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PubMed2002

Estimation of age-specific reference intervals for skewed data.

OBJECTIVES: To compare Cole's LMS method with Wright and Royston's Exponential-Normal (EN) method for estimating reference intervals and generating smooth centile curves for the body mass index (weight in kg/height in meters squared) measurements of children aged 6 to 13 years. METHODS: In the LMS method, the parameters L (the power needed to normalize the data), M (median) and S (coefficient of variation) are modeled as smoothed fits of maximum likelihood estimates. In the Exponential-Normal method, the three parameters mean, standard deviation and skewness are estimated separately using multiple regression techniques. RESULTS: The centiles generated by the LMS and EN methods are close in most of the age groups. The 2.5th and 97.5th quantiles of the interval of the differences between the loss function scores of the LMS and EN methods calculated by bootstrap was found to include zero, indicating that the difference in loss function scores of the two methods is random and not systematic. CONCLUSIONS: The two methods are simple to use and generate comparable centile curves.

Adolescent↗

PubMed2005

Self-reported visual function in healthy older people in Britain: an exploratory study of associations with age, sex, depression, education and income.

BACKGROUND: Tractable but undetected visual impairment in older people may be relatively common, particularly amongst the very old and in more deprived populations. Measurement of visual acuity is unlikely to be helpful in identifying this impairment, but targeted assessment of visual function may be beneficial. There is uncertainty about the defining characteristics of the target group. OBJECTIVE: To explore factors associated with self-reported visual impairment in community dwelling older people. METHODS DESIGN: secondary cross sectional analysis of baseline data from a randomised controlled trial. SETTING: three large group practices in outer London. PARTICIPANTS: older people aged 65 and over enrolled in a study of health risk appraisal. METHOD: postal questionnaire using questions from the National Eye Institute Visual Function questionnaire. RESULTS: Moderate or extreme visual function loss occurred in 4 to 12% of community-dwelling older people in this population reporting less than excellent vision, depending on which aspect of visual function is considered. Visual function loss in this subgroup increases in prevalence with advancing age, but is not associated with female sex, low educational attainment or low income. It is associated with depressed mood. CONCLUSION: Questions about visual function identify a group of older people whose vision and mental state needs further investigation.

Aged↗

PubMed2001

Working with low back pain: problem-solving orientation and function.

A number of ergonomic, workplace and individual psychosocial factors and health behaviors have been associated with the onset, exacerbation and/or maintenance of low back pain (LBP). The functional impact of these factors may be influenced by how a worker approaches problems in general. The present study was conducted to determine whether problem-solving orientation was associated with physical and mental health outcomes in fully employed workers (soldiers) reporting a history of LBP in the past year. The sample consisted of 475 soldiers (446 male, 29 female; mean age 24.5 years) who worked in jobs identified as high risk for LBP-related disability and reported LBP symptoms in the past 12 months. The Social Problem-Solving Inventory and the Standard Form-12 (SF-12) were completed by all subjects. Hierarchical multiple regression analyses were used to predict the SF-12 physical health summary scale from interactions of LBP symptoms with each of five problem-solving subscales. Low scores on positive problem-solving orientation (F(1,457)=4.49), and high scores on impulsivity/carelessness (F(1,457)=9.11) were associated with a steeper gradient in functional loss related to LBP. Among those with a longer history of low-grade LBP, an avoidant approach to problem-solving was also associated with a steeper gradient of functional loss (three-way interaction; F(1,458)=4.58). These results suggest that the prolonged impact of LBP on daily function may be reduced by assisting affected workers to conceptualize LBP as a problem that can be overcome and using strategies that promote taking an active role in reducing risks for LBP. Secondary prevention efforts may be improved by addressing these factors.

Adult↗

PubMed2000

The evolution of staminodes in angiosperms: patterns of stamen reduction, loss, and functional re-invention.

Stamens that have lost their primary function of pollen production, or staminodes, occur uncommonly within angiosperms, but frequently fulfill important secondary floral functions. The phylogenetic distribution of staminodes suggests that they typically arise during evolutionary reduction of the androecium. Differences in the genetic control and patterns of stamen loss between actinomorphic and zygomorphic flowers shape staminode development. In clades with actinomorphic flowers, staminodes generally replace an entire stamen whorl and staminode loss seems irreversible. In contrast, in clades with zygomorphic flowers staminodes evolve from a subset of the stamens in a whorl and staminodes can reappear in a lineage after being lost (e.g., Cheloneae, Scrophulariaceae). If staminodes do not adopt new functions during androecium reduction they are lost quickly, so that nonfunctional staminodes appear only in recently derived taxa. Alternatively, when staminodes assume new floral roles, either directly or indirectly after a nonfunctional period, they can become integral floral components which perpetuate within clades (e.g., Orchidaceae). Indirect evolution of staminode function allows greater flexibility of function by allowing staminodes to take over roles not performed by stamens, such as involvement in mechanisms to prevent self-pollination and mechanisms of explosive pollination. Multifunctional staminodes characterize lineages with universal or widespread staminodes.

