Primary autonomic failure: three clinical presentations of one disease?
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Autonomic Nervous System Diseases↗
Biomedical subjects
H Kaufmann
Publications and source records attributed to H Kaufmann.
Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization.
Interphase fluorescence in situ hybridization (FISH) studies of chromosomal region 13q14 were performed to investigate the incidence and clinical importance of deletions in multiple myeloma (MM). Monoallelic deletions of the retinoblastoma-1 (rb-1) gene and the D13S319 locus were observed in 48 of 104 patients (46.2%) and in 28 of 72 (38.9%) patients, respectively, with newly diagnosed MM. FISH studies found that 13q14 was deleted in all 17 patients with karyotypic evidence of monosomy 13 or deletion of 13q but also in 9 of 19 patients with apparently normal karyotypes. Patients with a 13q14 deletion were more likely to have stage III disease (P =.022), higher serum levels of beta(2)-microglobulin (P =.059), and a higher percentage of bone marrow plasma cells (P =.085) than patients with a normal 13q14 status on FISH analysis. In patients with a deletion of 13q14, myeloma cell proliferation (Ki-67) was markedly increased (22.0% +/- 6.9% compared with 15.6% +/- 8.2% in patients without the deletion; P =.0008). Evaluation of bromodeoxyuridine incorporation in 5 patients revealed that both rb-1-deleted and rb-1-normal MM subpopulations were proliferative. The presence of a 13q14 deletion on FISH analysis was associated with a significantly lower rate of response to conventional-dose chemotherapy (40.8% compared with 78. 6%; P =.009) and a shorter overall survival (24.2 months compared with > 60 months; P <.005) than in patients without the deletion. Multivariate analysis of prognostic factors confirmed the independent predictive value of 13q14 deletions for shortened survival. In conclusion, deletions of 13q14 are frequently detected by interphase FISH in patients with newly diagnosed MM, correlate with increased proliferative activity, and represent an independent adverse prognostic feature in MM. (Blood. 2000;95:1925-1930)
Adult↗
Hypertensive cardiovascular damage in patients with primary autonomic failure.
Patients with primary autonomic failure have left-ventricular hypertrophy probably as a result of night-time hypertension.
Autonomic Nervous System Diseases↗
[Healing process and complications after eye muscle surgery].
BACKGROUND: Varying reports on the incidence of operative and postoperative complications following eye muscle surgery have been published. The purpose of this study was to quantify complications after various types of eye muscle surgery as well as minor pathological changes of the anterior and posterior segment. PATIENTS AND METHODS: This prospective study included all patients who underwent eye muscle surgery at the Department of Strabismology and Neuroophthalmology, Giessen, from January to May 1998. Five hundred eyes of 377 patients aged 2-82 years were included. The spectrum of procedures comprised: recessions, resections, tucks, R&R procedures, transpositions, bimedial retroequatorial myopexies, and revisions of rectus and oblique muscles. All patients were examined 1 day preoperatively and 1 day, 1 week, and 3 months postoperatively. Any complications and even minor pathological changes of the anterior and posterior segment were documented. Some changes were assessed by means of a score (0-3). RESULTS: One day postoperatively, 30% of eyes had inflammatory pseudoptosis, most of them mild. Conjunctival swelling and injection were frequently mild and moderate, after 1 week mostly mild. Conjunctival irritation was more pronounced following resection than tucking. Punctate epithelial keratopathy was noted in 1.6% of cases (first postoperative day), dellen in 4.3% (first postoperative week). Three months postoperatively, 14.3% of eyes had biomicroscopically visible conjunctival folds and 91.3% had minimal conjunctival scars. None of the patients had a scleral perforation or other serious complication. CONCLUSIONS: Eye muscle surgery rarely entails complications. Revisions due to organic pathological changes are extremely rare. Possible development of dellen requires check-up 4-7 days postoperatively. Tucking of rectus muscles causes less conjunctival irritation than resection.
Adolescent↗
Lea symbols: visual acuity assessment and detection of amblyopia.
