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At least 235 records · Page 13Linked to original sources

PubMed2004

Impact of primary surgery on pituitary function in patients with non-functioning pituitary adenomas -- a study on 721 patients.

INTRODUCTION: The aim of this study was to define the impact of surgery on pituitary function in a large consecutive series of patients harbouring non-functioning pituitary adenomas. MATERIALS AND METHOD: Between December 1982 and December 2000, a total of 822 patients underwent primary surgery in the authors' department. In 721 cases a complete set of endocrinological data was available. Functions of the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes were assessed immediately before surgery and again one week, 3 months and 1 year after the operation, utilizing standardized tests and commercially available assays. RESULTS: There was some degree of pre-operative hypopituitarism in 561 (85%) and 53 (86.3%) of the patients belonging to the transsphenoidal and the transcranial groups, respectively. Prior to transsphenoidal [transcranial] surgery, 163 (31%) [34 (55.7%)] of the patients had secondary adrenal deficiency, 463 (76.6%) [49 (89%)] had hypogonadism and 105 (19.1%) [14 (25.4%)] were hypothyroid. Preoperatively, prolactin levels were mildly elevated in 167 patients (25.3%), whereas 1 year after surgery, levels were elevated in only 5 patients. Permanent diabetes insipidus occurred in 4 patients, 2 from the transsphenoidal group (0.3%) and 2 from the transcranial group (3.2%). Following transsphenoidal surgery 110 (19.6%) of patients had normal pituitary function [versus 0% after transcranial surgery], 169 (30.1%) [6 (11.3%)] showed improvement, 274 (48.9%) [49 (73.7%)] had persistent deficits and 8 (1.4%) [8 (15%)] showed deterioration of pituitary function. DISCUSSION: These data indicate that transsphenoidal surgery for non-functioning pituitary adenomas in expert hands is, relatively, far less detrimental to patients compared with transcranial surgery. The latter carries a much greater risk of post-operative deterioration in pituitary function.

Adenoma↗

PubMed2005

Conservation of the E-function for floral organ identity in rice revealed by the analysis of tissue culture-induced loss-of-function mutants of the OsMADS1 gene.

Rapid progress in studies on flower development has resulted in refining the classical 'ABC model' into a new 'ABCDE model' to explain properly the regulation of floral organ identity. Conservation of E-function for flower organ identity among the dicotyledonous (dicot) plants has been revealed. However, its conservation in monocotyledonous (monocot) plants remains largely unknown. Here, we show the conservation of E-function in rice (Oryza sativaL.) by characterizing tissue culture-induced mutants of two MADS-box genes, OsMADS1and OsMADS5, which form a subclade within the well-supported clade of SEP-genes (E-function) phylogeny. Severe loss-of-function mutations of OsMADS1cause complete homeotic conversion of organs (lodicules, stamens, and carpels) of three inner whorls into lemma- and palea-like structures. Such basic deformed structure is reiterated along with the pedicel at the center of the same floret, indicating the loss of determinacy of the flower meristem. These phenotypes resemble the phenotypes caused by mutations of the dicot E-class genes, such as the Arabidopsis SEP123(SEPALLATA1/2/3) and the petunia FBP2(Floral Binding Protein 2), suggesting that OsMADS1play a very similar role in rice to that of defined E-class genes in dicot plants. In case of the loss-of-function mutation of OsMADS5, no defect in either panicles or vegetative organs was observed. These results demonstrate that OsMADS1clearly possesses E-function, and so, E-function is fundamentally conserved between dicot plants and rice, a monocot model plant.

Alleles↗

PubMed2006

Left ventricular diastolic function and endothelial function in patients with erectile dysfunction.

