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Biomedical subjects

G Becker

Publications and source records attributed to G Becker.

At least 19 recordsLinked to original sources
PubMed2003

[Multimodal treatment strategy for Langerhans cell histiocytosis at head and neck manifestations].

Langerhans cell histiocytosis (LCH) is a rare disorder with different clinical features. An established standardized treatment does not exist.We present a case report of a patient with localized LCH of the temporal bone and discuss the interdisciplinary treatment strategies. We reviewed the international literature and summarized the current knowledge. Beside a wait and see policy in cases without symptomatic disease, surgery, radiotherapy or chemotherapy, and combinations of these options are used as treatment modalities. While surgery or radiotherapy are preferred in localized (symptomatic) lesions, stage-adapted chemotherapeutic regimens are the treatments of choice in disseminated disease. Treatment selection depends on the individual clinical features.

Adolescent↗
PubMed2003

[Methods for the early diagnosis of Parkinson's disease].

Patients with idiopathic Parkinson's disease display a 60% degeneration of the nigrostriatal neurons before motor symptoms have progressed enough to allow clinical diagnosis. It is clear that any neuroprotective therapy starting at such a late stage can have no substantial effect on the disease progression. Therefore, earlier diagnosis must be the goal of future research,when at most mild motor or non-motor symptoms are present or when only risk factors can be identified. Evidence of various gene mutations associated with idiopathic Parkinsonism raise the hope that these or other biological markers will allow earlier identification of patients at risk. A possibly significant vulnerability factor for developing Parkinson's disease can also be demonstrated by means of transcranial sonography. Since the individual tests are not sufficiently specific or sensitive, a gradual, precise, and inexpensive battery of tests needs to be developed for the successful identification of a risk group for this disease. The extent of damage to the dopaminergic system in these patients can be quantified using nuclear techniques.

Autoantibodies↗
PubMed2003

Superficial siderosis of the central nervous system: pathogenetic heterogeneity and therapeutic approaches.

OBJECTIVE: Superficial siderosis of the central nervous system (CNS) is a rare chronic progressive disorder caused by chronic subarachnoid hemorrhage. We present four patients with superficial siderosis of the CNS to describe the characteristic symptoms, and to discuss the pathogenetic heterogeneity and possible new therapeutic approaches. RESULTS: The causes of chronic subarachnoid bleeding in superficial siderosis were different. In two patients surgical treatment of ependymoma or cerebral cavernomas were the underlying diseases. No cause was detected in one patient. For the first time, we present one patient with vasculitis of the central nervous system associated with systemic hemochromatosis in superficial siderosis. Therapeutic approaches included exstirpation of cavernomas as the source of chronic bleeding in one patient, immunosuppressive therapy and venupunctures in the patient with vasculitis and hemochromatosis, and symptomatic treatment with chelating agents and antioxidants. The patients remained clinically stable for the follow-up period of up to 2 years. CONCLUSIONS: Our cases underline the pathogenetic heterogeneity of superficial siderosis and favor the early diagnosis for prompt initiation of therapy. Besides treatment of the underlying condition, antioxidants and radical scavengers may be effective in halting the progression of the disease.

Adult↗
PubMed2002

Bioaerosol exposure during refuse collection: results of field studies in the real-life situation.

To determine the bioaerosol exposure of refuse collectors, field measurements were performed under real working conditions within the framework of a research project. Influencing variables such as different types of refuse, community structure, collection interval and season were taken into account. Overall, 1612 samples were taken in towns of Westfalia, Germany. With workplace levels on a scale of 10(3) to less than 10(4) CFU/m3 for the loader, the results show a surprisingly low total fungi concentration in comparison with earlier studies. Total bacteria concentrations, in contrast, were largely on a scale of 10(4) CFU/m3, with 10(5) CFU/m3 being registered sporadically, especially in apartment-block districts. Endotoxin levels were high especially in the summer months, occasionally reaching values of more than 50 EU/m3, whereas they were normally below 10 EU/m3 in autumn and winter. Inside the cab, the exposure level for the entire spectrum was at least one power of ten lower. The factors believed to account primarily for the low total fungi concentration were workplace hygiene, the prevailing 1-week collection interval, and the low in-process exposure time resulting from the effective deployment of automatic lifting devices. In contrast, the type of refuse was not found to have a significant influence.

Aerosols↗
PubMed2002

Sonographic imaging of the brain parenchyma.

Using B-mode transcranial sonography (TCS), it is possible to image the brain parenchyma through the intact skull with conventional low-frequency probes. Several brain disorders can be depicted by TCS such as bleedings, brain tumors, or enlargement of the ventricular system. More recently there is evidence that TCS findings can complement information from other neuroimaging techniques in neurodegenerative disorders leading to new insights and pathophysiological concepts.

Brain Neoplasms↗
PubMed2002

Cytosine deaminase and thymidine kinase gene therapy in a Dunning rat prostate tumour model: absence of bystander effects and characterisation of 5-fluorocytosine metabolism with 19F-NMR spectroscopy.

