How does antibody combination really predict IDDM in the general population? Fortune telling--not fortune spending.
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Autoantibodies↗
Biomedical subjects
E Sprecher
Publications and source records attributed to E Sprecher.
D-penicillamine-induced pancreatic islet autoantibody production is independent of the immunogenetic background: a lesson from patients with Wilson's disease.
D-penicillamine (d-PA) was reported to induce various immunological abnormalities including production of autoantibodies to insulin. These abnormalities were mainly described in patients with primary immunological disorders such as rheumatoid arthritis. In order to clarify whether d-PA-induced immune disorders are restricted to patients genetically prone to develop autoimmune diseases or to a direct drug effect, we tested for the presence of various autoantibodies and for molecular HLA typing in 17 patients with Wilson's disease treated with this drug. In 2/17 patients, low-titer (10 JDFU) circulating islet cell autoantibodies (ICA) were detected, while another patient was positive for the presence of insulin autoantibodies. None of the sera tested showed reactivity for glutamic acid decarboxylase or ICA512. Five of twelve patients were positive for anti-single-stranded DNA autoantibody. Molecular HLA typing of the autoantibody-positive subjects showed that they carry HLA haplotypes not associated with insulin-dependent diabetes. The insulin response to intravenous glucose tolerance test in two patients with autoantibodies was found to be normal. A second blood testing of the autoantibody-positive patients 5 months following initial evaluation revealed conversion to negativity in all three. Our results suggest that d-PA-induced autoantibodies in patients with Wilson's disease are independent of the immunogenetic background characteristics of diabetes.
Adolescent↗
The reduced folate carrier (RFC-1) gene is expressed in the murine epidermis.
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Animals↗
Reduced folate carrier (RFC-1) gene expression in normal and psoriatic skin.
Methotrexate is widely used in the treatment of severe psoriasis. However, little is currently known about the mechanisms underlying its therapeutic activity in the skin. Methotrexate has been shown to be carried into cells through the reduced folate carrier (RFC-1). The recent cloning and characterization of the human gene encoding this transmembranal carrier enabled us to investigate RFC-1 gene expression in human skin. Biopsies were obtained from the skin of healthy and psoriatic volunteers. RNA extracted from these biopsies was analyzed by the reverse transcriptase-polymerase chain reaction technique. While RFC-1 gene expression was barely detectable in the uninvolved skin of psoriatic patients and in the skin of healthy volunteers, high levels of RFC-1 transcripts were found in biopsies obtained from psoriatic plaques. To further investigate this pattern of gene expression, we studied skin biopsies by in situ hybridization with a labeled antisense riboprobe specific for the RFC-1 gene. The RFC-1 gene was found to be weakly expressed in the epidermis, in biopsies obtained from the skin of healthy subjects as well as in those from the uninvolved skin of psoriatic patients. In contrast, in biopsies obtained from psoriatic plaques, high levels of RFC-1 gene transcripts were found mostly in the spinous layer of the epidermis. These results suggest the existence of a specific methotrexate carrier in the human epidermis, and may bear relevance to the cutaneous manifestations of methotrexate toxicity.
Adult↗
P300 and stress in mild head injury patients.
OBJECTIVE: The P300 component of event-related potentials is affected by personal meaningfulness of the stimulus to the subject. Thus, the P300 component could provide an objective parameter in the emotional assessment of road accident mild head injury patients, when exposed to relevant stimuli. METHODS: Thirteen patients with post-traumatic symptoms and 14 healthy controls were evaluated in this study. Two word types, distinguished by color, were presented on a computer screen in active 'oddball' paradigm conditions. In the first subtest, the targets were accident-related (stressful) words; in the second subtest, the targets were non-accident-related (neutral) words. Target (20%) and non-target (80%) were defined by word color. Data recorded from Pz were analyzed for P300 parameters. RESULTS: Patients and controls differed in their reaction to word types (group x word main effect P = 0.0089), regardless of the oddball presentation. Overall, accident-related words produced a significantly larger P300 wave than neutral words in patients (P = 0.0001), but not in controls (P = 0.5741). Significant correlation was found between combined P300 amplitude difference (all stressful words vs. all neutral words) and the patient's Zung state anxiety score (r = 0.68, P = 0.01). CONCLUSION: We suggest the P300 component can provide a useful, objective tool in the assessment of mild head injury patients.
Accidents, Traffic↗
HLA class II immunogenetics of IDDM in Yemenite Jews.
