assay. At the time of muscle harvest, MI and sham-operated rats were similar in age (458 +/- 54 vs. 447 +/- 34 days old, respectively). Compared with their sham-operated counterparts, MI rats had a significant amount of heart failure, right ventricular-to-body weight ratio was greater (48%), and the presence of pulmonary congestion was suggested by an elevated lung-to-body weight ratio (29%). Left ventricular end-diastolic pressure was significantly increased in the MI rats (11 +/- 1 mmHg) compared with the sham-operated controls (1 +/- 1 mmHg). In addition, mean arterial blood pressure was lower in the MI rats compared with their control counterparts. [3H]ouabain binding sites were reduced 18% in soleus muscle (136 +/- 12 vs. 175 +/- 13 pmol/g wet wt, MI vs. sham, respectively) and 22% in plantaris muscle (119 +/- 12 vs. 147 +/- 8 pmol/g wet wt, MI vs. sham, respectively). The affinity of these [3H]ouabain binding sites was similar for the two groups. The relationship between the reduction in Na+ pump number and the reduced exercise capacity in individuals with CHF remains to be determined.

Animals

Universal Quantum Simulators

Feynman's 1982 conjecture, that quantum computers can be programmed to simulate any local quantum system, is shown to be correct.

Journal Article

Nurses taking on junior doctors' work: a confusion of accountability.

The number of hospital based posts in which nurses take over clinical work previously done by junior doctors is growing. Accountability for the scope of such new roles and the standards of practice which apply to them are still unclear. When analysed together and compared, the regulations arising from the professional bodies (GMC and UKCC), civil law concerning certain wrongs to patients, and employment law are sometimes contradictory and hard to interpret. The resulting uncertainties about appropriate management for clinical roles evolving between the professions, coupled with an increasingly litigious public, put the nurses and consultants involved at risk of complaints and of disciplinary and legal action. Drawing on our current research into changing clinical roles at the medical-nursing interface, we suggest strategies to reduce risk. Doctors and nurses should be equal partners in planning and managing these new posts, patients should be informed adequately about the nature of the postholder's role and training, significant changes in the work of such postholders should be formally acknowledged by the employer and relevant insurers, individuals taking up new roles should have access to legal advice and support to cover legal risk, and national regulatory bodies need to work together to harmonise their codes of practice in relation to changing clinical roles between the professions.

Humans

Beta-amyloidosis in normal aging and transmitter signaling in human temporal lobe.

Interactions between abnormal amyloid precursor protein metabolism and cholinergic dysfunction are increasingly apparent. Both of these major features of Alzheimer's disease occur in restricted loci in normal aging--a potential model for early Alzheimer type pathology. Entorhinal cortex is particularly vulnerable to beta-amyloidosis and compared with other cortical areas is remarkable for the relatively high density of nicotinic (3H-nicotine) but not other cholinergic or glutamate receptor binding. With increasing age, post-maturity, there is a persistent decline in nicotinic receptor binding in entorhinal cortex whereas muscarinic M1 and non-M1, glutamate NMDA and non-NMDA receptors are spared. Normal elderly individuals, distinguished by the absence of beta A4 immunoreactive plaques in this area, are differentiated from those with plaques by higher nicotine binding. Amongst individuals with an established history of smoking tobacco, nicotinic receptor binding and hippocampal choline acetyltransferase were elevated compared with non-smokers and preliminary evidence indicates a reduced density of cortical plaques. These findings are consistent with the hypothesis that down regulation of the nicotinic cholinergic receptor--a ligand gated calcium channel known to control the expression of neurotrophins--plays a role in the evolution of Alzheimer-type pathology.

Adolescent

Establishing equivalence between scaled measures of quality of life.

In this paper, methodologies which have been used in the pharmaceutical industry to demonstrate the equivalence of drug preparations, are applied to the measurement of quality of life (QOL). This approach is feasible when the generated data are measured on the same scale. Data from the quality of life instruments are transformed into interval scales by means of an appropriate scaling procedure. It is demonstrated that equivalence of QOL instruments is linked by a linear relationship between the QOL instruments Functional Assessment of Cancer Therapy (FACT) and the Functional Living Index-Cancer (FLIC). The linear relationship is derived using orthogonal least squares regression which takes into account that both measures are subject to error.

