Biomedical subjects
Publications and source records attributed to D Huppert.
We examined 103 patients with vestibular neuritis (VN) in a follow-up study (5.7 to 20.5 years, mean 9.8 years). Two patients (1.9%) had developed a second occurrence of VN 29 to 39 months after the first. VN affected the contralateral ear in both and caused less severe distressing vertigo and postural imbalance. Unlike Bell's palsy and sudden hearing loss, a relapse in the same ear did not occur.
One hundred and six patients diagnosed between 1987 and 1998 to have somatoform phobic postural vertigo were examined in a follow-up study with a self-evaluating questionnaire. The improvement rate after a mean follow-up time of 8.5 years (5 to 15.9 years) was 75% (27% of the patients reported a complete remission). While the majority of these patients experienced improvement or remission during the first year after assessment of diagnosis and a short-term psychotherapeutic approach, some patients also had considerable improvement even after two or more years. There was a negative correlation between the duration of the condition before assessment of the diagnosis and the improvement/regression rate. The improvement/regression rate was independent of gender, age, preceding vestibular or non-vestibular organic disorders, and the various medical, physical, or psychotherapeutic interventions. Transient relapses occurred in 47% of the improved patients once or repeatedly. The probability of developing a relapse remained constant throughout the entire follow-up. None of the patients required a revision of the initial diagnosis on the basis of the questionnaire.
We provide a first experimental verification of a theoretical prediction of a kinetic transition in a reversible binding reaction, AB right harpoon over left harpoon A+B, driven by the difference in effective lifetimes of the bound and the unbound states. We consider the kinetics of excited-state proton transfer to solvent from a photoacid whose conjugate anionic base possesses an extremely short unbound anion lifetime. Its solvent variation relative to the overall dissociation rate coefficient induces a transition in the kinetics, from power law to exponential.
Pyranine (8-hydroxy pyrene-1,3,6-trisulfonate) is a commonly used photoacid that discharges a proton when excited to its first electronic singlet state. Follow-up of its dissociation kinetics reveals the physicochemical properties of its most immediate environment. At vanishing ionic strength the dye adsorbs to the Escherichia coli lactose permease with stoichiometry of 1:1 and an association constant of 2.5 x 10(5) M(-1). The reversal of the binding at high ionic strength and the lower pK value of the bound dye imply that positive charge(s) stabilize the dye in its site. The fluorescence decay curve of the bound dye was measured by time-correlated single photon counting and the measured transient was subjected to kinetic analysis based on the geminate recombination model. The analysis indicated that the binding domain is a cleft (between 9 and 17 A deep) characterized by low activity of water (a((water)) = 0.71), reduced diffusivity of protons, and enhanced electrostatic potential. The binding of pyranine and a substrate are not mutually exclusive; however, when the substrate is added, the dye-binding environment is better solvated. These properties, if attributed to the substrate-conducting pathway, may explain some of the forces operating on the substrate in the cavity. The reduced activities of the water strips the substrate from some of its solvation water molecules and replace them by direct interaction with the protein. In parallel, the lower dielectric constant enhances the binding of the proton to the protein, thus keeping a tight seal that prevents protons from diffusing.
Forty-two patients with phobic postural vertigo took part in a neurological and psychiatric follow-up study. During the follow-up time of about 2.5 years the neurological diagnosis remained stable (41 of 42 patients). PPV can be assigned to various psychiatric categories according to DSM-III-R. Although an association of PPV with anxiety disorders is evident, not all patients present with symptoms of anxiety or panic during attacks of vertigo. However most patients develop a disabling "phobic-avoidance pattern" with recurrent attacks. Important psychosocial stressors can be identified at the onset of the condition. Motives of secondary gain have also to be taken into consideration. The course of illness varies depending on the neurological syndrome of vertigo, on the one hand, and concomitant psychopathological syndromes, on the other. Despite a considerable rate of improvement in vertigo complaints (79%), the group of patients with phobic postural vertigo as a whole presented with significant psychological problems at follow-up term (74%), requiring specific psychiatric and/or psychotherapeutic interventions. Dependent or avoidant personality, and hypochondria were prognostic of a more negative course of illness.
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Seventy-eight patients with phobic postural vertigo (PPV) and 17 patients with psychogenic disorder of stance and gait (PSG) were asked to evaluate their condition 6 months to 5.5 years after their original referral and short-term psychotherapy. Two results seem most important: (1) PPV had a favorable course with a 72% improvement rate (22% of patients becoming symptom free), whereas the majority of patients with PSG (52%) remained unchanged; (2) the majority of patients with PPV experienced complete remission or considerable improvement even if their condition had lasted between 1 and 20 years prior to diagnosis. Complete remission of PSG was observed only if the disorder has been present less than 4 months; there was no improvement if it had lasted longer than 2 years. PPV can be defined as a distinct clinical entity with a relatively benign course. It can be reliably diagnosed on the basis of typical features.
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Explore the source record for details and available documents.