The association between HLA-DR and DQ and insulin dependent diabetes mellitus (IDDM) was analyzed in 47 patients and 76 controls of Yemenite Jewish origin. The IDDM susceptibility alleles DRB1*03011, DQA1*0501, DQB1*02 and DRB1*0402, DQA1*0301, DQB1*0302 found in Caucasians had a very strong predisposing effect also in the Yemenite IDDM group. The DRB1*07, DQA1*0201 and DQB1*02 alleles were found to have a strong negative association with IDDM. None of the patients carried DRB1*07 and DQA1*0201 compared with healthy controls (43.7%). Our analysis revealed that the DRB1*03011 DQA1*0501 DQB1*02/DRB1*04 DQA1*03 DQB1*0302 heterozygous genotype confers the highest susceptibility (59.6% in patients vs. 0% in controls). The homozygous DRB1*03 and DRB1*04 genotypes were also found to be positively associated with the disease. 81% of the patients compared to 1.3% of controls carried the susceptibility alleles on both haplotypes. In conclusion, the development of IDDM in Yemenite Jews is strongly dependent on the presence of the susceptibility HLA alleles and on the absence of the DRB1*07 haplotype. The Yemenite Jewish group is uniquely homogenous with regard to genetic susceptibility factors involved in the process of IDDM, and may thus be an ideal model for further genetic studies.
Alleles↗
Standard and low-dose short adrenocorticotropin test compared with insulin-induced hypoglycemia for assessment of the hypothalamic-pituitary-adrenal axis in children with idiopathic multiple pituitary hormone deficiencies.
Insulin-induced hypoglycemia (IIH) is the gold standard test for assessment of the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, but it may be hazardous. We sought to determine whether the standard (250 micrograms) or low-dose (1 microgram/1.73 m2) short ACTH test can replace IIH in patients with idiopathic multiple pituitary hormone deficiencies (MPHD). Three groups of subjects were studied: 1) control group, children with early or accelerated puberty and no other evidence of adrenal or pituitary pathology (n = 13, age 10.1 +/- 2.2 yr, 3 males); 2) patients with idiopathic hypothalamic pituitary insufficiency and either isolated GH deficiency or MPHD and preserved HPA function (n = 20, age 13.7 +/- 4.4 yr, 13 males); and 3) MPHD patients with impaired HPA axis function (n = 10, age 16.8 +/- 4.8 yr, 9 males). IIH and the 250 micrograms and 1 microgram/1.73 m2 ACTH tests were performed in groups 2 and 3; group 1 underwent only the ACTH tests. Pass peak cortisol level was defined as 520 nmol/L. No significant difference was noted between the standard and low-dose tests in the 30-min cortisol response to ACTH. Basal and peak cortisol levels attained on both ACTH tests were similar in groups 1 and 2 and significantly lower in group 3 (P < 0.0001). Both the 250 and 1 microgram ACTH tests were highly correlated with IIH (r = 0.71, P < 0.0001 for the 250 micrograms, r = 0.7, P < 0.0001 for the 1 microgram, n = 30), and both demonstrated high sensitivity (90% each) and specificity (100% and 90%, respectively) compared with IIH. We conclude that in idiopathic MPHD patients, both the standard and low-dose ACTH tests are equivalent to IIH in detecting HPA insufficiency. We suggest that they can replace IIH as a screening test for the integrity of the HPA axis in children with suspected MPHD.
Adolescent↗
The prevalence of cutaneous manifestations in IDDM patients and their association with diabetes risk factors and microvascular complications.
OBJECTIVE: The aim of our study was to evaluate the frequency of skin manifestations, including the diabetic hand syndrome, in young IDDM patients. In addition, we studied the relation of the cutaneous manifestations to diabetes duration, glycemic control, and microvascular complications. RESEARCH DESIGN AND METHODS: The frequency of skin manifestations, including the diabetic hand syndrome, were examined in 238 IDDM patients (disease duration > 5 years) and 122 healthy control subjects in a cross-sectional study. In addition, we studied the relation of the cutaneous manifestations with diabetes duration, glycemic control, BMI, microvascular complications, and stratum corneum hydration using a stepwise logistic regression. RESULTS: Diabetic skin manifestations were detected in 168 of 238 (71%) IDDM patients and in 18 of 122 (14%) of the control subjects. Ichthyosiform skin changes of the shins, scleroderma-like skin changes, tinea pedis, and dry scaly palms were detected in 48 vs. 7%, 39 vs. 0%, 32 vs. 7%, and 21 vs. 0.8% of the patients and control subjects, respectively. In the diabetic patients, a significant association was found between ichthyosis of the shins and scleroderma-like skin changes of the hand (P < 0.001) and between scleroderma-like skin changes and the skin dryness of the palms (P < 0.0001). When diabetic risk factors were considered, diabetes duration was significantly associated with scleroderma-like skin changes and ichthyosis of the shins (P < 0.0001). The latter was also found to be related to diabetic retinopathy (P < 0.0001). Keratosis pilaris was present in 21% of the patients versus 9% in control subjects and was found to be exclusively associated with high BMI. CONCLUSIONS: Acquired ichthyosis is a common finding and the most prevalent skin manifestation in young IDDM patients. The development of several skin manifestations in insulin-dependent patients seems to be related to duration of diabetes and to development of diabetic microvascular complications.
Adolescent↗
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↗