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Biomedical subjects

D Yarnitsky

Publications and source records attributed to D Yarnitsky.

At least 55 records · Page 3Linked to original sources

Paradoxical heat sensation in uremic polyneuropathy.

Sensory aspects of uremic neuropathy were studied in 36 patients using clinical assessment and quantitative sensory tests (QST). The outstanding abnormality in sensory quality was perception of heat in response to low temperature stimuli. This paradoxical heat sensation was found in the foot in 42% (15) of patients, far beyond the normal prevalence of 10%. Paradoxical sensation was positively related to cold hypoesthesia (P = 0.0004) suggesting disinhibition as a possible mechanism. Paradoxical heat sensation also positively related to creatinine level (P = 0.0012). Pruritus was present in 20 patients (56%), intensity not related to any biochemical or clinical parameter. Signs of sensory polyneuropathy (PNP), based on at least two abnormal parameters in the clinical assessment or QST, were found in 39% of patients (14), of whom 11 had paradoxical heat sensation. Thus, in 4 patients (11%), this sensory aberration preceded other signs for PNP. Paradoxical heat sensation seems to be a common and often early expression of the sensory neuropathy in uremia.

Adolescent↗

Heat pain thresholds: normative data and repeatability.

Measurement of thresholds for heat-induced pain was performed on 106 normal subjects, at thenar eminence and foot dorsum, using the reaction time-inclusive method of limits. Tests were repeated 2 weeks following the first test for most of the subjects. After determination that there were no outlying data points and that there was no systematic relationship between magnitude and variability of test scores, data from between 72 and 76 subjects were used to define normal upper and lower ranges by age, as well as repeatability coefficients. This was done through ANOVA-based procedures that extend standard repeatability assessment methods. Normative data tables are presented, with measures of repeatability for the various sites and modalities. For the conventional test range, reaching 55 degrees C, measurement of heat pain thresholds can define both hyper- and hypoalgesia. Application of repeatability coefficients allows for intra-individual inter-session comparison in longitudinal studies.

Adult↗

Sweat secretion, stratum corneum hydration, small nerve function and pruritus in patients with advanced chronic renal failure.

Sweat secretion, stratum corneum hydration and small nerve fibre function were measured in 40 patients with advanced chronic renal failure (CRF), using pilocarpine iontophoresis, electrical capacitance and a thermal sensory analyser which measures the thresholds of warm and heat pain sensation. Correlations were sought between these parameters, and the presence and severity of pruritus and skin xerosis were compared with 45 healthy control subjects. The mean sweat secretion and stratum corneum hydration of CRF patients were significantly lower than in controls. Thirteen patients had pathological thresholds to warm sensation on the foot, and eight on the hand. None had pathological thresholds to heat-pain. The presence of pruritus did not correlate with any of the following: xerosis, stratum corneum hydration, sweat secretion or the results of thermal testing.

Aged↗

Corpus cavernosum electromyogram: spontaneous and evoked electrical activities.

Sympathetic skin responses recorded from the surfaces of limbs and the penis resemble the waveforms recorded by needle from the corpora cavernosa. Thus, corpus cavernosum electromyography might reflect a systemic sympathetic response rather than unique smooth muscle corporeal activity. We recorded electrical activity simultaneously from the corpora and limbs of 10 subjects. Spontaneous activity was unique to the corpora, while electrical activity in response to sympathetic activating maneuvers was found simultaneously in the corpora and limbs (Fisher's exact test, p < 0.001). It is concluded that 2 types of electrical activity can be recorded from the corpora--spontaneous activity, which might reflect specific smooth muscle activity, and response activity, which is part of the systemic response to sympathetic stimulation.

Adult↗

Full dose vincristine (without 2-mg dose limit) in the treatment of lymphomas.