OBJECTIVE: Lea symbols can be used for measuring visual acuity in childhood. Therefore, these symbols might be useful for early detection of amblyopia. We evaluated whether the visual acuity determined with Lea symbols (LS) corresponds to the visual acuity determined with the Landolt-C (LC). PATIENTS AND METHODS: In 55 strabismic amblyopic volunteers aged 5-59 years, the monocular visual acuity of both eyes was determined using LC and LS. For comparison, the right eye of 20 healthy volunteers was examined. Single optotypes (LC, LS) were used in 55 amblyopes and crowded optotypes (LC(17.2), LC(2.6), CLS) in 40 amblyopes. The luminance of the test charts was 180-200 cd/m(2), with a contrast >85%. The refraction of the subjects was corrected beforehand. RESULTS: In the 40 amblyopic eyes tested under each condition, LS exceeded CLS and LC by about 1 line (dB), LC(17.2) by 2 lines and LC(2.6) by 3 lines (mean values +/- SD: LS 0.62+/-1.8 dB, CLS 0.46+/-1.7 dB, LC 0.5+/-2. 0 dB, LC(17.2) 0.41+/-2.3 dB, LC(2.6) 0.29+/-2.3 dB). The non-amblyopic fellow eyes and healthy eyes showed smaller differences (fellow eyes LS 1.32+/-1.1 dB, CLS 1.17+/-1.1 dB, LC 1. 15+/-0.9 dB, LC(17.2) 1.05+/-0.9 dB, LC(2.6) 0.93+/-1.1 dB; healthy eyes LS 1.74+/-0.9 dB, CLS 1.58+/-0.8 dB, LC 1.48+/-0.6 dB, LC(17.2) 1.41+/-0.7 dB, LC(2.6) 1.32+/-1.1 dB). In the amblyopic eyes, the reduction of LC was more distinct than the reduction of LS. Fifty-two amblyopes had an amblyopia >1 dB of LC, LC(17.2) and LC(2. 6), while 50 had an interocular acuity difference >1 dB CLS. CONCLUSIONS: Using Lea symbols, a recognition acuity can be determined and amblyopia can reliably be detected. Due to their design, the Lea symbols are particularly suitable and recommendable for application in young children. However a slight systematic difference between LS and LC has to be considered.
Adolescent↗
Postoperative nausea and vomiting after Faden operation.
OBJECTIVE: The purpose of this study was to evaluate the antiemetic effect of prophylactic dimenhydrinate application prior to Faden operation and to compare the incidence of PONV between bimedial Faden operation (BMF) and horizontal recess-resect procedure (R&R). METHODS: Ninety-nine children (4-10 years) scheduled for BMF were included in this prospective double-blind study. Midazolam (0.5 mg/kg body weight, BW) was administered orally for premedication 30 min before induction of anesthesia. Additionally, children weighing >/=23 kg received either dimenhydrinate suppositories or placebo. The placebo group was compared with 148 children who underwent R&R surgery without antiemetic prophylaxis during the same period. Anesthesia was induced with thiopentone (5-10 mg/kg BW) and vecuronium (0.1 mg/kg BW) bromide and maintained with halothane (1-2 vol%) in N(2)O/O(2) (65/35 vol%). Age, height, weight, and incidence of oculocardiac reflex were documented. PONV was classified into "no vomiting", "vomiting without therapy", and "vomiting requiring rescue medication". In the latter case dimenhydrinate was given again. The chi-square test was used for statistical analysis. RESULTS: Forty-eight patients received placebo, while 51 received dimenhydrinate. No differences between any groups were observed concerning age, height, weight, and incidence of oculocardiac reflex. Compared to R&R surgery, PONV requiring rescue medication occurred significantly more frequently after BMF (45% vs 23% after R&R). PONV after BMF was significantly less severe in the dimenhydrinate group than in the placebo group. The total incidence of PONV after BMF, however, was not significantly reduced. CONCLUSION: The high incidence of PONV after BMF can be explained by the greater invasiveness of BMF than R&R surgery. PONV requiring antiemetic rescue medication can be reduced by preoperative administration of dimenhydrinate suppositories.
