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Sensing and controlling rotational orientation in normal subjects and patients with loss of labyrinthine function.

The disability resulting from uni-or bilateral loss of vestibular function was assessed by exposing subjects, in darkness, to random rotational displacements on a motorized chair away from a "center" position and requiring them to rotate themselves back to center using a "joystick" control. Normal subjects were accurate within 10 to 15 percent over 180-degree rotations. Alabyrinthine subjects failed to sense their rotation to any useful extent. Subjects with unilateral loss of function as a result of surgery produced hypometric responses to ipsilateral rotation and large amplitude, but inaccurate responses to contralateral rotation. This pattern became more symmetric and normometric with adaptation to loss of function. The procedure promises to be a more useful measure of adaptation than assessing vestibulo-ocular reflexes.

Adult↗

Genetic and epigenetic alterations of 9p21 gene products in benign and malignant tumors of the head and neck.

The multistep process of tumorigenesis has not been decoded to date, although numerous investigations into probable molecular changes have meanwhile been conducted. However, not only DNA changes or loss of alleles cause deregulation of gene function, but also epigenetic alterations (e.g. methylation) result in functional loss. The INK4a-ARF (CDKN2A) locus, located on chromosome 9p21, encodes two functionally distinct tumor suppressor genes, p14ARF and p16INK4a, which play active roles in the p53 and Rb tumor suppressive pathways. We therefore examined not only p16 and p14 proteins, but also alterations of the INK4a-ARF locus, including methylation and loss of heterozygosity in benign and malignant tumors of the head and neck (squamous cell carcinomas and pleomorphic adenomas). In benign pleomorphic adenomas, methylation of p14ARF was found in 1 out of 42 (2%) cases, whereas alterations of p16INK4a occurred in 12/42 (29%) pleomorphic adenomas. In HNSCC, methylation of p16INK4a occurred in 16 out of 50 (32%) carcinomas. P14ARF was found to be methylated in 8 out of 50 cases (16%). Our results demonstrate that alterations of the INK4a-ARF locus are frequent and important events not only in the carcinogenesis of malignant, but also in benign tumors.

Adenoma, Pleomorphic↗

Visual perception and phenomenal consciousness.

In the (re-)animated debate on consciousness we focus on three questions: Who has consciousness? What is its neuronal basis? What is its function? Regarding the first, we suggest that consciousness is exclusive to living organisms able to distinguish self from non-self. It may be restricted further to organisms who possess a repertoire of overt and covert behaviour which can be voluntarily modified and suppressed. This requires an intermediary neuronal net mediating between sensory input and behavioural output. What are the properties of this net which distinguish unalloyed information processing per se from conscious representation? To tackle this second question, we use the visual system and the functional losses that result from lesions at its different levels, and differentiate a reflexive, a phenomenal, and a consciously accessible stage of visual processing. We suggest that the latter two represent two distinct aspects of consciousness. Blindsight, a neurological example of visual processing in the absence of phenomenal vision, could help to elucidate the neuronal basis of phenomenality, and the special role of striate cortex. Like the patients, our monkeys with unilateral striate cortical removal show evidence not just of residual visual processing, but of the same absence of phenomenal vision, opening routes to further exploring the details of its neuronal implementation. The second aspect, conscious access to presently or previously processed information, is likely to require higher cortical structures, and may depend on the stage of phenomenal representations. In patients with blindsight, both aspects are lost, and it is conceivable that a loss of phenomenality generally causes a loss of conscious accessibility. One important function of phenomenal representations, our third question, would then be to allow conscious retrieval and manipulation of currently processed or formerly stored information, enabling organisms to consciously think and plan.

Animals↗

Evaluation of DNA damage in rainbow trout (Oncorhynchus mykiss) and gilthead sea bream (Sparus aurata) cryopreserved sperm.