BACKGROUND: Most current lymphoma protocols limit vincristine dose to 2 mg per single dose. Because a lower dose of vincristine may be associated with poorer outcome, there is some rationale to increase the dose of vincristine. METHODS: The feasibility of full dose vincristine (i.e., 1.4 mg/m2 without 2-mg dose limit) was prospectively evaluated in lymphoma patients treated with various combinations. After an initial dose of 1.4 mg/m2, patients were carefully monitored, and dose was modified according to toxicity. RESULTS: One hundred and four consecutive patients (31 with Hodgkin's disease and 73 with non-Hodgkin's lymphoma), aged 18-78 years were evaluated. The first dose was greater than 2 mg in 90% of the patients. The mean actual dose (percent of projected dose) was 100% in the first course and gradually decreased to 64% in the eighth course. The mean actual dose intensity of vincristine (percent of projected dose intensity) during the initial six cycles of prednisone, methotrexate, calcium leucovorin, doxorubicin, cyclophosphamide, etoposide, and mechlorethamine, vincristine, procarbazine, prednisone (ProMACE/MOPP), cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and MOPP/doxorubicin, bleomycin, and vinblastine (MOPP/ABV) was 82% and MOPP/doxorubicin, bleomycin, and vinblastine was 82%, 83%, and 87%, respectively. Symptoms of neuropathy developed in 92% of the patients and were usually of mild or moderate severity. Toxicity included World Health Organization (WHO) Grades 3 and 4 constipation in 10 (10%), and WHO Grade 3 peripheral neurotoxicity in 16 (15%) patients. Rapid improvement was usually noticed within a few weeks after withdrawal of vincristine. The median duration of symptoms from discontinuation of vincristine was 3 months for paresthesiae and motor weakness and 5 months for muscle cramps. CONCLUSIONS: Full dose vincristine in lymphoma protocols is feasible but is associated with increased toxicity. The therapeutic advantage of full dose vincristine has yet to be proven.

Adolescent↗

Variance of sensory threshold measurements: discrimination of feigners from trustworthy performers.

Sensory threshold measurements are criticized as subjective and therefore not to be relied upon in clinical diagnostic practice, particularly when deliberate deception by the patient is suspected. In an attempt to devise a method which permits dependable sensory threshold interpretation, individual variability of thresholds was examined in normal and neuropathic subjects. Normals were also instructed to feign sensory impairment resulting from hypothetical injury. For each subject, a number of threshold readings were averaged, yielding individual means and variances. Feigning normal subjects evidenced a larger variance compared to trustworthy normal and neuropathic subjects. Thus, alertness to variance reinforces the psychophysical analysis: small variance values suggest trustworthy normal or pathological results, whereas large variance calls the interpreter's attention to feigned results or inattentive test performance.

Cold Temperature↗

Thermal testing: normative data and repeatability for various test algorithms.

Measurement of thresholds for warm and cold sensation was performed on 106 normal subjects, at thenar eminence and foot dorsum. Three test algorithms were used, the reaction-time-inclusive method of limits, and reaction-time-exclusive methods of levels and staircase. Tests were repeated 2 weeks following the first for most of the subjects, and after elimination of 5 outlying subject data points, and determination of no systematic relationship between magnitude and variability of test scores, data from between 72 and 76 subjects were used to derive repeatability coefficients, by ANOVA-based procedures which extend standard repeatability assessment methods. Normative data tables are presented, with measures of repeatability for the various algorithms and modalities. Method of limits tests exhibited inter-session bias, and large repeatability coefficients, compared with methods of levels and staircase, which exhibited no bias and had better (lower) repeatability coefficients. All three methods had similar test durations. We conclude that on the basis of these data, the reaction-time-exclusive methods of levels and staircase have a definite advantage over the method of limits.

Adult↗

The triple cold syndrome. Cold hyperalgesia, cold hypoaesthesia and cold skin in peripheral nerve disease.

