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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↗

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↗

PubMed2000

Novel gain-of-function mutations of platelet glycoprotein IBalpha by valine mutagenesis in the Cys209-Cys248 disulfide loop. Functional analysis under statis and dynamic conditions.

Platelet-type von Willebrand disease is a bleeding disorder resulting from gain-of-function mutations of glycoprotein (GP) Ibalpha that increase its affinity for von Willebrand factor (vWf). The two known naturally occurring mutations, G233V and M239V, both enrich the valine content of an already valine-rich region within the Cys(209)-Cys(248) disulfide loop. We tested the effect of converting other non-valine residues in this region to valine. Of 10 mutants expressed in CHO cells as components of GP Ib-IX complexes, four displayed a gain-of-function phenotype (G233V, D235V, K237V, and M239V) based on (125)I-vWf binding and adhesion to immobilized vWf. The remainder displayed loss-of-function phenotypes. The gain-of-function mutants bound vWf spontaneously and had a heightened response to low concentrations of ristocetin or botrocetin, whereas the loss-of-function mutants bound vWf more poorly than wild-type GP Ibalpha. No distinct gain- or loss-of-function conformations were identified with conformation-sensitive antibodies. Compared with cells expressing wild-type GP Ibalpha, cells expressing the gain-of-function mutants rolled significantly more slowly over immobilized vWf under flow than wild-type cells and were able to adhere to vWf coated at lower densities. In aggregate, these data indicate that the region of GP Ibalpha bounded by Asn(226) and Ala(244) regulates the affinity for vWf.

Amino Acid Sequence↗

PubMed1972

Studies on thymus function. 3. Duration of thymic function.

The immune functions of neonatally thymectomized C3Hf mice exposed only temporarily to thymus function show a progressive decay with time in the absence of the thymus. The immune responses studied at different ages in the range of 100-600 days were: first-set rejection of H-2-compatible and incompatible skin allografts, second-set rejection of skin allografts, capacity of spleen cells to produce graft-versus-host reactions in F(1) hybrids, resistance to infection with mouse hepatitis virus, and response of spleen cells to phytohemagglutinin in vitro. These long-term studies had the purpose of determining the duration of the restoration induced by thymus function when the mice were exposed only temporarily to it. Different models were used but the two basic ones were: (a) mice grafted intraperitoneally at 15 days of age with a syngeneic thymus that was removed surgically at 10, 20, or 30 days after grafting, and (b) mice grafted at 15 days of age with allogeneic strain A thymoma or C57BL thymus, these representing situations in which there is spontaneous rejection of the restoring graft. In all the experimental models used, the animals were restored when tested at 100 days of age, but progressively became immunologically incapacitated at 200-300 days of age. From the more controlled experiments in which the restoring thymus graft was removed surgically, the following conclusions can be drawn. (a) A short exposure to a thymus graft can produce restoration of immune functions in neonatally thymectomized mice, but this restoration is not self-sustaining in the absence of the thymus and declines progressively with age. The decline usually starts at 200-300 days of age. (b) This was especially clear in experiments in which the same animal was tested twice in its lifetime for capacity to produce graft-versus-host reactions; these animals were competent at 100 days and became incompetent at 400 days of age. (c) The shortest period of thymic exposure studied was 10 days; if vascularization of the graft is taken into account, 2-3 days of thymic function are sufficient to produce restoration. (d) The immune decay observed in the thymectomized animals exposed temporarily to thymus was more profound than the physiological decay of immunity observed in control animals of similar age. (e) Of all the tests studied, the response of spleen cells to phytohemagglutinin was to be preserved the longest in animals exposed only temporarily to thymic function. The present results were interpreted in accordance with our previous findings indicating that a population of postthymic cells can be developed by temporary exposure of neonatally thymectomized animals to thymic function, but that this population is not self-sustaining in the absence of thymus and progressively decays by physiological attrition.

Age Factors↗

PubMed1997

Functional dose-volume histograms for functionally heterogeneous normal organs.

Functional dose-volume histograms are proposed as an extension of the conventional dose-volume histograms, for quantitative assessment of three-dimensional radiation dose coverage of functionally heterogeneous normal organs. Examples are given to illustrate possible applications of this approach to the treatment of a brain tumour or a lung tumour, in which cases the distribution of the normal organ function can be obtained from functional dose-volume modalities. It is shown that a significant difference exists between the functional dose-volume histograms and the conventional dose-volume histograms when the normal organ function is non-uniformly distributed within the organ. Utilization of functional dose-volume histograms as the input for the calculation of normal tissue complication probabilities is discussed for different normal tissue structures.

Humans↗

PubMed1990

Cloning and molecular characterization of a metabolic gene with development functions in Drosophila. I. Analysis of the head function of Punch.

In an effort to understand the functions of pterins throughout development we have been studying Punch (Pu), the structural gene for the enzyme GTP cyclohydrolase in Drosophila melanogaster. This enzyme catalyzes the first step in the pterin biosynthetic pathway. The Pu gene product is required for vital functions at two distinct stages in embryogenesis, and a pigmentation function in the eye of the young adult. We have localized the Pu region to 29 kb of DNA through the analysis of lesions present in Pu mutants. Since all of the mutations that were mapped affect the eye pigmentation function of Pu, and since this function is the best defined biochemically, we have concentrated on identifying and characterizing Pu products required for eye pigmentation in our initial examination of the cloned region. Four different transcripts from this region are expressed in the adult head. We show that one of these transcripts, the 1.7-kb species, is responsible for the pigmentation function through the analysis of mutant transcripts and the use of an in vitro translation assay. A 2-kb region lying within the locus is specifically required for this eye pigmentation function.