The aim of this study was to assess left ventricular diastolic function and forearm endothelial function in patients with erectile dysfunction (ED) without overt cardiovascular disease. Forearm endothelial function and diastolic Doppler parameters, including tissue Doppler imaging, were studied in 32 men with ED and 27 age-matched, healthy, male control subjects. Left ventricular diastolic function in patients with ED and the relation between endothelium-dependent vasodilation and the Doppler parameters of left ventricular diastolic function, including tissue Doppler imaging, were assessed. Endothelium-dependent vasodilation (4.1+/-3.3% vs 9.7+/-4.2%, p<0.001) as well as the mitral inflow E velocity (0.66+/-0.17 vs 0.80+/-0.16 m/s, p=0.01), the E/A ratio (the ratio of mitral inflow E velocity to mitral inflow A velocity; 0.91+/-0.3% vs 1.22+/-0.26%, p<0.001), and the E/Em ratio (the ratio of mitral A-wave velocity to early diastolic velocity in the annulus derived by tissue Doppler imaging; 7.4+/-2.7% vs 6.6+/-1.6%, p=0.03) were smaller in the ED group than in the control group. Deceleration time (228.6+/-61.6 vs 192.9+/-44.6 ms, p=0.03) and isovolumetric relaxation time (112.8+/-18 vs 94+/-15.9 ms, p<0.001) were also prolonged in the ED group compared with the control group. The mitral E-wave velocity (r=0.40, p=0.022), the E/A ratio (r=0.40, p=0.027), and the E/Em ratio (r=-0.52, p= 0.003) were related to endothelium-dependent vasodilation by nivariate analysis. Only the E/Em ratio was correlated with endothelium-dependent vasodilation by multivariate analysis. In conclusion, this study indicates that endothelial function and left ventricular diastolic function are impaired in patients with ED without overt cardiovascular disease.

Blood Flow Velocity↗

PubMed2004

Prediction of functional sites in proteins using conserved functional group analysis.

A detailed knowledge of a protein's functional site is an absolute prerequisite for understanding its mode of action at the molecular level. However, the rapid pace at which sequence and structural information is being accumulated for proteins greatly exceeds our ability to determine their biochemical roles experimentally. As a result, computational methods are required which allow for the efficient processing of the evolutionary information contained in this wealth of data, in particular that related to the nature and location of functionally important sites and residues. The method presented here, referred to as conserved functional group (CFG) analysis, relies on a simplified representation of the chemical groups found in amino acid side-chains to identify functional sites from a single protein structure and a number of its sequence homologues. We show that CFG analysis can fully or partially predict the location of functional sites in approximately 96% of the 470 cases tested and that, unlike other methods available, it is able to tolerate wide variations in sequence identity. In addition, we discuss its potential in a structural genomics context, where automation, scalability and efficiency are critical, and an increasing number of protein structures are determined with no prior knowledge of function. This is exemplified by our analysis of the hypothetical protein Ydde_Ecoli, whose structure was recently solved by members of the North East Structural Genomics consortium. Although the proposed active site for this protein needs to be validated experimentally, this example illustrates the scope of CFG analysis as a general tool for the identification of residues likely to play an important role in a protein's biochemical function. Thus, our method offers a convenient solution to rapidly and automatically process the vast amounts of data that are beginning to emerge from structural genomics projects.

Algorithms↗

PubMed2005

Exploration of the neural substrates of executive functioning by functional neuroimaging.

This review presents neuroimaging studies that have explored the cerebral substrates of executive functioning. These studies have demonstrated that different executive functions not only recruit various frontal areas but also depend upon posterior (mainly parietal) regions. These results are in accordance with the hypothesis that executive functioning relies on a distributed cerebral network that is not restricted to anterior cerebral areas. However, there exists an important heterogeneity in the cerebral areas associated with these different processes, and also between different tasks assessing the same process. Since these discrepant results could be due to the paradigms used (subtraction designs), recent results obtained with conjunction and interaction analyses are presented, which confirm the role of parietal areas in executive functioning and also demonstrate the existence of some specificity in the neural substrates of the executive processes of updating, shifting and inhibition. Finally, functional magnetic resonance imaging studies show that the activity in cerebral areas involved in executive tasks can be transient or sustained. Consequently, to better characterize the functional role of areas associated with executive functioning, it is important to take into account not only the localization of cerebral activity but also the temporal pattern of this activity.

Cerebral Cortex↗

PubMed2001

Cognitive neuropsychology and functional brain imaging: implications for functional and anatomical models of cognition.

