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E Sprecher

Publications and source records attributed to E Sprecher.

At least 19 recordsLinked to original sources

Vibration reduces thermal pain in adjacent dermatomes.

Spatial summation of thermal pain crosses dermatomal boundaries. In this study we examined whether a vibrational stimulus applied to adjacent or remote dermatomes affects thermal pain perception to the volar forearm. Contact heat at 2 degrees C above thermal pain threshold was applied, and a Visual Analog Scale (VAS) was used for pain assessment. We found a significant decrease in mean VAS rating when simultaneous vibratory stimuli were given to the dermatome adjacent to that receiving thermal stimulation, or to the same dermatome on the contralateral side. There was no change in VAS rating when vibration was given two or more dermatomes away. Vibration within the same dermatome also did not yield a significant change in VAS rating, possibly due to difficulty in magnitude assessment of stimuli given simultaneously within a single dermatome. The finding that vibration can reduce pain across dermatomes may allow for more flexible design of stimulation therapy for pain.

Adolescent

Non-classical 21-hydroxylase deficiency in infancy and childhood: the effect of time of initiation of therapy on puberty and final height.

OBJECTIVE: To review the characteristics of children with non-classical 21-hydroxylase deficiency (NC-21-OHD) diagnosed during infancy and childhood, and to evaluate the relationship of pubertal and bone age maturation at initiation of glucocorticoid therapy with the course of puberty and final height. DESIGN: We retrospectively compared the course of puberty, growth pattern and final height in two groups of patients: group A (two males, six females), hydrocortisone (HC) treatment 7.5-15 mg/m2 per 24 h, initiated > or = 1 year before onset of true puberty and group B (seven females), treatment started with the first signs of true puberty present. PARTICIPANTS: Thirteen girls and two boys with NC-21-OHD diagnosed at age range 0.5-10.6 years were followed-up for 9.0 +/- 3.8 years (mean +/- S.D). Therapy with HC was initiated because of signs of hyperandrogenism, accelerated growth and bone maturation, or true precocious puberty. The HC dose was adjusted according to linear growth and basal plasma androgen levels. RESULTS: Puberty and peak height velocity developed significantly earlier in the girls of group B: gonadarche at 7.9 +/- 1.4 years and peak height velocity at 9.2 +/- 1.4 years vs 10.2 +/- 0.4 years (P = 0.002) and 11.5 +/- 0.7 years (P = 0.006) in group A. Menarche, however, occurred only slightly earlier in group B (12.0 +/- 1.1 vs 12.8 +/- 0.5 years, P = 0.068). All eight children in group A achieved a final height within the range of their mean parental height standard deviation scores (SDS) in comparison with only 1/7 in group B (P = 0.0014). Seven of eight patients who started therapy before a bone age of 9 years achieved a final height within the parental height SDS range, compared with 2/7 who started therapy later (P = 0.041). The final height SDS was significantly better for group A (0.05 +/- 0.19, mean +/- S.E.M.) than group B (-1.63 +/- 0.23, P = 0.0007), even when adjusted for a significant effect of the mean parental height SDS (A. -0.63 +/- 0.28; B, -0.89 +/- 0.31, P = 0.0245, ANCOVA). CONCLUSION: Every child with signs of excess androgen activity or early puberty should be studied for the possibility of NC-21-OHD. Screening programs for populations with a high frequency of the gene for NC-21-OHD would facilitate early diagnosis and treatment. Pubertal stage and bone age at the introduction of therapy dictate height prognosis. Initiation of therapy before puberty with careful follow-up and HC dose adjustment can assure the achievement of genetic adult height.

Adrenal Hyperplasia, Congenital

The P300 in pain evoked potentials.

Pain evoked potentials (EPs) have been used in the last two decades as means of obtaining objective measures of pain, in clinical and experimental setups. The possibility that the pain EP wave contains elements of the endogenous P300 potential rather than being a neurophysiological correlate of pain has been raised by a number of authors, but the issue has not been resolved. In this study, two experiments were performed to study the effect of nonmodality-specific factors on the laser EP: (1) a stimulus attend as opposed to a stimulus-ignore condition and (2) counterbalanced oddball and task P300 stimulus presentations. The latter was to permit full examination of the separate and combined influences of each condition on the EP. Stimuli were given to the radial hand of 10 healthy volunteers using a CO2 laser. The positive component of the laser EP was affected by both manipulations relating to (1) attention (P = 0.0146) and (2) the frequency condition (P = 0.003) in the P300 paradigm. The task condition in the second paradigm did not affect the positive wave on its own, although its effect was visible in interaction with frequency (P = 0.033). In conclusion, although the presence of a somatic component in the laser EP cannot be rules out, we suggest that the laser EP contains a definite non-modality-specific P300 component, and is not a pure neurophysiological correlate of pain intensity.

Acoustic Stimulation

Multiple session experimental pain measurement.

