[Immune phenomena in liver diseases].
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Biomedical subjects
Publications and source records attributed to R Klein.
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In sera from patients with different forms of inner ear diseases antibodies against endoplasmic reticulum (anti-ER) could be detected by ELISA in association with antisarcolemmal (ASA) and antiendothelial antibodies (AEA). 36% of 296 patients with sensorineural hearing loss (SNHL), 30% of 20 patients with tinnitus, 21% of 48 patients with sudden deafness and 20% of 49 patients with Menière's disease had ASA. 94% of these ASA positive patients were also positive for anti-ER. The overall frequency of anti-ER was 57% of patients with SNHL, 60% of patients with tinnitus, 46% of patients with sudden deafness and 22% of patients with Menière's disease. Analysing the clinical course in 5 anti-ER positive and 11 anti-ER negative patients with SNHL it was shown that all 5 patients either had a progressive course and/or a systemic manifestation in contrast to only 4 of the anti-ER negative patients. Anti-ER antibodies were also detected in 38-53% of patients with different chronic inflammatory disorders of unknown aetiology (polymyalgia rheumatica, vasculitis, sarcoidosis, ankylosing spondylitis etc.) while only 6% of patients with typical autoimmune disorders (collagen diseases, lupoid hepatitis, primary biliary cirrhosis) and 8% of blood donors had this antibody. Therefore it can be concluded that anti-ER antibodies have no apparent relevance for the diagnosis of SNHL. They may be, however, indicative of a secondary autoimmune process triggered by a persistent infectious agent.
The specificity and clinical relevance of nine antimitochondrial antibodies (AMA) - anti-M1 to anti-M9 - are described. All nine AMA types react with antigens which are associated either with inner (M1, M2, M7) our outer mitochondrial membranes (M3, M4, M5, M6, M8, M9) derived from rat liver or beef heart mitochondria. These antigens can be clearly distinguished by their different physical and chemical properties. Anti-M1 to anti-M9 can be related to distinct clinical entities: anti-M1, anti-M5, and anti-M7 are found in nonhepatic disorders, such as syphilis (anti-M1), undefined collagen diseases (anti-M5), and some forms of cardiac diseases (anti-M7). Anti-M3 and anti-M6 are detected in drug-induced disorders, such as phenopyrazon-induced pseudolupus syndrome (PLE; anti-M3) and iproniazid-induced hepatitis (anti-M6). Anti-M2, anti-M4, anti-M8, and anti-M9 are confined to primary biliary cirrhosis (PBC). Anti-M2 is a specific marker for the diagnosis of PBC; 96% of PBC patients (n = 752) were anti-M2 positive. Anti-M4 and anti-M8 seem to reflect disease activity. Anti-M9 antibodies occur preferentially in early PBC. The clinical course of PBC was analyzed with respect to four different AMA profiles: profile A: only anti-M9 positive in the ELISA; profile B: anti-M9 and anti-M2 positive in the ELISA; profile C: anti-M2 positive in ELISA and complement fixation test (CFT), but anti-M4 and anti-M8 positive only in the ELISA; and profile D: anti-M2, anti-M4, anti-M8 positive in ELISA and CFT. Patients with profile A and B were found to have a rather benign course while those patients with profile C and D showed a rather progressive course when followed over a period of 6-15 years. Considering the similarities between bacterial and mitochondrial membranes, it is suggested that the formation of AMA of different specificities in PBC, especially of the anti-M2 type, may be induced by cross-reacting antigens.
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The latency of the cortical SEP (CSEP) following stimulation of the posterior tibial nerve is nearly always shorter than the latency of the CSEP evoked by stimulation of the sural nerve. Till now this fact was believed to be due mainly to different conduction velocities within the peripheral nerves owing to the muscle afferents of the posterior tibial nerve. The surprising discovery that the lumbar and cervical SEPs exhibit much shorter time lags than the CSEPs led to the experiments described in this paper: during the registration of the peripheral sciatic nerve action potentials only slight differences in the conduction velocities were observed. Thereupon a topographical analysis was performed during which the minimum latency of the sural nerve CSEP was not measured at the usual C'z electrode position but was found to be shifted to a more occipital and ipsilateral point. From these results it was concluded that, for the main part, the latency difference of the CSEPs results from 'central factors,' which had already been postulated for the median nerve CSEP by Burke and coworkers.
Recent studies of the nasal cycle and forced uni-nostril breathing have demonstrated that integrated EEG amplitudes are greater over the hemisphere contralateral to the dominant (less congested) or unblocked nostril. Two experiments were designed to determine if asymmetries in nasal airflow, occurring naturally as a result of the nasal cycle or artificially as a result of forced uni-nostril breathing have consequences for human performance on verbal and spatial tasks that are preferentially performed by the left and right hemispheres respectively. A significant relationship was obtained between the pattern of nasal airflow with normal breathing and relative spatial vs verbal performance. Forced uni-nostril breathing had no effect on performance.
