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PubMedDate not supplied

Functional hearing loss and its relationship to resolved hearing levels.

The nature of functional hearing loss was retrospectively studied with respect to hearing sensitivity after resolution of the nonorganic components in 63 adults with bilateral exaggerated losses (126 ears). The configuration of the functional components (difference between the functional and resolved thresholds) was found to be related to that of the resolved hearing levels. The size of the functional overlay was essentially the same across the audiometric frequency range when the hearing was actually normal or if there was only mild loss. In cases of precipitously sloping high-frequency losses, the magnitude of the functional overlay became dramatically smaller for the impaired frequencies than for lower frequencies where hearing was normal or only mildly impaired. Moderate and severe losses represented a transitional situation, in which the functional components became gradually smaller with increasing frequency. Subjects with different resolved hearing in each ear (e.g., mild loss in one ear and a precipitous loss in the other) demonstrated nonorganic overlays that were consistent with the actual hearing levels for each respective ear. The findings suggest the use of an internalized, loudness level-based anchor by subjects with functional losses: the test signal must sound as loud as the anchor at each frequency in order for an exaggerated threshold response to be volunteered at that respective frequency. The pure-tone audiometric configuration and amount of functional loss at least in bilateral cases is thus consistently accounted for on the basis of known and explainable auditory factors.

Adult↗

PubMed1993

Perception of horizontal head and trunk rotation: modification of neck input following loss of vestibular function.

Chronic loss of vestibular function modifies the role of neck afferents in human perception of self-motion. We characterized this change by comparing the self-motion perception of patients with chronic vestibular loss (Ps) to that of normal subjects (Ns). Stimuli consisted of sinusoidal horizontal rotations (0.025-0.4 Hz) of the trunk relative to the head (neck stimulation) and/or of the head in space (vestibular stimulation). Perception of head rotation relative to the trunk, of trunk rotation in space, or of head rotation in space was assessed in terms of gain and phase (veridical perception, G = 1 and phi = 0 degree) as well as detection threshold using a pointing procedure. (1) Perception of head rotation relative to the trunk (neck proprioception). Ps' detection threshold of head-to-trunk rotation was normal (i.e. similar to that of Ns) across all frequencies tested. Also, with peak angular velocities above 5 degrees/s, the gain of their perception was approximately normal. When peak velocity was decreased below this value, however, either by lowering stimulus frequency with peak displacement kept constant (+/- 8 degrees) or by decreasing peak displacement at constant frequency (0.05 Hz), the gain increased above unity, unlike in Ns. In contrast, the phase remained normal (approximately 0 degree). (2) Perception of trunk rotation in space. Ps perceived their trunks as stationary during neck stimulation and all vestibular-neck combinations at medium to low frequencies. At 0.4 Hz, however, Ps consistently perceived the trunk rotation, conceivably due to somatosensory self-motion cues arising from high body acceleration. In contrast, Ns perceive a trunk-in-space rotation with the neck stimulation and most of the stimulus combinations across the whole frequency range tested. Ns perceived their trunks as stationary only during head rotation on the stationary trunk (presumed to reflect a mutual cancellation of neck and vestibular signals). (3) Perception of head rotation in space. In Ps, unlike Ns, this perception always resembled that of head rotation relative to the trunk. (4) When Ps were presented with a visual or somatosensory space reference (not motion cues), their perception of trunk and head rotation in space became approximately normal. (5) We suggest that there are basically two changes in the neck-induced self-motion perception associated with chronic vestibular loss. First, neck proprioception shows a non-linear gain that overemphasizes low stimulus velocities, for unknown reasons.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1999

Effect of internal thoracic artery preparation on blood loss, lung function, and pain.