Anesthesia, Local↗
Aneuploidy of chromosome 7 can be detected in invasive lung cancer and associated premalignant lesions of the lung by fluorescence in situ hybridisation.
In the present study the chromosomal status of seven invasive non small cell lung cancer specimens and associated premalignant lesions was investigated. By fluorescence in situ hybridisation (FISH) with centromere specific probes, an increase in the percentage of aneuploid cells from pre-invasive to invasive lesions could be demonstrated (mean 8.5 and 59%, respectively, for chromosome 7). Furthermore, mean chromosome copy numbers were higher in invasive carcinomas as compared to premalignant lesions, indicating polyploidization during tumor development. Increasing evidence suggests that aberrations of chromosome 7 occur early in the development of lung cancer. Whether these aberrations can be used as a biomarker for future neoplastic progression remains to be determined.
Aneuploidy↗
Deletions of the p53 gene in multiple myeloma.
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Chromosomes, Human, Pair 17↗
Multiple myeloma with deletion of chromosome 13q is characterized by increased bone marrow neovascularization.
Anti-angiogenesis therapy with thalidomide has been reported to have marked activity in multiple myeloma (MM). As cytogenetics is an independent prognostic factor in MM, we analysed bone marrow (BM) angiogenesis and cytogenetic abnormalities in 34 patients with active MM. BM microvessel density (MVD), as determined by staining with anti-CD34, was significantly higher in MM (MVD: 221 +/- 94 per mm2) than in controls (80 +/- 36; P < 0.0001). In patients with the presence of at least one unfavourable cytogenetic abnormality (deletion of 13q14, deletion of 17p13, aberrations of 11q), a significantly increased BM MVD was observed (254 +/- 93 vs. 160 +/- 60 in patients with absence of these abnormalities; P = 0.0035). Further analyses indicated that increased BM MVD was significantly correlated with deletion of 13q14 (259 +/- 96 vs. 188 +/- 80; P = 0. 026), but not with other cytogenetic, clinical and laboratory MM parameters. We conclude that BM neovascularization is particularly high in MM with deletion of 13q14, which provides a rationale for use of anti-angiogenic strategies in the treatment of MM with high-risk cytogenetics.
Adult↗
Malignant cell detection by fluorescence in situ hybridization (FISH) in effusions from patients with carcinoma.
Cytological diagnosis of malignant cells in effusions is hampered by difficulties in the differentiation from reactive mesothelial cells. Because interphase cytogenetics by fluorescence in situ hybridization (FISH) might complement cytological evaluation, we determined the power of tumor cell detection using FISH and cytology in 201 effusions from patients with advanced cancer. Furthermore, 9 primary breast tumors were FISH-karyotyped, and chromosomal aberrations were compared with those of corresponding metastatic effusion cells. By using centromeric probes representing chromosomes 7, 8, 11, 12, 17, and 18, a rate of malignancy-associated aneusomy combined for the 6 chromosomes was detected in an overall of 44.8% of effusion specimens (range, 31.8% to 39.3% for the individual chromosome), comparable to cytology (43.3%). The combination of just 2 FISH probes (namely, representing chromosome pairs 8/11 and 8/17) was almost equally efficient in the identification of aneusomy. Approximately one fourth of the cytologically negative effusions were FISH positive and vice versa. From the initially FISH-negative effusions, 18.9% could be subsequently classified positive with dual-color FISH by visualization of intranuclear chromosomal complexity in rare aneuploid cells. Thus, "overall FISH analysis," including dual-color evaluation, identified tumor cells in significantly more effusions (55.2%, P = .001) than conventional cytology, implying greater sensitivity. Finally, our finding that numerical aberration patterns in primary breast tumors and corresponding metastatic effusions are comparable indicates that FISH examination of primary tumors will indicate the centromeric probe(s) best suited for an efficient search for metastasis in the individual case.