Experimental heat pain transients were administered to 30 normal volunteers over four weekly sessions, measuring both heat pain (HP) threshold and suprathreshold magnitude estimation through VAS. Repeatability and bias for these two factors were evaluated. Heat pain thresholds measured through the method of limits were previously shown to have inter-session bias, presumably due to a practice effect. Existence of such a bias between first and second measurement sessions casts doubt on the usefulness of this parameter for pain assessment of individuals over time. In the present study, measurements of normal HP thresholds over four sessions showed that bias exists between the first and successive sessions, but not among sessions other than the first. It is concluded that (i) HP thresholds obtained from a single session are of limited value, and should be carefully interpreted. (ii) Long-term studies that use the HP threshold should take results from the second (or later) session as their baseline. The Visual Analog Scale (VAS) is considered the 'gold standard' for assessment of clinical and suprathreshold experimental pain, and changes in VAS score are regarded as significant evidence of individual response to treatment, placebo, or experimental manipulation. Although its overall group accuracy and precision have been examined for both clinical and experimental pain, and found adequate (Price 1988), the VAS has not been rigorously assessed for repeatability. Stimuli at three pain levels, 1.5, 3 and 4.5 degrees C above each individual's heat pain threshold as determined at each session, were given. Several models of analysis of the VAS were tested and repeatabilities (r) obtained from these analyses demonstrate poor precision for each of the tested analysis models. For example, inter-session repeatabilities for the three individual pain levels ranged from r = 3.8-4.7, effectively providing a confidence interval of 7.6-9.4 for any VAS reading on a 0- to 10-point scale. An examination of intra-session VAS provided somewhat better results. Thus, use of the VAS in similar experimental settings is called into question. The use of the VAS in clinical settings, where individual assessments are necessary, is also called into question, but remains to be specifically tested.

Adolescent

Penile thermal sensation.

PURPOSE: To our knowledge no direct measurement of autonomic failure in the penis is currently available. Indirect techniques in clinical use, such as bulbocavernosus reflex, genital somatosensory evoked potentials and biothesiometry, all rely on large nerve fiber function. Since micturition and potency depend on small fibers of the peripheral system, tests of these fibers might be more relevant in the clinical diagnostic evaluation. We provide upper normal limits and demonstrate repeatability of small fiber mediated sensations of warm and cold sensory thresholds on penile skin. MATERIALS AND METHODS: Penile warm and cold sensory thresholds were measured in 35 healthy volunteers (at 2 sessions in 27) via 2 methods. RESULTS: Upper normal values, expressed as 95% confidence limits for warm and cold thresholds, through methods of limits and levels as well as inter-session repeatability are given. CONCLUSIONS: Penile thermal thresholds are repeatable and can be used as a valid diagnostic tool to assess somatic small fiber function in patients with lower urinary tract disorders.

Adult

Polyneuropathy in impotence.

Three hundred and forty-one consecutive impotent patients were evaluated for the presence of polyneuropathy (PNP) by neurophysiological and psychophysical tools, including nerve conduction and quantitative sensory tests (thermal and vibratory). PNP was present in 38% of diabetics, and 10% of non diabetics. Overall, PNP was found in 19% of impotent patients. PNP is relatively common among impotent patients, and might play a causative role. Patients judged 'neurogenic' and those judged 'vasculogenic', based on nocturnal tumescence test (NPT) and vasoactive drug injection tests, had very similar rates of PNP (21 and 23%, respectively). Thus it is suggested that the vasoactive drug injection test does not serve in discriminating neurogenic from non-neurogenic impotence. NPT, however, faithfully discriminates psychogenic from organic impotence, as far as PNP is involved, since a very low percentage of patients with normal NPT had PNP.

Adolescent

Pain-evoked potentials: what do they really measure?

Cerebral evoked potentials (EPs) in response to painful stimuli have been recorded since the 1970s. Based on the apparent relationship of the response amplitude to intensity of stimulation, these potentials are conventionally interpreted as reflecting the sensory-discriminative aspects of pain. As such, pain-EPs provide an objective measure for sensation of pain. An alternative interpretation regards the pain-EP as comprised of at least two overlapping components, one pain-specific, the other, a P300 wave. In the case of pain, the P300 may reflect the degree of discomfort or unpleasantness, thus reflecting the emotional-motivational aspect. To establish the nature of the pain-EP, mini doses of a benzodiazepine, counterbalanced with placebo, were given to 6 normal volunteers. Benzodiazepines decrease anxiety, and so diminish the emotional response to pain, but they have no analgesic effect. In all subjects, pain perception was unchanged, while the EP wave was almost completely obliterated. We conclude that the pain-EP reflects the emotional-motivational response to pain rather than the sensory-discriminative. Thus, it provides a useful neurophysiological tool for studying the emotions associated with pain.

Adult

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

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

Role of Langerhans cells and other dendritic cells in viral diseases.