BACKGROUND: Postoperative blood loss, respiratory distress, and pain after coronary artery operation were assessed in a prospective, randomized, clinical study comparing two techniques of internal thoracic artery preparation. METHODS: In group A (n = 57) the internal thoracic artery was dissected with the entire surrounding connective tissue after opening the pleura, using routine lateral pleural drainage. In group B (n = 55) a venoarterial pedicle was prepared without surrounding muscle leaving the pleura intact. We assessed blood loss, clinical outcome, lung function, location, intensity, and quality of pain 6 days and 3 months after the operation. RESULTS: Significantly higher blood loss was observed in group A (A, 608+/-58 mL; B, 470+/-48 mL; p = 0.027). Forced expiratory volume in 1 second was significantly decreased in group A 6 days after surgery (A, 76.0%+/-1.6%; B, 83.2%+/-1.6%; p = 0.020). The forced expiratory volume in 1 second correlated to inspiratory vital capacity, which confirmed the advantage of the venoarterial technique (A, 0.771+/-0.021; B, 0.832+/-0.020; p = 0.003). Vital capacity was significantly higher in the venoarterial group at 3 months (A, 85.2%+/-2.1%; B, 98.5%+/-1.2%; p = 0.009), but not on postoperative day 6. The incidence of pleural effusion and atelectasis was significantly higher in group A (effusion: A, 52.6%; B, 23.6%; p = 0.002; atelectasis: A, 42.1%; B, 20.0%, p = 0.015). Sternal pain (A, 36.8%; B, 9.1%; p = 0.001) and suspenders pain (A, 33.3%; B, 7.3%; p = 0.001) occurred more often in group A. When using a multidimensional pain score, patients in group A experienced significantly sharper (6 days: A, 6.7+/-0.3; B, 3.3+/-0.2; p = 0.018; 3 months: A, 3.5+/-0.3; B, 1.4+/-0.3; p = 0.046) and more annoying pain (6 days: A, 7.6+/-0.2; B, 2.7+/-0.1; p = 0.036; 3 months: A, 6.6+/-0.3; B, 2.3+/-0.2; p = 0.040). CONCLUSIONS: These results demonstrate that the venoarterial preparation technique is superior to conventional internal thoracic artery preparation regarding postoperative blood loss, lung function, and pain.

Female↗

PubMed2001

Functional alterations in gap junction channels formed by mutant forms of connexin 32: evidence for loss of function as a pathogenic mechanism in the X-linked form of Charcot-Marie-Tooth disease.

CMTX, the X-linked form of Charcot-Marie-Tooth disease, is an inherited peripheral neuropathy arising in patients with mutations in the gene encoding the gap junction protein connexin 32 (Cx32). In this communication, we describe the expression levels and biophysical parameters of seven mutant forms of Cx32 associated with CMTX, when expressed in paired Xenopus oocytes. Paired oocytes expressing the R15Q and H94Q mutants show junctional conductances not statistically different from that determined for Cx32WT, though both show a trend toward reduced levels. The S85C and G12S mutants induce reduced levels of junctional conductance. Three other mutants (R15W, H94Y and V139M) induce no conductance above baseline when expressed in paired oocytes. Analysis of the conductance voltage relations for these mutants shows that the reduced levels of conductance are entirely (H94Y and V139M) or partly (S85C and R15W) explicable by a reduced open probability of the mutant hemichannels. The R15Q and H94Q mutations also show alterations in the conductance voltage relations that would be expected to minimally (H94Q) or moderately (R15Q) reduce the available gap junction communication pathway. The reduction in G12S induced conductance cannot be explained by alterations in hemichannel open probability and are more likely due to reduced junction formation. These results demonstrate that many CMTX mutations lead to loss of function of Cx32. For these mutations, the loss of function model is likely to explain the pathogenesis of CMTX.

Amino Acid Substitution↗

PubMed2001

Phosphate-binding loop and Rab GTPase function: mutations at Ser29 and Ala30 of Rab5 lead to loss-of-function as well as gain-of-function phenotype.