Journal Article↗

PubMed1996

The relationship between age, gender and psychological distress in rehabilitation inpatients.

Although commonly accepted as the dominant emotional reaction to functional loss, the reported occurrence of depression in rehabilitation patients varies widely. Rather than focusing solely on depressive symptoms, this study furthers our understanding of emotional distress following a functional loss by assessing a range of psychiatric symptoms. A series of rehabilitation patients admitted to an urban hospital inpatient unit is used as the sample (n = 48). Demographic, neuropsychological, and a functional independence measure were included as independent variables. The statistical analysis revealed that-although age was not correlated with years of education, functional status, or neuropsychological impairment-there was a significant inverse relationship between age and reported emotional distress. Utilizing MANCOVA to explore the impact of age and gender on specific groups of psychiatric symptoms revealed that both younger and male patients tended to express psychiatric symptoms more frequently. The importance of considering age and gender in evaluation of emotional distress in rehabilitation is supported in this comprehensive study of psychiatric symptoms.

Adaptation, Psychological↗

PubMed1991

Tendon transfers in traumatic foot.

A clinical review was performed of 11 cases of traumatic foot treated by tendon transfer. Among 11 patients, there were eight males and three females, ranging from four to 36 years of age. The anterior tibial tendon was used in six cases for tendon transfer and among these, split anterior tibial tendon was used in three cases in children. The posterior tibial tenodn was used in two cases and the extensor digitorum longus tendon of the foot was in three cases. In six cases of soft tissue injury where tendon transfer was impossible, microvascular free cutaneous flap transplantation was combined with the tendon transfer. Follow-up results were obtained from 25 months to nine years. Excellent results were obtained in eight cases and satisfactory results in three cases. For the correction of function loss in traumatic foot, tendon transfere were a useful method for the recovery of active motion of the foot. For the restoration of function loss in the traumatic foot, there are several methods of treatment such as tendon transfer, arthrodesis and tenodesis, but for recovery of the active motion of the foot, tendon transer is the only useful method.

Adolescent↗

PubMed1993

Accuracy of the 1990 census and undercount adjustments.

"In July 1991 the [U.S.] Census Bureau recommended to its parent agency, the Department of Commerce, that the 1990 census be adjusted for undercount. The Secretary of Commerce decided not to adjust, however. Those decisions relied at least partly on the Census Bureau's analyses of the accuracy of the census and of the proposed undercount adjustments based on the Post-Enumeration Survey (PES).... This article describes the total error analysis and loss function analysis of the Census Bureau. In its decision not to adjust the census, the Department of Commerce cited different criteria than aggregate loss functions. Those criteria are identified and discussed."

Americas↗

PubMed1998

Estrogen-induced rat pituitary tumor is associated with loss of retinoblastoma susceptibility gene product.

Chronic treatment of rats with the estrogens 17beta-estradiol or diethylstilbestrol (DES) induces pituitary tumors in Fischer 344 but not Brown-Norway or Sprague-Dawley rats. Functional loss of retinoblastoma susceptibility gene product (pRb), a major regulatory protein for the G1 to S transition of the cell cycle, has been shown in several tumors. Here we report a decreased level of pRb in pituitary tumors of the Fischer 344 rat as compared with resistant Sprague Dawley and Brown-Norway strains. pRb protein levels decreased 70% in Fischer 344 rats that were treated with diethylstilbestrol for 10 weeks as compared with tumor resistant control animals. Interestingly, the F1 hybrid (Fischer 344 x Norway) showed an intermediate range of pRb protein expression as compared with those of the parental strains. pRb expression levels in nonhemorrhagic F2 (F1 x F1) rats correlated with the size of the tumors. One week withdrawal of DES increased pRb levels as compared with continuously treated rats. Also, there was a decreased association of cyclin D and cyclin dependent kinase in susceptible tumors, supporting the hypothesis of a physical and possibly functional loss of pRb in the diethylstilbestrol-induced pituitary tumor. These results suggest that the difference in pRb regulation, whether it is a direct or indirect effect of estrogen, is related to tumor resistance or susceptibility in these two rat strains.

Animals↗

PubMed2006

The growth compromised HSV-2 mutant DeltaRR prevents kainic acid-induced apoptosis and loss of function in organotypic hippocampal cultures.