A syndrome of cold hyperalgesia associated with cold hypoaesthesia is described in 28 patients with peripheral polyneuropathy or mononeuropathy of various aetiologies. A mechanism of sensory disinhibition, where diminished cold-specific A delta input releases cold pain input carried by C nociceptors, is proposed to explain the hyperalgesia. In most patients, the symptomatic skin is abnormally cold. This is a likely consequence of vasospasm, due to sympathetic denervation supersensitivity, caused by dropout of sympathetic efferents as part of the small caliber nerve fibre insult. The term 'triple cold syndrome' is coined to describe this specific pathophysiological condition. Descriptively it is a mirror image of erythralgia, as described by Sir Thomas Lewis (1936) and updated by one of the present authors, a human condition also centred around anomalous primary nociceptor input, in which there is heat hyperalgesia and hot symptomatic skin due to C nociceptor sensitization and vasodilatation from antidromic discharge. Thus, like the latter condition, the triple cold syndrome emerges as an independent clinical entity with definable abnormal mechanisms which should be retrieved out of the all-embracing, descriptive, diagnostic category 'reflex sympathetic dystrophy--causalgia'.

Adult↗

Bladder sensory power factor (BSPF): a novel diagnostic tool.

A simple clinical test for assessment of sensory function of the urinary bladder is described. It is performed during urodynamic assessment, consisting of stepwise filling of the bladder by gas. Subjects give numerical description of the perceived magnitude of pressure at each step, using an open-ended ratio scale. Based on Stevens law of psychophysics, the bladder sensory power factor (BSPF) is extracted from these data, reflecting the sensory state of the bladder. A BSPF of 1.01 +/- 0.12 (mean +/- SD) was found for 13 normal subjects. For 20 patients with lower urinary tract complaints who had a lesion of lumbosacral nerve roots, the BSPF was 0.59 +/- 0.23 (P < 0.001, t-test). In 16 (80%) of them BSPF was lower than 0.77 (= normal mean -2 SDs), being markedly more sensitive than the punctual sensory parameters-bladder sensory threshold (25%) or capacity (35%). BSPF is presented as a sensitive and easy to perform test for assessment of the sensory function of the human urinary bladder.

Adult↗

Mechanical hyperalgesias in neuropathic pain patients: dynamic and static subtypes.

Two behavioral kinds of mechanical hyperalgesia can be clearly discerned by clinical criteria in patients with neuropathic syndromes, i.e., a dynamic type, elicitable by lightly stroking the symptomatic skin, and a static type, elicitable by steadily applying gentle pressure on it. Of 28 patients studied, 19 had dynamic and 18 had static type mechanical hyperalgesia (9 expressed both types). Experimental compression-ischemia nerve block totally abolished the dynamic hyperalgesia in all patients except in 2, in whom it was markedly diminished. Disappearance of dynamic hyperalgesia occurred contemporaneously with block of myelinated A fibers, as expressed by abolition of the sensations of touch and cold, monitored quantitatively. Static hyperalgesia, however, outlasted A-fiber block in 15 of 18 patients; the phenomenon persisted during the stage when only unmyelinated fibers were available for impulse conduction. It is thus concluded that, at the primary afferent level, dynamic hyperalgesia is mediated by myelinated fibers, whereas static hyperalgesia depends on unmyelinated afferents. These two kinds of hyperalgesia represent discrete pathophysiological entities with distinct clinical connotations.

Adult↗

Single C nociceptor responses and psychophysical parameters of evoked pain: effect of rate of rise of heat stimuli in humans.