We discuss the relations between functional imaging and cognitive neuropsychological research. We begin by elaborating on some of the problems of traditional neuropsychological research, which attempted to provide accounts of cognitive performance at a neural as well as at a functional level of description. The difficulties in making neural-level arguments from neuropsychological data include: problems of associated deficits, problems due to interactive effects between brain regions, problems with analyses based on behavioural syndromes, problems due to the influence of compensatory strategies, and problems in separating damaged from disconnected representations. We discuss how cognitive neuropsychology by-passed many of these problems by emphasising functional rather than neural-level theories, though problems with inferences at the neural-level remain. We then consider the contribution that functional imaging can make to cognitive neuropsychology. Using evidence drawn from studies of language, object recognition and visual attention, we argue that functional imaging complements cognitive neuropsychology by: (i) not being reliant on accidents of nature and by enabling effects of lesions on 'distant' neural areas to be measured, (ii) revealing the brain systems necessary and sufficient for a given task, (iii) providing tests of neural-level models of cognition, and by (iv) providing novel evidence on the mechanisms of functional recovery in patients. In addition to this, imaging studies can contribute directly to functional-level theories, by providing converging evidence on the neural locus of cognition--knowing 'where' can allow new inferences about 'how' a given task is performed.

Brain↗

PubMed2000

A functional diagnostic complexity index for rehabilitation medicine: measuring the influence of many diagnoses on functional independence and resource use.

OBJECTIVE: To develop an index that weights diagnostic information (International Classification of Diseases, 9th revision, Clinical Modification, or ICD-9-CM codes) by the extent to which it is expected to affect functional status and inpatient rehabilitation length of stay (LOS). DESIGN: Eleven nationally prominent physiatrists assigned ICD-9-CM codes to ordinal categories by expected effect on functional recovery. A resulting functional diagnostic complexity index score was calculated for each patient by combining the ranked values of each ICD-9-CM code in the discharge record. Analyses were stratified across the 20 rehabilitation impairment categories (RICs) of the Functional Independence Measure-Function Related Groups. DATA: Patients (182,254) discharged from 465 inpatient rehabilitation units in larger hospitals and free-standing rehabilitation hospitals in 1995. RESULTS: High degrees of diagnostic complexity were associated with low levels of functional independence at admission within each of 20 RICs (Spearman R = .06 to .25). Depending on RIC, patients in the highest (compared with the lowest) complexity category had up to a 35% increase in rehabilitation LOS after accounting for the primary medical reason for rehabilitation and severity of disabilities at admission. CONCLUSION: This prototype index of medical complexity offers a promising approach for analyzing the cumulative effects of diagnoses on patients' initial functional status and rehabilitation LOS.

Activities of Daily Living↗

PubMed1990

On the natural tendency to progressive loss of remaining kidney function in patients with impaired renal function.

Patients who lose more than 50% of their functioning renal mass are at risk to develop progressive deterioration of their remaining kidney function, even though the process that caused the original loss of kidney function may no longer be present. The glomerular capillary hyperperfusion, hypertension, and hyperfiltration that occur in the surviving nephrons may play an important role in the natural tendency for renal function to deteriorate. Nevertheless, recent studies suggest that these glomerular hemodynamic events may not be the final common pathway for the natural deterioration of renal function, as was once thought. With regard to the general management of patients with impaired renal function, recent evidence suggests that controlling systemic blood pressure, reducing dietary protein and phosphorus intake, and controlling hyperlipidemia may be effective in slowing the loss of renal function.

Hormones↗

PubMed2003

The perceived healthiness of functional foods. A conjoint study of Danish, Finnish and American consumers' perception of functional foods.

Functional foods presumably enable the consumer to lead a healthier life without changing eating habits. Whether consumers accept this proposition or not is potentially influenced by their perceptions of the healthiness of the processing methods, enrichment components, food-types, and health claims used in the production and marketing of functional foods. Because consumers may perceive functional enrichment as interfering with nature, cultural values pertaining to man's manipulation of nature may also influence consumer acceptance of functional foods. The purpose of the study described here is to clarify to which extent Danish, Finnish and American consumers' perceptions of the healthiness of functional foods are explained by the factors mentioned above. The general results indicate that values pertaining to man's manipulation of nature is only modestly related to the acceptance of functional foods, whereas the use of different health claims, processing methods, enrichments, product types, and especially the interactions between the two latter, are important determinants of consumers' perceptions of the healthiness of functional foods.

Consumer Behavior↗

PubMed1999

Neural network approximation of continuous functionals and continuous functions on compactifications.