Ras-like GTPases contain a structurally conserved GTP-binding domain. An important element of the GTP-binding domain is the phosphate-binding loop, which contains two Gly residues (Gly(12) and Gly(13)) in Ras. Because the two Gly residues are crucial for normal Ras function, it is intriguing that they are not conserved in other Ras-like GTPases, including the Rab GTPases; for example, the equivalent residues in Rab5 are Ser(29) and Ala(30). The present study builds on earlier biochemical characterizations of the Rab5 mutants containing substitutions at Ala(30) and provides a comprehensive analysis of the structure-function relationship of the Rab5 phosphate-binding loop. We have generated 19 new mutants containing amino acid substitutions at Ser(29) and determined whether these Ser(29) mutants, as well as the Ala(30) mutants, remain able to stimulate the endocytosis of horseradish peroxidase in baby hamster kidney cells. A total of 11 mutants lose the activity of stimulating endocytosis. Of these 11 mutants, 9 are defective in membrane association. In contrast, 27 mutants remain able to stimulate endocytosis. Five of them induce a novel cellular phenotype: cell rounding and detachment from culture dishes. They also induce super-large early endosomes such as the constitutively activated Rab5:Q79L mutant. Biochemical results suggest that the constitutive activation of Rab5 requires an increased nucleotide exchange rate and/or decreased GTPase activity. This study establishes functional significance for the phosphate-binding loop of Rab5 and shows that mutations in this region lead to either a loss-of-function or a gain-of-function phenotype, indicating a structure-function relationship distinct from that of Ras.

Alanine↗

PubMed2002

Extinction and the loss of functional diversity.

Although it is widely thought to influence ecosystem processes, there is little consensus on an appropriate measure of functional diversity. The two major perspectives, to date, are to assume that every species is functionally unique, or to assume that some species are functionally identical, such that functional groups exist. Using a continuous measure of functional diversity (FD) derived from the quantitative functional traits of species, we show that the loss of functional diversity from six natural assemblages was rapid compared with rates of loss from comparable simulated assemblages. Loss of FD occurred faster than loss of functional-group diversity in four of the six natural assemblages. Patterns of functional-group diversity loss depended on the number of functional groups and the number of species in an assemblage. Extinctions that occurred first for species with particular traits (e.g. low leaf nitrogen concentration, deep roots and large body size) caused greater loss of FD than expected by chance in four of the six natural assemblages. In two real assemblages, these trait-dependent extinctions had more severe effects on FD than our simulated worst-case extinction scenario. These data suggest that conserving a large proportion of the functional traits of species requires conserving a large proportion of all species.

Animals↗

PubMed1980

Developmental and psychodynamic issues related to cases of childhood functional hearing loss.

The literature is scant regarding the details of the personality organizations of children exhibiting functional hearing losses. Projective data gleaned from five clinical cases of childhood functional hearing loss is presented. The core pathology involves a poorly consolidated image of the self. Threats to the continuity and cohesiveness of the self are avoided through a form of selective inattention.

Adolescent↗

PubMed1993

Influence of cisplatin on the sensitivity of the rat sciatic nerve to local hyperthermia.

The influence of cisplatin on the sensitivity of the rat sciatic nerve to local hyperthermia was investigated. Rats received 1.7 mg/kg cisplatin i.p., twice a week for 6 weeks, up to a cumulative dose of 20.4 mg/kg. After termination of cisplatin treatment, a 5 mm segment of the nerve was locally heated at a temperature of 45 degrees C (5-30 min). Loss of motor function was assessed by means of the toe-spreading test, 24 h post heating. The calculated ED50 for control nerves was significantly (p < 0.01) larger than the ED50 for cisplatin treated rats; 16.3 +/- 1.1 min vs. 10.9 +/- 1.1 min. This indicates that nerves from cisplatin treated rats were more sensitive to heat than nerves from control rats (dose modifying factor = 1.5 +/- 0.2). Histopathological investigation of nerves after heat alone or after heat preceded by cisplatin confirmed these differences and showed that edema, vascular damage and axonal degenerative changes of axons and myelin sheaths occurred at lower heat doses when compared to control nerves. Recovery studies showed that cisplatin treatment before hyperthermia caused a delay in recovery from motor function loss of about 6 days. Cisplatin treatment after hyperthermia had no influence on recovery from motor function loss.