Adenocarcinoma↗
Predictive role of interphase cytogenetics for survival of patients with multiple myeloma.
PURPOSE: Recent metaphase cytogenetic studies suggested that specific chromosomal abnormalities are of prognostic significance in patients with multiple myeloma (MM). Because the true incidence of chromosomal abnormalities in MM is much higher than that detected by metaphase analysis, we used interphase fluorescence in situ hybridization (FISH) to determine the prognostic value of specific chromosomal aberrations. PATIENTS AND METHODS: Bone marrow plasma cells from 89 previously untreated patients with MM were studied consecutively by FISH to detect the deletions of 13q14, 17p13, and 11q and the presence of t(11;14)(q13;q32). FISH results were analyzed in the context of clinical parameters (response to treatment and survival after conventional-dose chemotherapy), and a multivariate analysis of prognostic factors was performed. RESULTS: By FISH, the deletion of 13q14 occurred in 40 patients (44.9%), deletion of 17p13 in 22 (24.7%), and 11q abnormalities in 14 (15.7%; seven with t(11;14)). Deletions of 13q14 and 17p13 were associated with poor response to induction treatment (46.9% v 77.3% in those without deletions, P =.006 and 40.0% v 73.2%, P =.008, respectively) and short median overall survival (OS) time (24.2 v 88.1 months, P =. 008 and 16.2 v 51.3 months, P =.008, respectively). Short median OS time was also observed for patients with 11q abnormalities (13.1 v 41.6 months, P =.02). According to the number of unfavorable cytogenetic features (deletion of 13q14, deletion of 17p13, and aberrations of 11q) that were present in each patient (0 v 1 v 2 or 3), patients with significantly different OS times could be discriminated from one another (102.4 v 29.6 v 13.9 months, P <.001, respectively). CONCLUSION: For patients with MM who were treated with conventional-dose chemotherapy, interphase FISH for 13q14, 17p13, and 11q provides prognostically relevant information in addition to that provided by standard prognostic factors. This observation may be considered for risk-adapted stratifications of MM patients in future clinical trials.
Antineoplastic Combined Chemotherapy Protocols↗
The biology of multiple myeloma.
Multiple myeloma (MM) is a B-cell malignancy originating from pre-switched, follicle center B-lymphocytes which differentiate to plasma cells accumulating in the bone marrow. MM cells are characterized by a profound genetic instability resulting in a complex set of numerical and structural chromosomal abnormalities. Among these abnormalities, translocations involving 14q32, the immunoglobulin heavy-chain locus, are the most frequent aberrations, but translocation partners are remarkably heterogeneous. Chromosome 13q14 may harbor a critical tumor suppressor gene since MM patients with deletion of 13q14 experience short overall survival after conventional-dose and high-dose chemotherapy. Bone marrow stroma cells support growth and survival of MM cells, which in turn influence the bone marrow microenvironment. This is particularly evident by the markedly increased bone marrow vascularization observed in most patients with active MM.
Chromosomes, Human, Pair 13↗
Three-year follow-up of patients with silent ischemia in the subacute phase of myocardial infarction after thrombolysis and early coronary intervention.
