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Biomedical subjects

P Smyth

Publications and source records attributed to P Smyth.

18 recordsLinked to original sources
PubMed2000

Hydrolysed casein diet protects BB rats from developing diabetes by promoting islet neogenesis.

Feeding diabetes-prone BioBreeding (BBdp) rats a hydrolysed-casein (HC)-based semi-purified diet results in two-to-three-fold fewer diabetes cases compared with feeding cereal-based diets such as NIH-07 (NIH). We showed previously that young NIH-fed BBdp rats had decreased islet area at a time when classic insulitis was minimal. Rats fed an HC diet maintained near normal islet area followed 3-4 weeks later by a deviation of the pancreas cytokine pattern from Th1 to Th2/Th3. This finding raised the possibility that BBdp rats were more susceptible to diet-induced changes in islet homeostasis. To investigate this possibility further, BBdp rats were fed an NIH or HC diet from days 23 to 45. Bouin's fixed sections of pancreas were stained with H & E or antibodies for insulin and glucagon. Cell proliferation nuclear antigen (PCNA) was used as a marker of cell proliferation and cells were stained for putative markers of islet neogenesis, cytokeratin 20 (CK20) and Bcl-2. Apoptotic bodies were recognized by morphological features and by TUNEL-positive staining. BBdp rats fed an HC diet had a significantly higher beta-cell fraction than rats fed NIH, whereas alpha-cell fraction and beta-cell size were not affected by diet or rat type. Apoptotic bodies of beta-cells were rare and unaffected by diet. The number of PCNA(+)beta-cells was not affected by diet. CK20 expression was localized in the ductular system and at the periphery of islets in rats aged 7 and 45 days. There were more CK20(+)islets in BBdp rats fed NIH than in those fed HC but the CK20 area fraction was unaffected by diet. Bcl-2 expression was scattered among ducts and central acinar cells. The number of extra-islet insulin(+)and glucagon(+)clusters (<four cells) was significantly higher in animals fed the HC diet compared with those fed NIH. Most of the insulin(+)clusters were also homeodomain-containing transcription factor pancreas duodenum homeobox gene-1 (PDX-1) positive. Glucagon(+)/PDX-1(+)clusters were rarely found. These data are consistent with a shift in pancreas homeostasis that maintains islet cell mass by increased islet neogenesis, a process that was enhanced in animals fed a diabetes-retardant diet.

Animals↗
PubMed2000

Data mining: data analysis on a grand scale?

Modern data mining has evolved largely as a result of efforts by computer scientists to address the needs of 'data owners' in extracting useful information from massive observational data sets. Because of this historical context, data mining to date has largely focused on computational and algorithmic issues rather than the more traditional statistical aspects of data analysis. This paper provides a brief review of the origins of data mining as well as discussing some of the primary themes in current research in data mining, including scalable algorithms for massive data sets, discovering novel patterns in data, and analysis of text, web, and related multimedia data sets.

Algorithms↗
PubMed1999

Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters.

OBJECTIVE: TGPO autoantibodies (aAbs) that bind simultaneously to thyroglobulin (Tg) and thyroperoxidase (TPO) are present in the serum of patients with autoimmune thyroid diseases (AITD) and have been found to differ from monospecific Tg and TPO aAbs. To obtain further insights on the prevalence defined as the rate of occurrence and significance of TGPO aAbs in a large population, we carried out a collaborative study involving 15 European teams. METHODS: Serum samples from 3122 patients with various thyroid and non-thyroid diseases and normal subjects were assayed using a novel TGPO aAb detection kit. This test was designed so that TGPO aAbs are trapped between the Tg-coated solid phase and the soluble TPO labeled with a radioiodinated monoclonal antibody. RESULTS: Only three out of the 220 normal subjects (prevalence of 1.4%) were found to have positive TGPO aAb levels, which were mainly observed in the patients with AITD: the group of patients suffering from Hashimoto's thyroiditis had a TGPO aAb prevalence of 40.5% (n=437 patients), those with Graves' disease, a prevalence of 34.6% (n=645) and those with post-partum thyroiditis, 16.0% (n=243). Among the non-AITD patients with positive TGPO aAb levels, the TGPO aAb prevalence ranged from 20.7% among those with thyroid cancer (n=246) to 0% among those with toxic thyroid nodules (n=47). Among the patients with non-thyroid diseases, the TGPO aAb prevalence ranged from 9.8% in the case of Biermer's pernicious anemia (n=78) to 0% in that of premature ovarian failure (n=44). It is worth noting that the groups showing the highest TGPO aAb prevalence also contained the patients with the highest TGPO aAb titers. Statistical comparisons between the TGPO aAb prevalences in the various groups showed that TGPO aAb could be used as a parameter to distinguish between the groups of Hashimoto's and Graves' patients and between the women with post-partum thyroiditis and the post-partum women with only Tg and/or TPO aAb established during early pregnancy. Unexpectedly, the correlations between TGPO aAbs and Tg and TPO aAbs were found to depend mainly on the assay kit used. CONCLUSION: High TGPO aAb titers are consistently associated with AITD but the reverse was not found to be true. TGPO aAbs are a potentially useful tool, however, for establishing Hashimoto's diagnosis, and would be worth testing in this respect with a view to using them for routine AITD investigations.