Animals↗

PubMed1993

Juvenile rheumatoid arthritis: pain-related and psychosocial aspects and their relevance for assessment and treatment.

Objective. To review literature in the area of juvenile rheumatoid arthritis that has focused on pain experience, functional losses, and psychosocial functioning. Methods. This article provides a critical review of research addressing these three primary issues. Results. Subjective and behavioral measures have been developed to assess pain in juvenile rheumatoid arthritis patients, but further work is needed to determine the validity and reliability of these instruments. Tools to assess functional losses in juvenile rheumatoid arthritis patients also appear promising in preliminary studies. Patients can be at risk for difficulties in psychosocial functioning, although research suggests that there are a variety of family, parental, and child variables that influence child and sibling adaptation. Methodologic shortcomings prevent definitive conclusions in this area. Conclusions. Although methodologic limitations have plagued this research in the past, new advances are facilitating improved understanding of children and adolescents with juvenile rheumatoid arthritis. Implications for future study with this challenging population are offered.

Activities of Daily Living↗

PubMed1998

Reduced activity of hypothalamic corticotropin-releasing hormone neurons in transgenic mice with impaired glucocorticoid receptor function.

Loss of central glucocorticoid receptor (GR) function is thought to be involved in the development of neuroendocrine and psychiatric disorders associated with corticotropin-releasing hormone (CRH) hyperactivity. The possible causal relationship between defective GR function and altered activity of CRH neurons was studied in transgenic mice (TG) expressing antisense RNA against GR. Immunocytochemical studies showed significant reductions in CRH immunoreactive neurons in the paraventricular nucleus (PVN) and in CRH and vasopressin (AVP) stores in the external zone of the median eminence. Concomitantly, stimulus-evoked CRH secretion from mediobasal hypothalami of TG mice in vitro was reduced significantly. However, CRH mRNA levels in the PVN of TG mice were marginally lower than those in wild-type (WT) mice. 125I-CRH binding autoradiography revealed no differences between WT and TG animals in any of the brain regions that were studied. Basal plasma corticosterone (cort) levels and 125I-CRH binding, CRH-R1 mRNA, POMC mRNA, and POMC hnRNA levels in the anterior pituitary gland were similar in WT and TG mice. Intraperitoneal injection of interleukin-1beta (IL-1beta) increased plasma cort levels, CRH mRNA in the PVN, and anterior pituitary POMC hnRNA similarly in WT and TG mice. The injection of saline significantly reduced anterior pituitary CRH-R1 mRNA levels in WT mice, but not in TG mice, whereas IL-1beta produced a decrease in these mRNA levels in both strains. The data show that long-term GR dysfunction can be associated with reduced activity of CRH neurons in the PVN and decreased sensitivity of pituitary CRH-R1 mRNA to stimulus-induced downregulation. Moreover, the hypothalamic changes observed in this model suggest that impaired GR function, at least if present since early embryonic life, does not necessarily result in CRH hyperexpression characteristics of disorders such as major depression.

Animals↗

PubMed2002

Optimal strategies for modeling the reciprocal of creatinine versus time in renal transplant recipients and patients with native chronic renal disease.