We have previously shown that the HSV-2 anti-apoptotic protein ICP10PK is delivered by the replication incompetent virus mutant DeltaRR and prevents kainic acid (KA)-induced epileptiform seizures and neuronal cell loss in the mouse and rat models of temporal lobe epilepsy. The present studies used DeltaRR and the ICP10PK deleted virus mutant DeltaPK to examine the mechanism of neuroprotection. DeltaRR-infected neuronal cells expressed a chimeric protein in which ICP10PK is fused in frame to LacZ (p175) while retaining ICP10PK kinase activity. DeltaPK-infected neuronal cells expressed a mutant ICP10 protein that is deleted in the PK domain and is kinase negative (p95). p175 and p95 were expressed in CA3 (86+/-3%) and CA1 (69+/-7%) cells from DeltaRR or DeltaPK-infected organotypic hippocampal cultures (OHC) and 80-85% of the ICP10 positive cells co-stained with antibody to beta(III) Tubulin (neuronal marker). DeltaRR, but not DeltaPK, inhibited KA-induced cell death and caspase-3 activation in CA3 neurons, an inhibition seen whether DeltaRR was delivered 2 days before or 2 days after KA administration (95% neuroprotection). Neuroprotection was associated with ERK and Akt activation and was abrogated by simultaneous treatment with the MEK (U0126) and PI3-K (LY294002) inhibitors. DeltaRR-mediated neuroprotection was associated with increased expression of the anti-apoptotic protein Bag-1 and decreased expression of the pro-apoptotic protein Bad. The surviving neurons retained normal synaptic function potentially related to increased expression of the transcription factor CREB. The data indicate that DeltaRR is a promising platform for neuroprotection from excitotoxic injury.

Animals↗

PubMed1978

Visual field defects, cup-disc ratio and fluorescein angiography in glaucomatous optic atrophy.

Fluorescein angiography was carried out in 150 glaucoma subjects. Among them 94 subjects were selected to evaluate the correlation between functional loss and the findings of fluorescein angiography in the optic disc. The intensity of fluorescence was assessed in the superficial reticular capillaries and radial epipapillary capillaries. Functional loss was estimated by the visual field defects and cup-disc ratio. A marked decrease in the capillaries was seen in accordance with the increase in the cup-disc ratio. Also, the intensity of fluorescence in the optic disc paralleled the change in the visual field: the greater the deterioration in the visual field, the fewer the capillaries in the optic nerve head and vice versa. The fluorograms of 94 subjects were placed in one out of six groups, i.e. (1) normal, (2) arcuate scotoma, (3) superior or inferior nasal defects, (4) superior or inferior defects, (5) central residue or (6) temporal residue. The common factors correlating the fluorescein angiography in the glaucomatous optic disc with visual field loss were explored in 94 subjects, and it was possible to predict the visual field change from the capillary distribution in the glaucomatous optic disc.

Fluorescein Angiography↗

PubMed1993

Aprotinin in pediatric cardiac operations: platelet function, blood loss, and use of homologous blood.

Excessive hemorrhage secondary to cardiopulmonary bypass may be encountered after pediatric cardiac operations. Platelet dysfunction appears to be especially responsible for this problem. The proteinase inhibitor aprotinin is suggested to possess platelet preservation properties and reduce blood loss in this situation. The effects of aprotinin (25,000 U/kg after induction of anesthesia, 25,000 U/kg added to the prime, 25,000 U/kg every hour of cardiopulmonary bypass) on platelet function were randomly studied in 12 children with a weight of less than 10 kg (group 2) and 12 children weighing more than 10 kg (group 4), who were compared with two groups of children without aprotinin (group 1, < 10 kg; group 3, > 10 kg). Twelve children undergoing major vessel operations without cardiopulmonary bypass and aprotinin served as a control. Platelet function was assessed using aggregometry (turbidometric technique with adenosine diphosphate, 2.0 mumol/L; collagen, 4 micrograms/mL; epinephrine, 25 mumol/L; NaCl [control]). Platelet function was not altered in the control patients within the entire investigation period. Maximum aggregation in the small children was already lower at baseline in comparison with that of the children > 10 kg. Cardiopulmonary bypass was followed by a significant reduction in platelet aggregation in all groups. Treatment with aprotinin did not improve platelet function (maximum aggregation and maximum gradient of aggregation) in any group. On the first postoperative day, maximum aggregation in the small children exceeded baseline values, whereas in both groups of children > 10 kg baseline values had almost been established. Postoperative blood loss was not reduced by treatment with aprotinin.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗

PubMed2006

Ideal spatial radiotherapy dose distributions subject to positional uncertainties.