Autoantibodies↗
PubMed1997

Model-based interpretation of complex and variable images.

The ultimate goal of machine vision is image understanding-the ability not only to recover image structure but also to know what it represents. By definition, this involves the use of models which describe and label the expected structure of the world. Over the past decade, model-based vision has been applied successfully to images of man-made objects. It has proved much more difficult to develop model-based approaches to the interpretation of images of complex and variable structures such as faces or the internal organs of the human body (as visualized in medical images). In such cases it has been problematic even to recover image structure reliably, without a model to organize the often noisy and incomplete image evidence. The key problem is that of variability. To be useful, a model needs to be specific-that is, to be capable of representing only 'legal' examples of the modelled object(s). It has proved difficult to achieve this whilst allowing for natural variability. Recent developments have overcome this problem; it has been shown that specific patterns of variability in shape and grey-level appearance can be captured by statistical models that can be used directly in image interpretation. The details of the approach are outlined and practical examples from medical image interpretation and face recognition are used to illustrate how previously intractable problems can now be tackled successfully. It is also interesting to ask whether these results provide any possible insights into natural vision; for example, we show that the apparent changes in shape which result from viewing three-dimensional objects from different viewpoints can be modelled quite well in two dimensions; this may lend some support to the 'characteristic views' model of natural vision.

Form Perception↗
PubMed1997

Probabilistic independence networks for hidden Markov probability models.

Graphical techniques for modeling the dependencies of random variables have been explored in a variety of different areas, including statistics, statistical physics, artificial intelligence, speech recognition, image processing, and genetics. Formalisms for manipulating these models have been developed relatively independently in these research communities. In this paper we explore hidden Markov models (HMMs) and related structures within the general framework of probabilistic independence networks (PINs). The paper presents a self-contained review of the basic principles of PINs. It is shown that the well-known forward-backward (F-B) and Viterbi algorithms for HMMs are special cases of more general inference algorithms for arbitrary PINs. Furthermore, the existence of inference and estimation algorithms for more general graphical models provides a set of analysis tools for HMM practitioners who wish to explore a richer class of HMM structures. Examples of relatively complex models to handle sensor fusion and coarticulation in speech recognition are introduced and treated within the graphical model framework to illustrate the advantages of the general approach.

Algorithms↗
PubMed1997

Zinc, copper and iron levels in tissues of the vitamin B6 deficient rat.

Tissue zinc (Zn), copper (Cu) and iron (Fe) were determined in three groups of young male Wistar rats that received a daily pyridoxine hydrochloride (PN.HCl) intake of 45, 23 and 0 micrograms respectively in their diets over 8 weeks. No significant differences were found in the Zn and Cu levels in the liver, kidney, skeletal and cardiac tissue of all 3 groups. The Fe levels were significantly higher in the heart and liver and significantly lower in the skeletal muscle of the group receiving no PN.HCl in the diet (P < 0.05). This study indicates that the increased fecal excretion of Zn and Cu observed during a previous balance study on the above vitamin B6 deficient group of animals may be due to a decreased absorption of these elements from the diet rather than their excretion from tissue stores. The changes in Fe levels in the heart, liver and skeletal muscle points towards some alteration in tissue stores of this element during a vitamin B6 deficiency.

Animals↗
PubMed1994

Hypothyroidism secondary to topical iodine treatment in infants with spina bifida.

Four infants with spina bifida, who had not undergone surgical closure of a lumbar myelomeningocele, were assessed and investigated for hypothyroidism. From birth, all were treated once daily with an iodine-containing ointment (Betadine) as a local antiseptic applied to the spina defect. All infants showed excess urinary iodine concentration. Two infants, without clinical evidence of hypothyroidism or goitre, showed low serum free thyroxine and high thyroid stimulating hormone concentrations at a mean age of four weeks and were started on thyroxine replacement treatment. Betadine ointment and thyroxine were stopped simultaneously at a mean age of nine months, following which all infants remained euthyroid. Thyroid function tests should be monitored routinely if iodine is applied as a topical antiseptic to infants.

Administration, Topical↗
PubMed1988

24-hour control of blood pressure by once daily doxazosin: a multicentre double-blind comparison with placebo.

The antihypertensive efficacy of the new, once daily, alpha 1-adrenoceptor inhibitor, doxazosin, was compared with placebo in 40 patients with mild to moderate hypertension. Following a dose titration the mean final daily doxazosin dose in 20 patients was 13.1 mg. Through-the-day blood pressure control was assessed by frequent measurements during 24 h hospitalisation in the 9 th week of double-blind treatment compared with similar measurements made during a 2 week single-blind placebo run-in. Mean reductions in standing and supine systolic and diastolic blood pressure during doxazosin treatment were statistically significantly greater than during placebo treatment at most hourly time points during the 24 h post-dose period. Twenty-four post-dose the mean falls in standing and supine diastolic blood pressure during doxazosin treatment were statistically significant when compared with placebo. Adverse effects during doxazosin treatment were generally minor and were tolerated or disappeared with continued therapy. No patients were withdrawn from the study due to adverse effects. We conclude that once daily doxazosin provides smooth and effective blood pressure control throughout a 24 h post-dose period.