Few studies have evaluated the least squares (LS) or alternative regression methods to estimate loss of renal function using the reciprocal of creatinine over time in renal transplant recipients or have compared their performances in patients with chronic renal insufficiency (CRI). We evaluated the LS and alternative methods using the proportion of explained variance, measured by R2, and prediction of the final creatinine level. The study included two groups of transplant recipients: (1) patients who developed graft failure (FAIL; n = 31) and (2) patients with an episode of biopsy-proven acute rejection with or without subsequent renal function loss (BXAR; n = 98) and a third group of individuals with CRI (n = 28). The LS method performed poorly in both transplant groups (mean R2 range, 0.35 to 0.44; 32% to 45% with final creatinine(actual) - creatinine(predicted) +/- 0.05 mg/dL), but better in the CRI group (mean R2, 0.57; 75% with final creatinine(actual) - creatinine(predicted) +/- 0.05). The best alternative was the two-phase regression line after exclusion of outliers, which provided similar results across the FAIL, BXAR, and CRI groups (mean R2, 0.71, 0.64, and 0.73; 81%, 84%, and 96% with final creatinine(actual) - creatinine(predicted) +/- 0.05, respectively; P = not significant) and had the best performance in patients with greater nadir creatinine values. The LS method is not suited to measure kidney function loss in renal transplant recipients. Use of the two-phase regression line after exclusion of outliers is a more reliable method in renal transplant recipients, especially patients with impaired baseline function, and has results similar to those of patients with CRI.

Female↗

PubMed1999

Functional visual loss in amblyopia and the effect of occlusion therapy.

PURPOSE: The aim of this study was to define the nature of functional visual loss in amblyopia and to identify those subjects whose amblyopia is chiefly due to one or more of the following deficits: abnormal contour interaction, abnormal eye movements, abnormal contrast perception, or positional uncertainty. METHODS: Fifty amblyopic children with a mean age of 5.6+/-1.3 years were referred from diverse sources. In addition to routine orthoptic and optometric evaluation the principal visual deficits in the amblyopic eye of each subject were identified using the following measures of visual acuity: high contrast linear, single optotype, repeat letter and low contrast linear, plus Vernier and displacement thresholds. These measures were repeated as the children underwent a prescribed occlusion therapy regime, after parental consent. RESULTS: All amblyopic subjects demonstrated a functional loss in each of the tests used, and occlusion therapy appeared to improve all aspects of the amblyopia. High contrast visual acuity was not always the primary deficit in visual function, and when amblyopic subjects were divided according to their primary visual loss, this visual function was found to show the greatest improvement with treatment. CONCLUSIONS: These results suggest that to successfully identify the primary visual deficit and monitor the success of occlusion therapy it is necessary to assess other aspects of visual function in amblyopia.

Amblyopia↗

PubMed1989

Functional hearing loss in children.

This report reviewed 39 school-age children diagnosed as having a functional hearing loss utilizing auditory brainstem response (ABR) audiometry during the past 5 years at the Department of Otolaryngology, Kyushu University Hospital in Japan. Twenty-seven cases were females and 12 were males. Seven cases had a hearing loss unilaterally and 32 bilaterally. Although pure-tone audiometry revealed a variety of audiogram shapes, two-thirds of the cases had a flat or saucer-shaped audiogram with a mild to moderately severe hearing loss. ABR audiometry for the frequencies of 1, 2 and 4 kHz indicated a normal hearing threshold in 65 ears of 35 patients, and mild threshold elevations of at least one frequency in the remaining 6 ears of 4 patients. Three illustrative cases were demonstrated, and a discussion was held regarding the features in audiometric tests, and environmental factors surrounding the children with this condition. We emphasized that the physiological hearing measurement such as ABR audiometry should be performed when any discrepancy was noted between the patient's history and results of pure-tone audiometry, because of not infrequent occurrence of functional hearing loss.

Adolescent↗

PubMed1986

Protein kinase C phosphorylation at Thr 654 of the unoccupied EGF receptor and EGF binding regulate functional receptor loss by independent mechanisms.

To test the functional consequence of phosphorylation of the EGF receptor at Thr 654 by protein kinase C, the normal Thr 654 human EGF receptor cDNA or a mutant encoding an Ala 654 were expressed in heterologous cells. In cell lines expressing both the Thr 654 and Ala 654 receptors, functional cell-surface Thr 654 receptors were reduced or were totally lost, but were not degraded, following activation of protein kinase C by phorbol esters (TPA), whereas Ala 654 receptors were unaffected. These data suggest that protein kinase C regulates ligand-independent receptor binding and internalization via phosphorylation of Thr 654 of the EGF holoreceptor. Because EGF induces internalization and degradation of the Ala 654 EGF receptor, at least two independent mechanisms can serve to signal loss of functional EGF receptors.