In radiotherapy a common method used to compensate for patient setup error and organ motion is to enlarge the clinical target volume (CTV) by a 'margin' to produce a 'planning target volume' (PTV). Using weighted power loss functions as a measure of performance for a treatment plan, a simple method can be developed to calculate the ideal spatial dose distribution (one that minimizes expected loss) when there is uncertainty. The spatial dose distribution is assumed to be invariant to the displacement of the internal structures and the whole patient. The results provide qualitative insights into the suitability of using a margin at all, and (if one is to be used) how to select a 'good' margin size. The common practice of raising the power parameters in the treatment loss function, in order to enforce target dose requirements, is shown to be potentially counter-productive. These results offer insights into desirable dose distributions and could be used, in conjunction with well-established inverse radiotherapy planning techniques, to produce dose distributions that are robust against uncertainties.

Algorithms↗

PubMed1999

Comparative analysis of motoneuron loss and functional deficits in PMN mice: implications for human motoneuron disease.

We have investigated the correlation between functional and morphological deficits in PMN mice, an animal model of human motoneuron disease. Electrophysiologic investigations showed first abnormalities, i.e. reduction of M-response amplitudes, already at postnatal d 13 when the disease was not yet phenotypically apparent, and when motoneuron and motor axon numbers were still normal. After d 27, a loss of more than 30% of motoneuron axons and cell bodies was detectable in the phrenic nerve and facial nucleus, respectively. At that stage, PMN mice showed severe functional and electrophysiological deficits. At later stages of the disease when still more than 50% of motor axons and at least 60% of motoneuron cell bodies were present, the distal compound muscle action potential amplitude decreased by more than 95% in small foot muscles after sciatic nerve stimulation. We conclude that functional deficits precede structural deficits in this animal model of human motoneuron disease. Our findings are in agreement with the concept of the 'sick motoneuron' in this animal model of motoneuron disease rather than the idea of progressive loss of motoneurons resulting in disease only after a significant number of motoneurons has degenerated.

Action Potentials↗

PubMed2005

A novel loss-of-function deletion in sodium/iodide symporter gene in follicular thyroid adenoma.

The sodium/iodide symporter (NIS) actively transports iodide into thyrocytes. However, in thyroid carcinoma, down-regulated or mis-targeted NIS expression is commonly found and usually correlates with tumor dedifferentiation and loss of radioiodine uptake capacity. In this study, we screened NIS genes of thyroid tumor tissues from three patients with thyroid carcinoma by using reverse transcription-polymerase chain reaction and nucleotide sequencing. We found a novel exon 6 deletion in NIS gene. We then examined the NIS gene from the blood of this patient. The nucleotide sequences of the flanking region of exon 6 were normal. By transient transfection and I-125 uptake assay, we found that the wild type NIS-expressing HepG2 cells accumulated six times more iodide than mutant and mock HepG2 cells. Our data demonstrated that the exon 6 deletion causes an iodide-trapping defect.

Adenoma↗

PubMed1995

Synergy between a human c-myc transgene and p53 null genotype in murine thymic lymphomas: contrasting effects of homozygous and heterozygous p53 loss.

Activation of the c-myc oncogene and functional loss of the p53 tumour suppressor gene are among the most frequently recorded genetic lesions in neoplasia but their combined effect has not previously been investigated. By breeding together mice transgenic for human c-myc (CD2-myc) and mice carrying an inactive p53 allele (p53-/-) we found that these genetic lesions act synergistically in vivo. Offspring carrying the CD2-myc transgene and the homozygous p53 null mutation (p53-/-/CD2-myc) were viable but developed thymic lymphomas with dramatically increased frequency and reduced latency compared to both parental groups. The tumour phenotype was similar to that previously recorded for CD2-myc mice (predominantly CD3+, CD4+8+) but tumour clonal complexity and metastasis was significantly greater in the p53-/-/CD2-myc mice. In contrast, no significant increase in tumour incidence was seen in p53+/-/CD2-myc vs p53+/+/CD2-myc mice over a 6 month observation period. However, the loss of wild type p53 in a proportion of tumour cells in p53+/-/CD2-myc lymphomas suggests that wild type allele loss can occur as a late progression step rather than an initiating step in these tumours. We suggest that p53 loss of function may collaborate with the CD2-myc transgene at more than one stage in thymic lymphoma development.

Animals↗

PubMed1999

Complete loss of functional smooth muscle cells precedes vascular remodeling in rat aorta allografts.