Cryopreservation causes several types of damage to spermatozoa, such as loss of plasma membrane integrity and functionality, loss of motility, and ATP content, resulting in decrease of fertility rates. This spermatozoal damage has been widely investigated for several marine and freshwater fish species. However, not much attention has been paid to the nuclear DNA. The objective of this study was to determine the degree to which cryopreservation induces spermatozoal DNA damage in two commercially cultured species, rainbow trout (Oncorhynchus mykiss) and gilthead sea bream (Sparus aurata), both of which could benefit from the development of cryopreservation strategies on a large scale. We have used the single-cell gel electrophoresis, commonly known as Comet assay to detect strand breaks in DNA. This technique was performed on fresh and cryopreserved sperm from both species. In rainbow trout there was a significant increase in the averages of fragmented DNA and Olive tail moment after cryopreservation (11.19-30.29% tail DNA and 13.4-53.48% Olive tail moment in fresh and cryopreserved sperm, respectively), as well as in the proportion of cells with a high percentage of DNA fragmentation. For gilthead sea bream there were no significant differences in the percentage of tail DNA between the control samples and sperm diluted 1:6 and cryopreserved (28.23 and 31.3% DNA(t), respectively). However, an increase in the sperm dilution rate produced an increase in the percentage of DNA fragmentation (41.4%). Our study demonstrates that cryopreservation can induce DNA damage in these species, and that this fact should be taken into account in the evaluation of freezing/thawing protocols, especially when sperm cryopreservation will be used for gene bank purposes.

Animals↗

DPOAE level shifts and ABR threshold shifts compared to detailed analysis of histopathological damage from noise.

A detailed comparison of 2f(1)-f(2) distortion product otoacoustic emission (DPOAE) level shifts (LS) and auditory brainstem response (ABR) threshold shifts with noise-induced histopathology was conducted in chinchillas. DPOAE levels (i.e., L(1) and L(2)) at f(1) and f(2), respectively, ranged from 55-75 dB sound pressure level (SPL), with f(2)/f(1)=1.23, 6 points/octave, f(2)=0.41-20 kHz, and ABR thresholds at 0.5-20 kHz, 2 points/octave, were determined pre-exposure. The exposure was a 108 dB SPL octave band of noise centered at 4 kHz (1-1.75 h, n=6) or 80-86 dB SPL (24 h, n=5). DPOAE LSs (magnitude pre- minus post-exposure) and ABR threshold shifts (TS) were determined at 0 days and up to 28 days post-exposure. The cochleae were fixed, embedded in plastic and dissected into flat preparations. The length of the organ of Corti (OC) was measured; missing inner (IHC) and outer (OHC) hair cells counted; stereocilia damage rated; and regions of OC and nerve-fiber loss determined. Cytocochleograms were made showing functional loss and structural damage with the LS and TS overlaid. Some unexpected results were obtained. First, the best correlation of LS with histopathology required plotting the DPOAE data at f(1) with respect to the chinchilla-place map. The best correlation of TS was with IHC and nerve-fiber loss. Second, wide regions of up to 10% scattered OHC loss in the apical half of the OC showed little or no LS. Third, with the 108 dB SPL noise, there was 20-40 dB of recovery for DPOAEs at mid-high frequencies (3-10 kHz) in eight of 12 cochleae where there was 70-100% OHC loss in the basal half of the OC. The largest recovery at mid-high frequencies occurred in regions where the OC was entirely missing. Fourth, with the 80-86 dB SPL noise, there was no LS at small focal lesions (100% loss of OHCs over 0.4 mm) when the frequency place of either f(1) or f(2) was within the lesion but not both. There was no correlation of LS with OHC stereocilia loss, fusion or disarray. These results suggest that, after noise exposure, DPOAEs at mid-high frequencies can originate from or be augmented by generators located at someplace other than the frequency place of f(2), possibly the basal 20% of the OC when this region is intact. Also, noise-induced DPOAE LSs seemed to reflect differing mechanisms for temporary and permanent hearing loss.

Animals↗

Rod photoreceptor transduction is affected in central retinal vein occlusion associated with iris neovascularization.