Alanine↗

PubMed2001

A loss-of-function mutation of c-kit results in depletion of mast cells and interstitial cells of Cajal, while its gain-of-function mutation results in their oncogenesis.

Loss-of-function mutations of the c-kit receptor tyrosine kinase (KIT) result in depletion of mast cells and interstitial cells of Cajal (ICCs). In contrast, gain-of-function mutations of KIT induce neoplasms of mast cells and ICCs. In humans, the sites of mutations are different between mast cell neoplasms and those of ICCs. The former were found in the juxtamembrane domain between the transmembrane and tyrosine kinase domains, and the latter in the tyrosine kinase domain. Moreover, the mechanism of constitutive activation is different. Point mutations and/or deletions in the juxtamembrane domain induced the KIT dimerization, and the dimerized KIT was activated. A point mutation at the particular aspartic acid in the tyrosine kinase domain induced spontaneous activation without forming dimers. Mutations of the c-kit gene are a good model for understanding the relationship between mutations and diseases in both humans and mice.

Animals↗

PubMed2003

Prevalence of organic neuro-ophthalmologic disease in patients with functional visual loss.

PURPOSE: To determine the concurrence of various patterns of functional visual loss (FVL) and organic disease. DESIGN: A retrospective case series in a university neuro-ophthalmology practice. METHODS: A retrospective case series in which we reviewed the clinical histories and neuro-ophthalmologic examinations of 133 consecutive patients diagnosed with FVL between July 1999 and August 2001. Functional visual loss was defined as an apparent afferent or efferent dysfunction that was unassociated with or far out of proportion with an identifiable lesion of the visual pathways. RESULTS: A total of 133 patients were identified. Nineteen were pediatric, and 76 were female. Fifty-six had concurrent head or eye pain. Nineteen had a recent history of trauma, and 17 had a recent surgical procedure. The most common pattern of FVL was a normal visual field in the presence of reduced visual acuity. Seventy-one patients (53%) with FVL presented with abnormal neuro-ophthalmologic examinations. Thirteen patients had central scotomata, and all had concurrent retinal or optic nerve pathology. Only 18 patients had a known disability claim pending. CONCLUSION: Although FVL was found in patients with no pathology, it was more common to find objective abnormalities on examination. This concurrence rate underscores the clinical necessity for following patients closely despite the diagnosis of FVL. No pattern of visual field constriction was routinely predictive of ophthalmologic or neurologic pathology except the presence of a central scotoma. The presence of a central scotoma in a nonorganic visual field should alert the practitioner to search for organic pathology.

Adolescent↗

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↗

PubMed1984

Malocclusion at adolescence related to self-reported tooth loss and functional disorders in adulthood.

It has been argued that malocclusion may predispose to tooth loss and functional disorders of the masticatory system. It was the purpose of this study to examine relationships between untreated malocclusion, recorded at adolescence, and self-reported tooth loss and functional disorders in adulthood. In 1965-66, the occurrence of morphologic traits of malocclusion was recorded in 977 Danish adolescents who did not have access to organized orthodontic care. Fifteen years later, 841 (86%) of these subjects responded to a questionnaire screening for tooth loss, symptoms involving the temporomandibular joints and muscles, and some other symptoms of dysfunction. The occurrence of malocclusion was related to the symptoms of the temporomandibular joints and muscles and other functional symptoms. Only a few significant coefficients of correlation were observed. Extreme maxillary overjet (greater than 9 mm) and frontal open bite showed significant correlations with unsatisfactory biting ability. Crossbite was correlated positively with speech defects but negatively with tenderness or fatigue of the cheeks; unilateral crossbite was associated with locking of the mandible. It was concluded that the untreated morphologic traits of malocclusion did not seem to predispose to tooth loss or functional disorders of the masticatory system as reported at the age of 30 years.

Adolescent↗