Activities of Daily Living

Rates of reinfection with Echinococcus granulosus, Taenia hydatigena, taenia ovis and other cestodes in a rural dog population in Uruguay.

A survey was undertaken to determine both the prevalence of, and reinfection rates with Echinococcus granulosus and other cestodes in the Department of Florida, Uruguay. Baseline prevalence was determined in 303 rural dogs which then, in 4 groups, were re-examined 2, 4, 8 or 12 months later. Baseline prevalences for E. granulosus, Taenia hydatigena, Taenia ovis and Dipylidium caninum were 13.2, 13.9, 2.3 and 13.2%, respectively. The frequency distribution of E. granulosus was over-dispersed. Dogs in the population became infected with E. granulosus between 2 and 4 months after treatment (prevalences at 2, 4, 8 and 12 months were 0, 6.8, 18.6 and 27.9%, respectively). There was no indication that there was a predisposition of dogs to infection with the Odds Ratio being 1.0. Dogs were infected with T. hydatigena and D. caninum within 2 months and with T. ovis between 2 and 4 months after treatment. The implications of these different rates of reinfection in the dog population on anthelmintic control strategies against cystic echinococcosis are discussed.

Age Factors

Familial breast cancer: a controlled study of risk perception, psychological morbidity and health beliefs in women attending for genetic counselling.

The present study set out to evaluate perceptions of risk, psychological morbidity and health behaviours in women with a family history of breast cancer who have attended genetic counselling and determine how these differ from general population risk women. Data were collected from 62 genetic counselees (cases) attending the Royal Marsden and Mayday University Hospital genetic counselling services and 62 matched GP attenders (controls). Levels of general psychological morbidity were found to be similar between cases and controls; however, cases reported significantly higher breast cancer-specific distress despite clinic attendance [mean (s.d.) total Impact of Event Scale score, 14.1 (14.3) cases; 2.4 (6.7) controls, P < 0.001]. Although cases perceived themselves to be more susceptible to breast cancer, many women failed correctly to recall risk figures provided by the clinic; 66% could not accurately recall their own lifetime chance. Clinics appeared to have a positive impact on preventive behaviours and cases tended to engage more regularly in breast self-examination (monthly, 66% of cases vs 47% of controls), although few differences were found between groups in terms of health beliefs. We conclude that counselees and GP controls showed considerable similarities on many of the outcome measures, and risk of breast cancer was not predictive of greater psychological morbidity; although cases were more vulnerable to cancer-specific distress. Despite genetic counselling, many cases continued to perceive their risk of breast cancer inaccurately.

Adult

Validation of the functional assessment of multiple sclerosis quality of life instrument.

Based on scientific literature and interviews with clinicians and patients, we developed a quality of life instrument for use with people with MS called the Functional Assessment of Multiple Sclerosis (FAMS). The initial item pool consisted of 88 questions: 28 from the general version of the Functional Assessment of Cancer Therapy quality of life instrument, plus 60 generated by patients, providers, and literature review. The validation samples comprised a mail survey cohort (N = 377) and a clinical cohort (N = 56). Both cohorts provides evidence for internal consistency of the derived subscales, test-retest reliability, content validity, concurrent validity, and construct validity. Principal components and Rasch measurement model analyses were applied sequentially to survey sample data, reducing test length to 44 questions, divided into six subscales: mobility, symptoms, emotional well-being (depression), general contentment, thinking/fatigue, and family/social well-being. Fifteen initially rejected questions were added back as miscellaneous (unscored) questions for their potential clinical and empirical value. The mobility subscale was strongly predictive of the Kurtzke Extended Disability Status Scale and the Scripps Neurologic Rating Scales. The other five subscales were not, indicating they measure aspects of patient quality of life not captured by the neurologic exam. The final 59-item English language instrument (FAMS version 2) is available for inclusion in clinical trials and clinical practice.

Adult

Teething in babies: separating fact from fiction.

In one study, out of 50 babies hospitalised for symptoms attributed to teething, 48 had an organic cause of illness. Symptoms may include a slight rise in temperature, disturbed sleep and feeding, irritability, swollen tender gums and dribbling. Diarrhoea, respiratory symptoms, pulling at the ears, fever or convulsions should not be attributed to teething and require medical attention.

Child, Preschool