BACKGROUND: The functional consequences of vascular remodeling in rat aorta allografts were studied at different times after transplantation (Tx). METHODS: At days 1, 3, 7, 14, 28, and 56 after Tx, rat aorta allografts (Dark Agouti [DA]-to-Lewis) were mounted as isolated organs, and their contractile properties tested with phenylephrine, KCl, or endothelin-1. Controls were native DA-aortae and DA-syngeneic grafts. Changes in alpha smooth muscle actin and morphology were assessed by immunoblotting and histology. RESULTS: PostTx syngeneic grafts presented similar functional and morphological properties to native aortae. In allografts, no morphological changes was detected at day 7 after Tx, but phenylephrine-induced vasoconstriction was reduced by 60%. Signs of medial smooth muscle cell (SMC) loss and adventitial inflammation were observed at day 14 after Tx, without neointima formation. A complete loss of contractile property was observed at day 28 after Tx in association with a 75% decrease in alpha-SMC actin, severe adventitial inflammation, and reduced medial cellularity. At this time, neointima was restricted to both edges of allografts. At day 56 after Tx, allografts were also not functional and exhibited neointima on their entire length. All these changes were prevented by treating recipients with cyclosporine (7.5 mg/kg/day). CONCLUSION: These results indicate that, after Tx, the contractile property of rat aorta allografts is altered before manifest vascular remodeling. Because this can be prevented by cyclosporine, it most likely reflects an acute rejection of SMC. These results also show that vascular graft dysfunction can be used to monitor the development of rejection in the rat aorta allograft model.

Actins↗

PubMed1991

Hepatitis B virus integration event in human chromosome 17p near the p53 gene identifies the region of the chromosome commonly deleted in virus-positive hepatocellular carcinomas.

The development of hepatocellular carcinoma (HCC) presumably occurs in multiple steps and is influenced by numerous factors. Hepatitis B virus (HBV) is strongly associated with the development of HCC in people chronically infected with the virus, but the mechanism of viral involvement remains unclear. One possibility is that the gross chromosomal alterations frequently observed in HCC DNA at the site of HBV integration may alter the expression of important nearby cellular genes. We previously reported the cloning and characterization of a HBV insert from a Chinese HCC. The viral insert mapped to chromosome 17p11.2-12, and cellular sequences were duplicated at the site of viral integration. In the present study a DNA probe derived from cellular DNA sequences adjacent to the previously characterized HBV insert was used to analyze a set of 19 matched normal liver and HBV-positive hepatoma samples obtained from the same region of China, near Shanghai. Tumor-specific DNA changes were detected in two additional HCCs, suggesting that the small region of chromosome 17p defined by the flanking cell DNA probe is commonly altered in hepatomas. Restriction fragment length polymorphism studies demonstrated that the loss of one copy of portions of chromosome 17 occurred in 10 (53%) of the 19 patients. The loss of one allele of the p53 gene (located on chromosome 17p13) occurred in at least 6 (60%) of the 10 patients who were heterozygous at the p53 locus. As the p53 gene is known to possess tumor suppressor activity, the functional loss of this gene may be a significant step in the development of a subset of HCCs. High levels of allele loss also were detected for chromosomes 8q (4 of 9; 44%) and 16p (5 of 6; 83%) and may indicate the presence of additional cellular genes whose functional loss is important in the development of HCCs.

Carcinoma, Hepatocellular↗

PubMed2004

[Traumatic lesion of the optic nerve head by flying fish: a case report].

BACKGROUND: Traumatic lesion to the optic nerve often leads to severe and persistent functional loss. HISTORY AND SIGNS: A male patient was transferred to our hospital from the University Eye Clinic of Guadeloupe 5 days after ocular injury caused by a flying fish. Visual function was light perception. The anterior part of the eye and retina were unremarkable. A computer tomography disclosed a fracture of the sphenoid sinus, with a little bone fragment (DD: foreign body) located close to the optic nerve. THERAPY AND OUTCOME: Therapy had been started with Aminopenicillin combined with clavulan acid (Augmentin) i. v., 500 ml methylprednisolone (Solumedrol) i. v., lysine-acetyl salicylate (Aspegic) and topical application of dexamethasone combined with neomycin/polymyxin B (Maxitrol). We continued this therapy and intensified it by adding nimodipine (Nimotop) 30 1-1-1 and acetazolamide retard (Diamox sustet) 1-0-1. Unfortunately visual function did not recover under therapy. CONCLUSIONS: Traumatic lesions of the optic nerve head, especially when due to axial or tangential forces, can lead to severe and irreversible functional loss. Severe traumatic lesions, even bone fractures induced by flying fish are not a seldom encounter in the Caribbean Sea.

Acetazolamide↗