In order to assess the prognostic value of silent myocardial ischemia in acute myocardial infarction after thrombolysis and early coronary angiography (14-48 h after start of thrombolysis) including percutaneous transluminal coronary angioplasty, if indicated, 126 patients underwent 24 h-Holter-monitoring in the early postinfarction period. The 24 h-Holter-recording was initiated directly after early coronary intervention (40+/-11 h after onset of symptoms). Of the 126 patients initially eligible for the study 29 had to be excluded from further analysis for clinical or methodical reasons. Of the remaining 97 patients, 10 (10%) had silent ischemia (group A) and 87/97 (90%) patients showed no significant ST-segment alterations. Both groups did not significantly differ from each other with regard to baseline clinical characteristics, severity of coronary artery disease and frequency of successful percutaneous transluminal coronary angioplasty. The left ventricular ejection fraction showed a trend towards lower values in patients with than in those without silent ischemia (47+/-15% vs. 55+/-13%, p=0.07). When both silent ischemia and left ventricular ejection fraction <40% were present, a subset of patients at high risk for cardiac death could be identified (specificity: 98%, positive predictive accuracy: 75%). By Kaplan-Meier analysis, significantly more cardiac deaths occurred in group A than in group B (30% vs. 6%, p<0.01) during the three-year follow-up (950+/-392 days) after acute myocardial infarction. Regarding the cardiac events during long-term follow-up (emergency percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, non-fatal reinfarction, and cardiac death) there was no significant difference between both groups (30% vs. 18%, NS). In conclusion, Holter monitor-detected silent ischemia in the subacute phase of myocardial infarction after thrombolysis followed by early delayed coronary intervention occurs in 10% of the patients indicating either a residual ischemia in the infarcted zone despite a combined reperfusion strategy or a remote ischemic potential in case of multivessel disease. In this small selected group of infarct patients too, silent ischemia is to be considered as an important non-invasive parameter to predict cardiac death during long-term follow-up and provides valuable complementary information to left ventricular dysfunction, a well established prognostic marker in the postinfarction period.
Adult↗
Influence of low temperature on productivity, proteome and protein phosphorylation of CHO cells.
Proliferation of mammalian cells can be controlled by low cultivation temperature. However, depending on cell type and expression system, varying effects of a temperature shift on heterologous protein production have been reported. Here, we characterize growth behavior and productivity of the Chinese hamster ovary (CHO) cell line XM111-10 engineered to synthesize the model-product-secreted alkaline phosphatase (SEAP). Shift of cultivation temperature from 37 degrees C to 30 degrees C caused a growth arrest mainly in the G1 phase of the cell cycle concomitant with an up to 1.7-fold increase of specific productivity. A low temperature cultivation provided 3.4 times higher overall product yield compared to a standard cultivation at 37 degrees C. The cellular and molecular mechanisms underlying the effects of low temperature on growth and productivity of mammalian cells are poorly understood. Separation of total protein extracts by two-dimensional gel electrophoresis showed altered expression levels of CHO-K1 proteins after decrease in cultivation temperature to 30 degrees C. These changes in the proteome suggest that mammalian cells respond actively to low temperature by synthesizing specific cold-inducible proteins. In addition, we provide the first evidence that the cold response of mammalian cells includes changes in postranslational protein modifications. Two CHO proteins were found to be phosphorylated at tyrosine residues following downshift of cultivation temperature to 30 degrees C. Elucidating cellular events during cold exposure is necessary for further optimization of host-cell lines and expression systems and can provide new strategies for metabolic engineering.
Alkaline Phosphatase↗
Hyperdiploidy and apparent aneusomy in mesothelial cells from non-malignant effusions as detected by fluorescence in situ hybridization (FISH).
Interphase cytogenetics by fluorescence in situ hybridization (FISH) can be used to detect malignant cells characterized by chromosomal aneuploidy. However, apparent aneusomy in normal "control" tissues has to be considered when using FISH as diagnostic tool. In effusions as model tissue exposed to metastasis, the definition of cut-off levels for background aneusomy by FISH was aimed in this study. Using centromeric probes representing chromosomes 7, 8, 11, 12, 17 and 18, extensive chromosome copy number enumeration by single-color FISH analysis was performed in pleural and ascitic effusions derived from 15 patients with various, non-malignant diseases. In all effusions, cells with gain of hybridization signals for several or all chromosomes tested were found (in up to 1.94% of cells). A consistent finding was high grade hyperdiploidy (>4 centromeric signals). Mesothelial elements mainly contributed to hyperdiploidy in effusions, as demonstrated by a combined analysis of FISH and immunocytochemistry with staining for cytokeratin. Dual-color FISH analysis showed that hyperdiploidy was predominantly corresponding to polyploidization; however, there were always minor cell populations classified as aneuploid by dual-color FISH. In conclusion, stringent criteria have to be applied to distinguish malignancy-related aneuploidy from background aneusomy by FISH.