The purpose of this report is to present a system for grading the severity of diabetic retinopathy that is a rapid, relatively inexpensive, and standardized alternative to the more detailed Early Treatment Diabetic Retinopathy Study (ETDRS) system; present data on its reproducibility; and compare it to the detailed ETDRS grading system. The alternative system was used to grade fundus photographs obtained during a large prevalence study, the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). The alternative method involved grading seven stereoscopic standard fields as a whole, and assigning a level of severity for the eye according to the greatest degree of retinopathy using a modified Airlie House Classification scheme. Using an eight-level classification system of increasing severity of retinopathy, there was 78.3% exact agreement between the alternative and ETDRS systems. A grader regraded all 503 disagreements, and was in exact agreement 49.3% of the time with the alternative system, 35.7% of the time with the detailed system, and 15.0% with neither the alternative or detailed systems. Interobserver agreement for the alternative system was 78.5%; intraobserver agreement over a 9 month to 1 year period was 90.0% for grader 1 and 84.0% for grader 2. The alternative system of grading, when used by experienced graders, is a reproducible method for objectively determining retinopathy status in epidemiologic studies.
The authors present five cases of severe retinal ischemia associated with gentamicin injection. In three of the cases massive doses of gentamicin were erroneously injected into the eye; in two of the cases the authors presume that gentamicin toxicity occurred. The sequence of clinical findings was similar in all five cases. The prominent findings included early superficial and intraretinal hemorrhages, opaque and edematous retina, cotton-wool infarcts, arteriolar narrowing, and venous beading. Fluorescein angiography revealed severe retinal vascular nonperfusion. Chronic findings included rubeosis irides, neovascular glaucoma, retinal pigmentary degeneration, and optic atrophy. Of the documented cases of massive intraocular gentamicin injection, two patients had no light perception (NLP) vision and one had bare light perception. Of the two cases of presumed gentamicin toxicity, one had 20/400 vision and one had count fingers vision. Strict precautions are necessary to prevent the catastrophic events resulting from inadvertent gentamicin injection; such precautions should include precise labeling of all injectable solutions on the surgical field, waiting to draw up injectable antibiotics until the time they are needed, and drawing up injectable antibiotics under direct physician observation. All intravitreal injections should be performed slowly, in the anterior vitreous, with the needle bevel up.
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This report presents the results of a comparison between information obtained from response to the question "Have you been told that the diabetes has affected the back of your eyes, that is, the retina?" and the determination of the severity of retinopathy by grading of stereoscopic fundus photographs. Both "younger onset" (n = 996) and "older onset" (n = 1,370) persons who participated in a large population-based study of diabetic persons in southern Wisconsin from 1980-1982 were included. For the younger onset persons, 31.1% responded positively, while 70.7% were found to have retinopathy. The sensitivity of the questionnaire response varied from 17.8% for persons with mild nonproliferative retinopathy to 81.9% for persons with proliferative retinopathy. The specificity was 97.3%. For the older onset persons, 14.9% responded positively, while 54.2% were found to have retinopathy. The sensitivity of the question varied from 9.9% for persons with mild nonproliferative retinopathy to 68.7% for persons with proliferative retinopathy. The specificity was 93.3%. The question used in this survey provides a highly specific measure of prevalence; it is most sensitive for proliferative retinopathy.
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The state dilemma of American medical care is rapidly increasing costs that threaten both quality of care and equal access to care. A frequently cited example of what the United States can expect as the crunch between cost and care gets worse is rationing, as used in the British National Health Service. The introduction of the British National Health Service, according to this analysis, is inappropriate and clouds the relevant issues. The example of national health insurance in Canada--a country much more similar to the United States in size, geography, and governmental and social structure--is a much more appropriate model to examine. Canada, comparably large, wealthy, and socially heterogeneous, spends approximately 20% less of its GNP on medicine, yet has both universal national health insurance and no serious rationing problem. Their example is reason to question the stark dilemma of cost vs. care in American medicine.
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In 22 of 45 patients with chronic cholestatic liver inflammation and humoral immune phenomena, followed over 15 years with at least one liver biopsy, there was the histological picture of primary biliary cirrhosis (PBC), stages I to IV, with constantly demonstrable antimitochondrial antibodies (AMA) of M2-type. In 12 patients there were signs of PBC and chronic active hepatitis (CAH) in the liver histology, and they were M2-positive. Six of them also had M4-antibodies and were thus classified as 'mixed form'. The other six were seropositive for liver-membrane antibodies (LMA) and (or) antinuclear antibodies (ANA) and thus demonstrated an overlap between PBC and autoimmune or lupoid CAH. In five patients there was autoimmune CAH of lupoid type, in four of them with LMA or ANA without M2- or M4-antibodies. The remaining six patients had pericholangitis with persisting ANA and increased serum concentrations of immunoglobulin M without M2- and M4-antibodies, as well as LMA. Clinically a nondestructive polyarthritis predominated without definite signs of collagenosis. The listed immunoserological parameters make it largely possible to differentiate classical PBC, mixed forms or overlap of PBC and CAH, autoimmune CAH and nonpurulent cholangitis of pericholangitic type.
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