Patients with central retinal vein occlusion who later develop iris neovascularization show changes in the amplitude, the timing, and the sensitivity of the electroretinogram beta wave. We determined the extent to which rod photoreceptor dysfunction contributes to these changes by recording single-flash electroretinograms from both eyes of 52 patients with unilateral central retinal vein occlusion and fitting the leading edges of alpha waves with a model of rod phototransduction. Eyes with central retinal vein occlusion showed reductions in photoreceptor gain but no changes in photoreceptor amplitude when compared with the fellow eyes. The reductions were larger in eyes that developed iris neovascularization and were predictive of this complication. Photoreceptor gain reductions accounted for only part of the beta-wave timing delays and sensitive loss; the remainder is attributed to functional loss in the inner nuclear layer.

Adult↗

A new approach to assessing function in elderly people.

Current functional assessment methods and measures of elderly people are limited in their ability to detect small decrements in function or in discriminating between different patterns of functional loss. Nor do they directly assess function in the patient's usual environment. Recent technological advances have led to the development of small, wearable microelectronic devices that detect motion, velocity and acceleration. These devices can be used to develop new tools for more precise monitoring, assessment, and prediction of function by characterizing the 'electronic signatures' of successful or unsuccessful task-specific performance, and to allow for continuous assessment in a home environment. This presentation will summarize current efforts to translate new technologies into a clinical and research tool for improved assessment, monitoring, and prediction of function among older individuals.

Acceleration↗

Second metatarsophalangeal joint: biomechanics and reconstruction potential.

A damaged distal radioulnar joint results in instability, pain, and loss of motion. This amounts to function loss. Of the many proposed reconstructive procedures, only a vascularized joint transfer offers growth potential in children and durability. The well-studied vascular anatomy and minimal donor morbidity of the second metatarsophalangeal joint makes it a potentially useful source. The authors evaluated various biomechanical aspects of the second metatarsophalangeal joint, which included the mediolateral arc of movement of the second metatarsophalangeal joint in hyperextension when subjected to lateral stress loading; the different patterns of disruption at peak load; and the flexion and extension range of movement. Twenty-six cadaveric specimens were tested with a customized jig. The results showed that the mediolateral arc of movement of 114 degrees approximates that of the flexion and extension range of movement of 114.2 degrees. However, it differed in that it was equal in both directions, compared with an extension arc that was greater than a flexion arc. The peak load was approximately 100 N, and this resulted in fracture, avulsion, and ligament tear. These biomechanical results may be useful to reconstructive surgeons.

Adult↗

[Psychotherapeutic interventions in cancerology].

The task of a psychoanalyst working in cancerology is to help patients and families cope with the illness and the treatments by recognizing them all as "subjects" with their own phantoms, desires and personal history. Above all, the cancer patient is concerned by possible losses: loss of an essential body-function, loss of a social and/or economical status and finally loss of life itself. From our experience; we know that relieving pain is not only a question of prescribing the right medication but depends mostly on the way the team is able to recognize fears, conflicts and treat the person globally, offering solutions to solve the problems patients and families meet.

Attitude to Death↗

[Information value of the compartimental analysis of potassium metabolism for clinical medicine].

1. The special information value of the dynamic compartment analysis consists in functional evidence concerning the potassium metabolism. 2. Basis of the dynamic compartment analysis is an open central 3 compartment model. 3. The rate of metabolism which is determined by size of the pool and constant of speed is the most important parameter. 4. The mathematical modelling of the tracer course renders visible the compartmental effects of inflow and outflow of the speed constant. 5. Disturbances of the very quickly and quickly exchanging constituents of the potassium metabolism reflect themselves perhaps directly as a functional loss of the permanent and latent functional capacity of the organism.

Extracellular Space↗

Functional advantage after radical segmentectomy versus lobectomy for lung cancer.