Adult↗
Consensus statement on the diagnosis of multiple system atrophy.
We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible MSA requires one criterion plus two features from separate other domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poorly levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation.
Autonomic Nervous System Diseases↗
[Causes of blindness in Hessia in 1996].
BACKGROUND: Despite of medical progress, the incidence and prevalence of blindness are continuously increasing. In Hessia, the number of persons receiving blindness compensation payment increased from 8,346 in 1985 to 11,166 in 1996 by 2.6% per year. In 1996, the rate (prevalence) amounted to 1.85/1000 of the Hessian population. METHODS: In this study, the incidence of blindness (visual acuity < or = 0.02 or equivalent visual handicap) and substantial visual handicap (visual acuity < or = 0.05 or equivalent visual handicap) according to the Hessian law was investigated by means of the records of new candidates for blindness compensation payment whose applications were granted in 1996. The causes of blindness (main diagnosis), visual acuity, age, gender, and nationality were evaluated. RESULTS: The Hessian administration for public welfare had filed 2,609 alterations of applications concerning sundry social assistance. Out of these, 2,395 files (91.8%) were available, 1411 applications met the requirements for blindness compensation payment, 45.4% were graded substantially visually handicapped for the first time, 43.4% were graded blind for the first time, and 11.0% were graded blind after previous substantial visual handicap. In 0.2%, a further classification was not necessary. Applied to the Hessian population of 6.027 million people, the incidence of blindness was 0.14/1000. 67.9% were female, 30.9% were male, in 1.2% the gender was not evaluable. The age median of the candidates was 78 years (male: 74 years, female: 80 years), 84.3% of the candidates were > or = 60 years old. The most frequent causes of blindness (substantial visual handicap) were: age related macular degeneration 35.3% (49.5%), diabetic retinopathy 15.0% (17.0%), glaucoma 12.6% (7.8%), tapetoretinal degenerations 6.9% (1.7%), optic nerve atrophy 6.1% (4.3%), and myopia 5.0% (6.5%). CONCLUSION: Age related affections are the most frequent causes of blindness. Due to the increasing life expectancy and rather constant birth rates, a further increase of blindness rates has to be expected.
Adolescent↗
[Disturbances of binocular vision in macular heterotopia].
BACKGROUND: Tractive translocation of the macula (secondary macular heterotopia) may result in disturbance of binocular vision. The report of a case shall discuss the sensorial problems of these patients. HISTORY AND SIGNS: We report of a 40-years old male who had decreased visual acuity and loss of binocular vision for several years due to episodes of uveitis with intravitreous hemorrhage and cataract formation. After bilateral vitrectomy and cataract extraction a good visual acuity was restored in both eyes. Postoperatively, the patient monocularly complained about disturbed egocentric localization (tilting of the visual environment, "past-pointing") and metamorphopsia. Binocularly he was confused by doubled vision with tilted images. Both maculae showed a tractive translocation of 15 degrees downward. Measurements of binocular alignment with the tangent screen showed an excyclotropia of 8 degrees and an exotropia of 7 degrees in all directions of gaze. Haploscopic examination with fusion images demonstrated that sensorial fusion was not possible even with perfect ocular alignment due to disturbed relative retinal localization (obligate fixation disparity). THERAPY AND OUTCOME: Initially, full time occlusion of the left eye was required. After improvement of symptoms occlusion therapy was slowly tapered. Within one year the patient had learned to suppress the image of his left eye and reported only minor residual visual disturbances even without occlusion of his left eye. CONCLUSIONS: Secondary translocation of the macula monocularly results in a disturbance of egocentric localization and in metamorphopsia. Binocularly doubled vision with tilted images and a loss of sensorial fusion are seen. With monocular vision, perceptual adapting to the aberration in egocentric localisation is possible within weeks by reallocation of the retinal meridians in the central nervous system. Binocular improvement of symptoms is limited to the learning of suppression. Improvement of binocular symptoms by adaptation of retinal correspondence does not occur.
Adult↗