This article characterizes the set of activation functions, bounded or unbounded, that allow feedforward network approximation of the continuous functions on the classic two-point compactification of R(1). The characterization fails when the set of targets are continuous functions on the classic compactifications of R(n), n>/=2. Nonpolynomial, analytic activation functions with input-to-hidden weights in very limited sets allow approximation of continuous function over compact sets in R(n), while even sigmoidal activation functions with weights in limited sets cannot approximate continuous functions on compactifications. The abstract structure foregrounded by compactification leads directly to possibility results for multi-layer networks and possibility results for neural networks in infinite dimensional settings.

Journal Article↗

PubMed2002

Functions of the stratum corneum in systemic sclerosis as distinct from hypertrophic scar and keloid functions.

Both transepidermal water loss (TEWL) and skin surface high-frequency conductance are functions of the skin barrier. Systemic sclerosis (SSc) and hypertrophic scar (HS)/keloid are characterized by abnormal fibrotic changes in the dermis. Since the close interrelationship between the epidermis and the dermis has been well established, we analyzed the stratum corneum functions of forearm skin in 39 SSc patients after assessing the degree of the skin thickening and compared those functions with 10 age-matched normal controls. We also analyzed the stratum corneum functions of HS or keloid lesions in seven patients using the same methods, and compared those functions to adjacent or contralateral normal skin in identical patients. Neither the TEWL, nor high-frequency conductance of forearm skin in SSc patients were significantly different from those in normal controls. There was no correlation between the levels of TEWL or high-frequency conductance and the degree of skin thickening in SSc. In HS or keloid conditions, high-frequency conductance was significantly elevated (42.5+/-8.9 vs. 26.4+/-5.7, P<0.001). Although TEWL was elevated, there was no statistical significance (48.6+/-39.7 vs. 25.1+/-10.1). Our results revealed that stratum corneum functions are distinct between SSc and HS or keloid. This may reflect the various natures of dermal changes, which in turn differentiate the functions of the stratum corneum in the diseases.

Adult↗

PubMed2001

Functional assessment of non-heart-beating donor lungs: prediction of post-transplant function.

OBJECTIVES: To enable an increase in the numbers of donor lungs using organs from non-heart-beating donors (NHBD). To develop an isolated ventilation and perfusion technique to assess the degree of warm ischaemic organ injury suffered prior to retrieval, thereby enabling identification of lungs with predictably good post-transplant function. METHODS: Lungs from Landrace-Yorkshire White cross pigs were retrieved after 1 (NHBD(1)), 2 (NHBD(2)) or 4 h (NHBD(4)) post-hypoxic death induced by cessation of ventilation. Control organs were retrieved using standard techniques for each group from matched animals immediately following aortic cross-clamping (Control(1) and combined Control(2,4)). Modified Euro-Collins pulmoplegia was used in all groups, prior to ventilating a single lung with 100% oxygen and perfusion with neutrophil-depleted and deoxygenated blood. For all of the lungs in the NHBD(2) and combined Control(2,4) groups, and one of the successfully perfused NHBD(4), the contralateral lung was then transplanted with post-transplant function assessed for 12 h. All animals were anaesthetized throughout and euthanased without regaining consciousness. RESULTS: On assessment, oxygenation after 5 min of perfusion did not differ between NHBD(1) (n=4) vs. Control(1) (n=5; analysis of variance (ANOVA), P=0.152). However, oxygenation had deteriorated significantly in the NHBD(2) group (n=6) vs. Control(2,4) (n=8; ANOVA, P<0.0005) and was significantly poorer than initial values after 8 min (unpaired t-test with Bonferroni correction, P<0.03). In NHBD(4) (n=6), four lungs failed assessment due to the development of gross pulmonary oedema, although the remaining pair functioned as well as Control(2,4). Post-transplantation, NHBD(2) (n=6) contralateral lungs showed significantly poorer overall oxygenation, (mean+/-SD, 46+/-22 kPa) when compared with Control(2,4) (n=6; 59+/-16 kPa; ANOVA, P=0.001), although oxygenation was satisfactory. The contralateral organ from one successfully perfused NHBD(4) lung functioned well post-transplantation. CONCLUSIONS: The significant deterioration in oxygenating performance seen during assessment after 2 h warm ischaemia and the idiosyncratic function after 4 h warm ischaemia indicates the importance of functional testing of NHBD lungs. The similar deterioration in oxygenating performance seen post-transplantation in the contralateral lungs suggests that this method detects functional warm ischaemic lung injury.