1. Effects of rate of rise of temperature stimuli applied to skin on (i) unitary receptor threshold and frequency response often single C nociceptors, and (ii) on magnitude and reaction times of evoked pain were studied in fifteen healthy human volunteers. 2. Temperature ramps of 32 to 45 or 47 degrees C were applied at three consistent rates of rise to receptive fields of C nociceptors in dorsum of foot (n = 9) or hand (n = 1). For rates of rise of 0.3, 2.0 and 6.0 degrees C/s, mean receptor threshold for heat was remarkably uniform: 41.5 +/- 0.57, 41.5 +/- 0.61 and 41.9 +/- 0.71 degrees C respectively. 3. The mean discharge rate of the ten cutaneous C nociceptors increased with rate of rise of temperature stimuli: 1.22 +/- 0.13, 4.57 +/- 0.49 and 13.45 +/- 0.71 impulses/s, respectively, for stimulus temperature rates of 0.3, 2.0 and 6.0 degrees C/s. 4. Magnitude estimates of pain for thirteen subjects also increased with rate of rise of temperature stimuli. Mean normalized magnitude estimates of heat pain were: 11.8 +/- 1.55, 15.1 +/- 0.84 and 28.0 +/- 1.87 for stimulus rates of rise of 0.3, 2.0 and 6.0 degrees C/s, respectively. 5. Results of simultaneous recordings of reaction time for pain and of C nociceptor responses to heat ramps given at 2.0 degrees C/s, in three subjects, indicate that under those circumstances heat pain messages are exclusively mediated by C nociceptors.

Adult↗

Differential effect of compression-ischaemia block on warm sensation and heat-induced pain.

The effect of compression-ischaemia nerve block on psychophysical thresholds for warm sensation and heat-induced pain was studied on 19 normal human volunteers. Although those two sensory submodalities should be predicted to block simultaneously, based on the fact that both are served by unmyelinated primary afferents, it was actually found that warm sensation was much more vulnerable to compression-ischaemia than heat-induced pain. This is interpreted as resulting from different summation requirements for each of the two sensory modalities; sensation of warmth depends on spatial summation to a larger extent than heat-induced pain. Such differential vulnerability is in line with recent clinical studies reporting deterioration of warm sensation associated with preservation of heat pain in peripheral nerve disorders caused by diabetes, ageing and other neuropathic processes.

Afferent Pathways↗

Warm and cold specific somatosensory systems. Psychophysical thresholds, reaction times and peripheral conduction velocities.

Perception thresholds for warm and cold sensation were measured by two methods, the method of levels and the method of limits, at various rates of temperature change. The following findings were obtained. (1) The threshold value is critically dependent upon the method through which it is obtained, being higher for the method that includes reaction time in the measurement. (2) When using a method that includes participation of reaction time, threshold increases with increasing rate of temperature change. (3) The artefactual threshold elevation recorded through the method of limits corresponds precisely to the reaction time. (4) Conduction velocities for the primary afferents mediating the sensations of warm and cold, calculated on the basis of reaction time and conduction distance are in keeping with the mediation of warm sensation by unmyelinated primary afferents and of cold sensation by small myelinated afferents. (5) Measurement of threshold by the method of levels and direct measurement of reaction time enables calculation of conduction velocity for the specific sensory submodality tested from a single stimulation site.

Adolescent↗

Release of cold-induced burning pain by block of cold-specific afferent input.

While the pure sensation of cold is evoked by activation of a specific set of afferent channels, an additional set is believed to be activated by noxious low-temperature stimuli evoking cold pain. At primary afferent level, the channels concerned with the cold fraction of cold pain are served by myelinated A delta cold-specific fibres, whereas those concerned with the pain fraction are served by unmyelinated C nociceptors. In the present study, interaction between the two types of afferent input underlying cold pain was investigated by selectively blocking conduction in myelinated fibres. When doing so to the point of abolishing cold sensation, ramps of low-temperature stimuli eventually evoked a first sensation of burning pain. In addition to, and contemporaneous with, this change in quality, a significant decrease in pain threshold (reduction in required stimulus energy) was recorded when applying a noxious low-temperature stimulus. Such exaggeration in magnitude of low temperature-induced pain and the unmasking of its burning quality by A fibre block imply release of central sensory transmission due to removal of inhibitory primary afferent input. Myelinated fibres transmitting either tactile, cold sensations or both could exert this inhibition. Previous evidence of suppression of pain by low-temperature stimuli indicates that it is the cold-specific input that normally exerts this central gating on nociceptor input. The present results may also offer an explanation for the occurrence of a syndrome of burning pain on cold exposure in neuropathic patients with impaired ability to perceive cold.

Adult↗