Langerhans cells are part of a vast system of potent antigen-presenting cells known under the name of dendritic cells. During the last decade, much has been learned on dendritic cell involvement in the immune response to infectious diseases. This review briefly summarizes our current understanding of the role played by Langerhans cells and other dendritic cells in the pathogenesis of DNA and RNA virus infections. These data may form the basis for the development of innovative approaches in the diagnosis, prevention, and treatment of viral diseases.

Animals

Detection of IL-1 beta, TNF-alpha, and IL-6 gene transcription by the polymerase chain reaction in keratinocytes, Langerhans cells and peritoneal exudate cells during infection with herpes simplex virus-1.

Interleukin-1, tumour necrosis factor-alpha and interleukin-6 are considered to be major mediators of inflammatory processes. In the present study, cytokine gene transcription was detected by the polymerase chain reaction technique during cutaneous and intraperitoneal infection with herpes simplex virus-1. Epidermal cell suspensions obtained from mice infected with herpes simplex virus-1 in the ear pinna were enriched or depleted in Langerhans cells by immunomagnetic fractionation. Herpes simplex virus-1 infection in the skin was found to induce interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 gene transcription in keratinocytes at 24 hours post-infection. Gene transcription declined by 48 hours post-infection. Induction of interleukin-1 beta and tumour necrosis factor-alpha but not of IL-6 gene transcription was detected in Langerhans cells obtained from infected mice at 24 hours post-infection. In order to study cytokine gene transcription during intraperitoneal infection with herpes simplex virus-1, peritoneal exudate cells were obtained from infected mice. Maximal levels of interleukin-1 beta, tumour necrosis factor-alpha, and interleukin-6 mRNA were found in peritoneal exudate cells 6 hours after infection. RNA transcription declined at 24 hours post-infection and was no longer detectable at 48 hours post-infection. Since the higher susceptibility of newborn mice to intraperitoneal herpes simplex virus-1 infection has been suggested to be related to defective cytokine production, cytokine gene transcription was compared in peritoneal exudate cells obtained from infected newborn and adult mice. No significant differences in interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 gene expression were observed in peritoneal exudate cells obtained from newborn mice as compared with adult mice. In conclusion, cutaneous and intraperitoneal infection with herpes simplex virus-1 induces interleukin-1 beta, tumour necrosis factor-alpha and interleukin-6 gene transcription in epidermal and peritoneal exudate cells.

Animals

Interleukin-1 alpha gene-transcription in murine keratinocytes is inhibited by HSV-1 infection.

The effect of in vitro infection with herpes simplex virus 1 (HSV-1) on the Interleukin-1 (IL-1) activity of murine keratinocytes was investigated. IL-1 alpha mRNA synthesis was measured by the Northern blot technique, and the IL-1 protein production was measured in terms of the ability of dialysed supernatants from cultures of uninfected and HSV-1 infected keratinocytes to enhance mitogen-induced murine thymocyte proliferation. IL-1 alpha mRNA-synthesis in uninfected keratinocytes was detected 24 h and 48 h after isolation of the keratinocytes. IL-1 protein secretion by these keratinocytes was measureable at 18 h and reached a peak of 73 h, whereas intracellular and membrane-bound IL-1 protein production reached a maximum after 25 h. Keratinocytes, which had been cultured in vitro for 18 h, were infected with HSV-1 for 2 h and further cultured for an additional 4 h or 22 h before IL-1 measurements. A marked reduction of IL-1 alpha gene-expression was noted 6 hours after HSV-1-infection of keratinocytes, and nearly total shut-off was detected after infection for 24 h. Reduced gene-expression was paralleled by a reduction in the IL-1 protein secretion from the HSV-1 infected keratinocytes.

Animals

Effect of genetically determined immunodeficiency on epidermal dendritic cell populations in C57BL/6J mice.

Mice homozygous for three different recessive mutations known to cause pleiotropic defects in the immune system and in the skin were used to evaluate the relationship between the classical immune system and dendritic epidermal cell populations. Numbers of Langerhans cells (LCs) and Thy-1+ dendritic cells (Thy-1+DEC) were determined using indirect immunofluorescence microscopy of epidermal whole mounts taken from viable motheaten (mev), nude (nu), and rhino (rhhr) mice. All mutants were maintained on the C57BL/6J strain background and were compared with their respective littermate normal controls. Viable motheaten mice had normal numbers of LCs at 1 month of age. However, by 8 weeks of age, LC density had decreased threefold. Nude and rhino mice had normal numbers of LCs at all ages tested. There was no significant effect of the viable motheaten mutation on numbers of Thy-1+DEC. Although nude mice showed normal numbers of Thy-1+ DEC at 1 month of age, these athymic mice had a threefold decrease in numbers of such cells by 6 months. In contrast to the reduced numbers of Thy-1+DEC seen in nude mice, rhino mice showed a four- to fivefold increase in the numbers of these epidermal cells at all ages tested. These findings suggest new mouse models for investigating the development, regulation, and biological properties of epidermal dendritic cell populations.

Animals