Animals↗

PubMed2001

Functional divergence in the caspase gene family and altered functional constraints: statistical analysis and prediction.

In this article, we explore the pattern of type I functional divergence (i.e., altered functional constraints or site-specific rate difference) in the caspase gene family that is important for apoptosis (programmed cell death) and cytokine maturation. By taking advantage of substantial experimental data from caspases, the functional/structural basis of our posterior predictions from sequence analysis was extensively studied. Our results are as follows: (1) Phylogenetic analysis shows that the evolution of major caspase-mediated pathways has been facilitated by gene duplications, (2) type I functional divergence (altered functional constraints) is statistically significant between two major subfamilies, CED-3 and ICE, (3) 4 of 21 predicted amino acid residues (for site-specific rate difference between CED-3 and ICE) have been verified by experimental evidence, and (4) we found that some CED-3 caspases may inherit more ancestral functions, whereas other members may employ some recently derived functions. Our approach can be cost effective in functional genomics to make statistically sound predictions from amino acid sequences.

Amino Acid Sequence↗

PubMed2001

Measuring higher level physical function in well-functioning older adults: expanding familiar approaches in the Health ABC study.

BACKGROUND: To evaluate development and progression of functional limitation and retain comparability with established approaches, we raised the measurement ceiling of commonly used self-report and performance-based measures of function. This study evaluated the utility and concurrent validity of these expanded measures. METHODS: The study population consisted of 3075 black and white men and women aged 70 to 79 years, with no reported mobility limitations or disability, participating in the Health, Aging, and Body Composition, or Health ABC study. Self-report measures were expanded by ascertaining ease of performance and including more demanding levels of some tasks. A single foot stand and narrow walk supplemented an established performance battery. For walking endurance, we developed the Long Distance Corridor Walk (LDCW), which includes distance covered in 2 minutes and the time to walk 400 m. RESULTS: The expanded self-report items identified one half of the men and one third of the women as exceptionally well functioning and 10% to 13% of men and 21% to 36% of women with lower capacity. The supplemented and rescored performance battery discriminated function over the full range. The LDCW further differentiated walking capacity at the high end and also identified a subgroup with limitations. The self-report and performance measures were significantly, but weakly, correlated (0.13-0.35) and were independent predictors of walking endurance. CONCLUSIONS: Well-functioning persons in their 70s exhibit a broad range of functional capacity readily ascertained by expanded self-report and performance tests. Significant associations among these measures support their concurrent validity, but generally weak correlations indicate they tap different, but important, dimensions of physical function.

Aged↗

PubMed1998

Rodent Y chromosome TSPY gene is functional in rat and non-functional in mouse.

Recombination is believed to prevent genetic deterioration in sexual populations because it allows conservation of functional genotypes by removing deleterious mutations. Moreover, evidence that non-recombining segments of a genome deteriorate is provided by genetic experiments in Drosophila and yeast. Y chromosomes generally do not recombine along most of their length, and thus Y chromosome genes, despite having been selectively maintained for their function, could be lost from the genome. Here we present definitive evidence that functional Y genes can be lost from the mammalian genome. TSPY genes must have been selectively maintained on the mammalian Y chromosome since before the radiation of eutheria, 80 million years ago, as they are found conserved on the Y chromosome in two mammalian orders: primate and artiodactyl. We have now identified TSPY on the rodent Y chromosome, in mouse and rat. The gene structure and expression of rat TSPY suggest that it is a functional, testis-specific gene, but the closely related mouse gene, Tspy, has clearly become non-functional, producing only low levels of aberrantly spliced transcripts. Thus TSPY lost its function in the mouse lineage after its divergence from the rat lineage. So, in the case of Tspy at least, the absence of recombination does appear to have led to the loss of a functional gene.

Animals↗

PubMed1992

Changes in hand function in the aging adult as determined by the Jebsen Test of Hand Function.

The Jebsen Test of Hand Function is used to assess a broad range of hand functions required for activities of daily living. The time needed to complete a variety of subtests is measured, with high scores indicative of abnormality. Normative values have been established for men and women in two age groups: 20 to 59 years and 60 to 94 years. The purpose of this study was to determine whether hand function, as measured by the Jebsen test, declines with age in subjects over the age of 60 years. A total of 121 men and women were given the test and grouped into the following age categories: (1) 60 to 69 years, (2) 70 to 79 years, and (3) 80 to 89 years. Hand function decreased with age in both men and women. There were significant positive correlations between age and time needed to complete the various subtests, and analyses of variance revealed significant differences between subjects in their 80s and those in their 60s and 70s. In only a few tasks were there significant differences between men and women within any age group. Because of the decrease in normal function with age, measurements obtained with the Jebsen test in the elderly should be compared with normative values that are obtained from similarly aged subjects. [Hackel ME, Wolfe GA, Bang SM, Canfield JS. Changes in hand function in the aging adult as determined by the Jebsen Test of Hand Function.

Aged↗