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Thirty-seven patients with psychogenic disorders of stance and gait were clinically evaluated, recorded on video, and analysed with regard to clinical phenomenology. Characteristic, suggestive and unspecific features were identified. Six characteristic features proved most valuable for diagnosis of psychogenesis, as they occurred alone or in combination in 97% of patients: (1) momentary fluctuations of stance and gait, often in response to suggestion; (2) excessive slowness or hesitation of locomotion incompatible with neurological disease; (3) "psychogenic" Romberg test with a build-up of sway amplitudes after a silent latency or with improvement by distraction; (4) uneconomic postures with wastage of muscular energy; (5) the "walking on ice" gait pattern, which is characterized by small cautious steps with fixed ankle joints; (6) sudden buckling of the knees, usually without falls. Seventy-three percent of patients had additional suggestive features. Classification into characteristic subtypes was not found useful because predominant features varied from patient to patient and occurred in various combinations. Factitious impairment of stance and gait was studied in 13 healthy drama students. Simulated gait dysfunction appeared less conspicuous and more difficult to diagnose than the clinical psychogenic disorders.
A 34-year-old male patient developed a neurological disorder and signs of cerebellar degeneration, with antibodies against Purkinje cells in the serum, a syndrome previously described as "paraneoplastic cerebellar atrophy". Antibody reaction of the patient's serum was demonstrated by immunohistochemistry on sections through the rat and human cerebellum. Purkinje cells demonstrated granular staining of cytoplasmic proteins and proximal dendrites with nuclear sparing. In an immunoblot, the antibodies from the patient's serum reacted with proteins from an extract of rat cerebellum. Only a few distinct proteins from the complex mixture of cerebellar proteins were found to bind with the serum antibodies when using a combination of affinity chromatography and sodium dodecyl sulphate (SDS) gel electrophoresis. The molecular masses of the proteins differed significantly from those identified in patients reported in the literature. Protein denaturation by SDS and 2-mercaptoethanol resulted in a decrease of antibody binding capacity. After immunosuppressive therapy and plasmapheresis, the reaction of the patient's serum with Purkinje cells was greatly diminished; however, only slight clinical improvement was observed. No sign of neoplasm could be found with repeated examinations. The immunological aspects of this case suggest that cerebellar degeneration may be linked to a previously unreported autoimmune response.
By adsorption of pyranine (8 hydroxypyrene 1, 3, 6 trisulfonate) to lysozyme we create on the positively charged protein a fluorophoric site with a total charge of -3. Photo dissociation of the dye's hydroxyl proton changes its absorption and fluorescence spectrum, permitting a continuous monitoring of the reprotonation dynamics. Absorbance measurements in the microsecond time scale monitor how the bulk protons penetrate the Coulomb cage of the bound dye. Time-resolved fluorescence monitors how the proton is escaping out of the Coulomb cage of the bound dye. These probe reactions were studied with a series of dye-enzyme complexes where the number of free carboxylate was reduced by amidation, increasing the total charge of the complex from +5 to +12.6. The time-resolved measurements demonstrate the complexity of the electric field in the immediate vicinity of the dye. It is consistent with a negative potential wall (of the anion) surrounded by a positive potential wall of proteinaceous moieties.
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The water layers interspacing between the phospholipid membranes of a multilamellar vesicle are 3-10 water layers across and their width is adjusted by osmotic pressure (Parsegian, V.A., et al., 1986. Methods Enzymol. 127:400-416). In these thin water layers we dissolved pyranine (8 hydroxypyrene 1,3,6 trisulfonate), a compound which, upon photo excitation, ejects it hydroxy proton with time constant of 100 psec. (Gutman, M. 1986. Methods Enzymol. 127:522-538). In the present study we investigated how the width of the aqueous layer, the density of phosphomoieties on the membrane's surface and the activity of water in the layer affect the capacity of protons to diffuse out from the electrostatic cage of the excited anion before it decays to the ground state. Using a combination of steady-state and subnanosecond time-resolved fluorescence measurements we determined the average number of proton excited-anion recombinations before the proton escapes from the Coulomb cage. The probability of recombination in thin water layer is significantly higher than in bulk. The factor contributing most to enhancement of recombination is the diminished water activity of the thin aqueous layer. The time frame for proton escape from an electrostatic trap as big as a membrane-bound protein is 3 orders of magnitude shorter than turnover time of membrane-bound enzymes. Thus the effects of local forces on proton diffusion, at the time scale of physiological processes, is negligible.
Among 4470 consecutive neurological inpatients presenting "with typical neurological symptoms" 405 (9%) were found to have psychogenic rather than neurological dysfunction of the nervous system as the primary cause of admission. This probably represents a conservative figure, since secondary and minor pseudoneurological symptoms were not included. Retrospective analysis of these cases showed that pain was the most common psychogenic symptom, followed by motor symptoms (in particular stance and gait disturbances), dizziness, psychogenic seizures, sensory symptoms, and visual dysfunction. Unilateral motor and sensory symptoms were equally distributed to the left and right side of the body. Psychiatric abnormalities in these patients were heterogenous. Depressive syndromes were most common (38%), whereas hysterical features were less frequent than expected (9%). On discharge, improvement was significantly better for patients with recent onset of symptoms (2 weeks or less) than for those with longstanding disturbances. Short-term outcome was best for motor symptoms and worst for pain. Improvement was independent of psychiatric findings, coexistence of a neurological disease, age, and sex.