BACKGROUND: Although several reports have recently demonstrated that segmentectomy for small-sized N0 lung cancer leads to recurrence and survival rates equivalent to those associated with lobectomy, controversy regarding the postoperative functional advantage in the former over the latter still persists. The purpose of this study was to evaluate the degree of postoperative functional loss in patients undergoing segmentectomy or lobectomy for lung cancer. METHODS: We analyzed patients able to tolerate lobectomy, who underwent radical segmentectomy (n = 38) or lobectomy (n = 45) for non-small-cell lung cancer. Functional testing included forced vital capacity, forced expiratory volume in 1 second, and anaerobic threshold measured preoperatively and at 2 and 6 months after surgery. RESULTS: Preoperative function tests showed no differences between segmentectomy and lobectomy patients. A positive and significant correlation was found between the number of resected segments versus loss of forced vital capacity (r = 0.518, p < 0.0001 at 2 months; r = 0.604, p < 0.0001 at 6 months) and loss of forced expiratory volume in 1 second (r = 0.492, p < 0.0001 at 2 months; r = 0.512, p < 0.0001 at 6 months). The postoperative reduction of forced vital capacity (p = 0.0006) and forced expiratory volume in 1 second (p = 0.0007) was significantly less in the segmentectomy group; however, a marginally significant benefit was observed in this group for anaerobic threshold (p = 0.0616). CONCLUSIONS: The extent of removed lung parenchyma directly affected that of postoperative functional loss even at 6 months after surgery, and segmentectomy offered significantly better functional preservation compared with lobectomy. These results indicate the importance of segmentectomy for early staged lung cancer.

Carcinoma, Non-Small-Cell Lung↗

Defining the nature of motion perception deficits in glaucoma using simple and complex motion stimuli.

PURPOSE: The purpose of this study is to determine the nature of motion perception deficits in primary open-angle glaucoma by measuring the sensitivity of simple (luminance-defined) and complex (texture-defined) motion, the latter requiring supplementary neural processing to be resolved. These findings will help address the possible extent of the cortical damage in glaucoma that has been recently demonstrated by anatomic and physiological studies. They also serve the purpose of establishing which motion paradigms would be most appropriate for assessing glaucoma-related functional loss. METHODS: Direction-identification thresholds for first-order and second-order motion were measured for 26 patients with primary open-angle glaucoma (for both phakic and pseudophakic) and 18 nonglaucomatous observers. RESULTS: The glaucomatous observers showed significantly increased motion thresholds for both first- and second-order motion conditions when compared with nonglaucomatous observers. However, the relative increase in threshold for first-order motion did not differ significantly from that of second-order motion. CONCLUSIONS: These findings imply that there is no measurable higher-level cortical function damage caused by the glaucomatous process because no greater loss in second-order motion was observed. Based on the results, we suggest that motion paradigms used to assess functional loss in primary open-angle glaucoma should consist of simple, first-order type stimuli to minimize potential confounds such as those introduced by both the normal and pathologic aging process on complex motion processing (i.e., perimetry using complex motion stimuli).

Aged↗

Genome organization, function, and imprinting in Prader-Willi and Angelman syndromes.

The chromosomal region, 15q11-q13, involved in Prader-Willi and Angelman syndromes (PWS and AS) represents a paradigm for understanding the relationships between genome structure, epigenetics, evolution, and function. The PWS/AS region is conserved in organization and function with the homologous mouse chromosome 7C region. However, the primate 4 Mb PWS/AS region is bounded by duplicons derived from an ancestral HERC2 gene and other sequences that may predispose to chromosome rearrangements. Within a 2 Mb imprinted domain, gene function depends on parental origin. Genetic evidence suggests that PWS arises from functional loss of several paternally expressed genes, including those that function as RNAs, and that AS results from loss of maternal UBE3A brain-specific expression. Imprinted expression is coordinately controlled in cis by an imprinting center (IC), a genetic element functional in germline and/or early postzygotic development that regulates the establishment of parental specific allelic differences in replication timing, DNA methylation, and chromatin structure.

Angelman Syndrome↗

Blockade of dopamine transporter and tyrosine hydroxylase activity loss by [D-Ala(2), D-Leu(5)]enkephalin in methamphetamine-treated CD-1 mice.

[D-Ala(2), D-Leu(5)]enkephalin (DADLE) has been previously reported to prolong the survival of tissues both in the periphery and in the central nervous system. Here, we show that DADLE was able to block the protein as well as the functional loss of dopamine transporter (DAT) and tyrosine hydroxylase (TH) induced by methamphetamine. Male CD-1 mice received four injections of methamphetamine (10 mg/kg, i.p. ) at 2-h intervals. DADLE (4 mg/kg, i.p.) was given 30 min before each injection of methamphetamine. Western blotting and enzymatic assays showed that DADLE blocked the protein loss and functional impairment of DAT and TH induced by methamphetamine.