Animals↗

PubMed2000

Comparison of the Gross Motor Function Measure and Paediatric Evaluation of Disability Inventory in assessing motor function in children undergoing selective dorsal rhizotomy.

This study was designed to compare assessment with the functional outcome measures Gross Motor Function Measure (GMFM) and Pediatric Evaluation of Disability Inventory (PEDI) over time, in children with cerebral palsy (CP) undergoing selective dorsal rhizotomy combined with individualised physiotherapeutic interventions. Using the Gross Motor Function Classification System (GMFCS), 18 children with spastic diplegia were divided into two groups according to age-related severity of motor function impairment. Data were collected preoperatively, and at 6 and 12 months postoperatively. Both instruments were sensitive to changes in function over time in the series as a whole and in the group with milder impairment, although the PEDI detected significant changes earlier. In the group with more severe impairment, changes in function were detected only with the PEDI, not with the GMFM. Thus, the instruments are to be considered complementary tests, because they measure different aspects of function.

Activities of Daily Living↗

PubMed1998

Empirical scoring functions. II. The testing of an empirical scoring function for the prediction of ligand-receptor binding affinities and the use of Bayesian regression to improve the quality of the model.

This paper tests the performance of a simple empirical scoring function on a set of candidate designs produced by a de novo design package. The scoring function calculates approximate ligand-receptor binding affinities given a putative binding geometry. To our knowledge this is the first substantial test of an empirical scoring function of this type on a set of molecular designs which were then subsequently synthesised and assayed. The performance illustrates that the methods used to construct the scoring function and the reliance on plausible, yet potentially false, binding modes can lead to significant over-prediction of binding affinity in bad cases. This is anticipated on theoretical grounds and provides caveats on the reliance which can be placed when using the scoring function as a screen in the choice of molecular designs. To improve the predictability of the scoring function and to understand experimental results, it is important to perform subsequent Quantitative Structure-Activity Relationship (QSAR) studies. In this paper, Bayesian regression is performed to improve the predictability of the scoring function in the light of the assay results. Bayesian regression provides a rigorous mathematical framework for the incorporation of prior information, in this case information from the original training set, into a regression on the assay results of the candidate molecular designs. The results indicate that Bayesian regression is a useful and practical technique when relevant prior knowledge is available and that the constraints embodied in the prior information can be used to improve the robustness and accuracy of regression models. We believe this to be the first application of Bayesian regression to QSAR analysis in chemistry.

Bayes Theorem↗

PubMed2002

Loss-of-function variants of the human melanocortin-1 receptor gene in melanoma cells define structural determinants of receptor function.

The alpha-melanocyte-stimulating hormone (alphaMSH) receptor (MC1R) is a major determinant of mammalian skin and hair pigmentation. Binding of alphaMSH to MC1R in human melanocytes stimulates cell proliferation and synthesis of photoprotective eumelanin pigments. Certain MC1R alleles have been associated with increased risk of melanoma. This can be theoretically considered on two grounds. First, gain-of-function mutations may stimulate proliferation, thus promoting dysplastic lesions. Second, and opposite, loss-of-function mutations may decrease eumelanin contents, and impair protection against the carcinogenic effects of UV light, thus predisposing to skin cancers. To test these possibilities, we sequenced the MC1R gene from seven human melanoma cell (HMC) lines and three giant congenital nevus cell (GCNC) cultures. Four HMC lines and two GCNC cultures contained MC1R allelic variants. These were the known loss-of-function Arg142His and Arg151Cys alleles and a new variant, Leu93Arg. Moreover, impaired response to a superpotent alphaMSH analog was demonstrated for the cell line carrying the Leu93Arg allele and for a HMC line homozygous for wild-type MC1R. Functional analysis in heterologous cells stably or transiently expressing this variant demonstrated that Leu93Arg is a loss-of-function mutation abolishing agonist binding. These results, together with site-directed mutagenesis of the vicinal Glu94, demonstrate that the MC1R second transmembrane fragment is critical for agonist binding and maintenance of a resting conformation, whereas the second intracellular loop is essential for coupling to the cAMP system. Therefore, loss-of-function, but not activating MC1R mutations are common in HMC. Their study provides important clues to understand MC1R structure-function relationships.