Adult↗
PubMed1985

A test of cognitive vulnerability in individuals prone to depression.

Recovered unipolar depressed patients were compared with recovered anxious and non-psychiatric controls in depressed and neutral mood induction conditions to test the hypothesis that depression-prone individuals would demonstrate more negative cognitions with mild mood changes. Only the non-psychiatric controls showed significant mood changes and the hypothesis was not supported.

Adult↗
PubMed1985

Milrinone in heart failure. Acute effects on left ventricular systolic function and myocardial metabolism.

Milrinone, a new bipyridine compound related to amrinone, is a potent non-adrenergic inotrope in experimental preparations and also shows vasodilator activity. In the present study the haemodynamic and metabolic effects of milrinone were evaluated in 12 patients with congestive heart failure. Milrinone 5 mg given orally produced a sharp reduction in left ventricular end diastolic pressure without significantly affecting stroke volume. The improvement in left ventricular function was due to a combination of vasodilation and positive inotropism. Thus small reductions in blood pressure and systemic vascular resistance were associated with increments in the isovolumic indices of left ventricular function. The relation between left ventricular end systolic pressure and dimension was displaced leftwards and downwards. Only reductions in left ventricular cavity dimension were statistically significant, however. Though myocardial oxygen consumption did not change significantly, it tended to increase whereas lactate consumption tended to decrease. This trend towards oxygen imbalance suggests the need for caution in the use of milrinone in patients with severe coronary artery disease.

Adult↗
PubMed1985

Milrinone in heart failure. Effects on exercise haemodynamics during short term treatment.

The effects of milrinone, a new bipyridine inotropic agent, on the haemodynamic responses to treadmill exercise were studied in 12 patients with congestive heart failure. Four weeks' treatment with milrinone 20 mg daily produced an improvement in left ventricular function during exercise as reflected by significant increments in cardiac index and stroke volume index without change in pulmonary capillary wedge pressure. Systemic oxygen consumption, measured at submaximal exercise, also increased suggesting that the drug induced rise in stroke output was associated with improved skeletal muscle perfusion. Maximum exercise capacity increased. Importantly, the beneficial effects of milrinone on exercise haemodynamics and exercise tolerance were sustained throughout the four week treatment period. No drug related side effects occurred. After treatment with milrinone was stopped left ventricular function deteriorated to a level slightly, but significantly, worse than that before treatment. These observations indicate a potentially useful role for milrinone in treating heart failure.

Adult↗
PubMed1984

Restoration of normal reflex responses to orthostatic stress during felodipine therapy in congestive heart failure.

The mechanisms underlying the abnormal responses to orthostatic stress in congestive heart failure are ill defined and little is known about the effects of specific therapy. In the present study intravascular pressures and plasma noradrenaline levels were measured in nine patients with heart failure subjected to 45 degrees and 90 degrees upright tilt. Studies were repeated during 4 weeks of vasodilator therapy with felodipine and again after felodipine withdrawal. Before the introduction of vasodilator therapy, tilt did not activate orthostatic reflexes despite significant reductions in left ventricular filling pressure and cardiac output. Thus, plasma noradrenaline, heart rate and systemic vascular resistance were unaffected and blood pressure fell. Felodipine resulted in a rapid and sustained improvement in left ventricular function but restoration of orthostatic reflexes was delayed and could be detected only after 48 h therapy. At this time, and during the subsequent 4 weeks, tilt-induced reductions in ventricular filling and cardiac output produced a normal rise in plasma noradrenaline and heart rate. A postural drop in blood pressure, however, was not averted because the direct action of felodipine on vascular smooth muscle prevented adrenergically-mediated increments in systemic vascular resistance. Felodipine withdrawal led to a prompt deterioration in left ventricular function. Orthostatic reflexes, however, were still intact 48 h later when tilt elicited a completely normal pattern of responses. These observations confirm that the abnormal responses to orthostatic stress in congestive heart failure are due principally to impairment of autonomic control mechanisms and are not related to the absence of venous pooling. Importantly the autonomic dysfunction is reversible with felodipine therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Effects of vasodilator treatment with felodipine on haemodynamic responses to treadmill exercise in congestive heart failure.

Treatment with vasodilators in heart failure has not always produced a useful improvement in the haemodynamic responses to exercise, and in many cases early drug tolerance has further limited the potential of this type of treatment. In a study to evaluate the efficacy of felodipine, a new calcium antagonist with selective vasodilator properties, in the management of congestive heart failure 10 patients with congestive heart failure underwent treadmill exercise testing before and during oral treatment with felodipine 30 mg daily. At every level of exercise felodipine lowered the pulmonary capillary wedge pressure, whereas cardiac index and stroke index increased considerably. The haemodynamic improvement was associated with an increase in the duration of exercise to exhaustion. Importantly, these beneficial effects were sustained throughout four weeks of treatment without evidence of drug tolerance. These observations suggest a useful role for felodipine in the long term management of congestive heart failure.

Adult↗