Analysis of Variance↗

Osteoblastic insufficiency is responsible for maintenance of osteopenia after loss of ovarian function in experimental beagle dogs.

Bone loss developing after cessation of ovarian function in humans represents a major health problem. To establish the value of ovariohysterectomy in female beagle dogs as a model for bone loss and to study static and dynamic parameters of bone associated with the negative bone balance occurring after cessation of ovarian function, we performed iliac crest bone biopsies before and 4 months after ovariohysterectomy in eight beagle dogs and in five sham-operated controls. Cessation of ovarian function was documented by an increase in serum levels of LH 4 weeks after ovariohysterectomy. There was no change in serum calcium, phosphorus, and creatinine during the 4 months of the study. Cancellous bone mass and trabecular mean wall thickness decreased significantly after ovariohysterectomy (P less than 0.01). In addition, the number of osteoblasts was increased and the bone formation rate per osteoblast, that is, the activity of bone-forming cells, was decreased (P less than 0.01). Parameters of bone resorption were not significantly altered in the animals with ovariohysterectomy. No changes in histomorphometric parameters of bone structure, formation or resorption were observed in the sham-operated controls. These data indicate that ovariohysterectomy in beagle dogs may serve as a useful model for bone loss associated with cessation of ovarian function. Osteoblastic insufficiency appears to play a major role in the maintenance of bone loss occurring after ovariohysterectomy in beagle dogs.

Amenorrhea↗

On-line learning in changing environments with applications in supervised and unsupervised learning.

An adaptive on-line algorithm extending the learning of learning idea is proposed and theoretically motivated. Relying only on gradient flow information it can be applied to learning continuous functions or distributions, even when no explicit loss function is given and the Hessian is not available. The framework is applied for unsupervised and supervised learning. Its efficiency is demonstrated for drifting and switching non-stationary blind separation tasks of acoustic signals. Furthermore applications to classification (US postal service data set) and time-series prediction in changing environments are presented.

Algorithms↗

Cardiopulmonary exercise testing in the preoperative assessment for lung resection surgery.

Whereas pulmonary function tests (PFTs) initially identify high-risk pulmonary patients being evaluated for lung resection surgery, other diagnostic modalities, including cardiopulmonary exercise testing (CPET) and/or split function studies, are then necessary for a more accurate assessment. CPET including VO2max have emerged as integral components of a step approach for the physiologic assessment for lung resection surgery. Increasingly, CPET is being used because it provides the best index of functional capacity and global O2 transport (VO2max) as well as estimating both cardiac and pulmonary reserves not available from other modalities. CPET permits the detection of clinically occult heart disease and provides a more reliable estimate of functional capacity postoperatively compared with PFTs, which routinely overestimate functional loss after lung resection. Currently, though split function studies are clearly established and have traditionally been used before CPET in preoperative decision analysis, recent work favors using CPET including VO2max before split function studies because VO2max % predicted is a good independent predictor of risk. Importantly, both studies are complementary and optimize assessment of surgical risk; this is particularly valuable for borderline patients, so that opportunity for curative resection is not denied.

Carcinoma, Non-Small-Cell Lung↗

The association of myasthenia gravis and connective tissue diseases--the role of Sjøgren's syndrome.

The symptoms of myasthenia gravis (MG) reflect the loss of neuromuscular transmission due to the functional loss of the acetylcholine receptor. We reviewed the reported association of MG and connective tissue diseases including rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis (PSS), polymyositis and dermatomyositis, mixed connective tissue disease (MCTD) and Sjøgren's syndrome (SjS). We found that the association of MG and MCTD or PSS is rare. We also reviewed the role of D-penicillamine, thymus abnormalities and the coexistence of SjS as one of the underlying pathological conditions for the association of MG and various connective tissue diseases.

Connective Tissue Diseases↗