Alleles↗

PubMed2001

Medium-term functional benefits in children with cerebral palsy treated with botulinum toxin type A: 1-year follow-up using gross motor function measure.

One of the main goals when treating spasticity is to relieve pain and improve function. Intramuscular injection of botulinum toxin type A (BTX-A) has gained widespread acceptance in the treatment of spastic cerebral palsy. Several studies have clearly shown the short-term functional benefit of BTX-A treatment. Information is limited, however, on the efficacy of medium and long-term regimens, using repeated injection of BTX-A. The aim of the present open-label, prospective study was to evaluate functional outcome in children with spastic cerebral palsy after 1 year of treatment with BTX-A, using the Gross Motor Function Measure (GMFM) as a validated outcome measure. Patients (n=25, age 1.5--15.5 years) were treated with BTX-A for adductor spasm (n=12) or pes equinus (n=13). The local effect was evaluated using passive range of motion and modified Ashworth Scale. Apart from a significant improvement in joint mobility and reduction of spasticity compared to pretreatment values (P < 0.01), we demonstrated a significant improvement of gross motor function after 12 months of treatment, with a median gain of 6% in total and goal scores (P < 0.001). An increase in GMFM scores was particularly evident in younger and moderately impaired children (Gross Motor Function Classification System level III). Whether the observed improvement in gross motor function in children with cerebral palsy is specifically related to therapy with BTX-A or represents at least in part the natural course of motor development still needs clarification.

Adolescent↗

PubMed2000

Comparison of the Framingham risk function-based coronary chart with risk function from an Italian population study.

AIMS: The aim is to compare the coronary risk chart published by the European Task Force for Prevention of Coronary Heart Disease and produced using a Framingham risk function, with a risk function derived from an Italian population study. METHODS AND RESULTS: Coronary risk function in this study was the result of longitudinal experience in an Italian middle-aged population of 1656 male subjects followed-up for 25 years. To comply with the Framingham equation the same risk factors (age, systolic blood pressure, total serum cholesterol and smoking habits), end-points (any possible coronary event including angina pectoris), and length of follow-up (10 years) were used, and the model (log-linear accelerated time failure model, accommodating the Weibull distribution) was similar. Comparisons were made computing the coronary risk for each cell of the coronary risk chart for men aged 40, 50 and 60 years. The Italian risk function produced highly significant coefficients for all four risk factors. Forty-four out of a total of 120 cells had a coronary risk of 20% or more in 10 years following the coronary risk chart, whereas this was reduced to four while using the Italian risk function (P<0.001). The Italian risk function largely underestimated the corresponding levels produced by the coronary risk chart and vice versa. CONCLUSION: The Framingham risk function-based coronary risk chart overestimates absolute coronary risk in countries characterized by a lower incidence of coronary events and should be used with caution.

Adult↗

PubMed2004

Efficient hybrid density functional calculations in solids: assessment of the Heyd-Scuseria-Ernzerhof screened Coulomb hybrid functional.

The present work introduces an efficient screening technique to take advantage of the fast spatial decay of the short range Hartree-Fock (HF) exchange used in the Heyd-Scuseria-Ernzerhof (HSE) screened Coulomb hybrid density functional. The screened HF exchange decay properties and screening efficiency are compared with traditional hybrid functional calculations on solids. The HSE functional is then assessed using 21 metallic, semiconducting, and insulating solids. The examined properties include lattice constants, bulk moduli, and band gaps. The results obtained with HSE exhibit significantly smaller errors than pure density functional theory (DFT) calculations. For structural properties, the errors produced by HSE are up to 50% smaller than the errors of the local density approximation, PBE, and TPSS functionals used for comparison. When predicting band gaps of semiconductors, we found smaller errors with HSE, resulting in a mean absolute error of 0.2 eV (1.3 eV error for all pure DFT functionals). In addition, we present timing results which show the computational time requirements of HSE to be only a factor of 2-4 higher than pure DFT functionals. These results make HSE an attractive choice for calculations of all types of solids.

Journal Article↗