The rat prostate tumour cell line R3327 AT-1 was transfected with a gene coding for a fusion protein comprised of cytosine deaminase (CD from E. coli) and thymidine kinase (TK from Herpes simplex virus, HSV-1). The resulting AT-1/CDglyTK cell line was sensitive to the prodrug 5-fluorocytosine (IC(50) = 78 microM, 96-h incubation) via CD and to ganciclovir (GCV, IC(50) = 1 microM, 96 h) via TK. Subcutaneous tumours generated from 100% CDglyTK(+) cells responded well to 5-FC therapy (500 mg/kg, i.p., 14 daily treatments, four out of seven animals in remission) and to GCV therapy (30 mg/kg, i.p., 14 daily treatments, five of six animals in remission). However, experiments with mixtures of CDglyTK(+) and CDglyTK(-) cells showed low levels of connexins (intercellular gap junctions) and no bystander effect for nontransfected cells using either 5-FC or GCV therapy. Furthermore, (19)F-NMR spectroscopy showed that incubation of cultured CDglyTK(+) cells with 774 microM 5-FC for 16 h resulted in the following intracellular concentrations: 5-FC = 314 microM, 5-FU = 52 microM, cytotoxic fluoronucleotides = 163 microM; extracellular 5-FU reached only 6.4 microM. Thus, in this model system intracellular trapping of 5-FU (slow export) contributes to the failure of the CD/5-FC bystander effect via an extracellular route.

Animals↗
PubMed2002

Clinical features of Fabry's disease in Australian patients.

BACKGROUND: Anticipating the prospect of specific treatment, we studied a large group of Australians with Fabry's disease. AIMS: We aimed to: (i) document the clinical features of Fabry's disease in Australian patients, (ii) test the hypothesis that clinical features vary with specific mutation and blood group and (iii) assess small-fibre peripheral nerve function. METHODS: A questionnaire was forwarded to all Australian patients known to us. Patients were invited to attend for clinical, renal cardiac, ophthalmological and neurological assessment. RESULTS: Sixty-seven patients (29 men and 38 women) from 18 families participated. Diagnosis in index cases was delayed by > or = 10 years in nearly all families. Common clinical features are: (i) episodic acroparaesthesia (100% of hemizygotes; 53% of heterozygotes), (ii) anhydrosis (93%; 1%), (iii) characteristic rash (93%; 13%), (iv) renal disease (69%; 21%), (v) ischaemic heart disease (28%; 26%), (vi) palpitations (62%; 29%), (vii) mitral valve murmurs (37%; 23%) and (viii) premature cerebrovascular disease (31%; 5%). Ophthalmic findings of cornea verticillata (96%; 76%) and anterior cataract (48%; 14%) were common. Findings were variable within and between families. In women, anhydrosis reliably predicts the presence of significant Fabry's renal disease. Small nerve fibre testing using quantitative sensory testing was clearly abnormal in 95% of male patients, and in those female patients with paraesthesiae. CONCLUSIONS: Symptoms of anhydrosis, acroparaesthesiae, rash and renal disease suggest diagnosis of Fabry's. Women are commonly symptomatic, and the advent of therapy highlights the practical advantage of earlier diagnosis.

Adult↗
PubMed2002

Stereotactic fractionated irradiation of optic nerve sheath meningioma: a new treatment alternative.

BACKGROUND: Primary optic nerve sheath meningioma (ONSM) is a rare but almost invariably blinding tumour when its natural history is observed in a "wait and see" strategy. Surgery has hitherto only been advocated in case of progressive disease involving intracranial structures, as it leads to iatrogenic blindness in the overwhelming majority of cases. Therefore, treatment options bearing lesser risk of functional deterioration are highly desirable, both in cases of intracranial involvement as well as during earlier phases of the disease which are currently generally left untreated. The authors report the outcome of the largest series of patients to date treated by stereotactic fractionated irradiation as a new treatment approach in ONSM at all stages. METHODS: 15 patients (16 nerves) underwent stereotactic fractionated conformal irradiation with a total dose of 54 Gy, using standard fractionation. Main outcome parameters included visual acuity and visual field, as well as three dimensional remission as documented by imaging. RESULTS: Tumour control was confirmed in all 15 patients undergoing stereotactic fractionated conformal irradiation (mean follow up 37 (range 12-71) months). No patient developed functional deterioration during or after treatment. Moreover, visual acuity improved by more than two lines in one patient and the visual field improved in six cases. Visual outcome in the other patients remained unchanged. There were no significant side effects of radiation therapy. CONCLUSION: These data provide convincing evidence that stereotactic fractionated conformal irradiation is an effective treatment option for primary ONSM with minimal treatment related morbidity. It should therefore be considered as therapeutic option both in early stage ONSM where surgery cannot be justified as well as in later stages, where surgery is so far considered the first line approach.

Adolescent↗
PubMed2001

Evidence for disturbances of copper metabolism in dystonia: from the image towards a new concept.

The pathogenesis of idiopathic adult onset dystonia (ID) is still unclear. Although neuropathologic studies did not reveal consistent abnormalities, electrophysiologic and neuroimaging findings point toward a disinhibition and overactivity of the frontal motor cortical areas caused by an altered basal ganglia outflow. The lentiform nuclei are assumed to play a major role in this scenario. Recent neurochemical analysis of brain tissue stimulated by transcranial ultrasound studies demonstrated an increased copper content of the lentiform nuclei in patients with ID. The shift of brain copper level may substantially influence neuronal activity causing a reduced inhibitory output from the lentiform nuclei to the motor cortex. The reason for the presumably altered copper metabolism is not clear, but preliminary findings suggest that reduced levels of the Menkes protein, a membrane ATPase exporting copper out of the cells, may be implicated. Disturbances of brain copper metabolism may explain various phenomena of ID; however, it needs to be determined whether these observations represent the basic pathogenetic mechanism of ID or reflect another as yet unidentified pathologic process.

Basal Ganglia↗
PubMed2001

Echogenicity of substantia nigra determined by transcranial ultrasound correlates with severity of parkinsonian symptoms induced by neuroleptic therapy.

BACKGROUND: Increased echogenicity of the substantia nigra (SN) detected by transcranial sonography is a characteristic ultrasound feature of Parkinson's disease. This ultrasound feature can also be detected in a subgroup of healthy adults. In recent studies, healthy subjects with this ultrasound feature showed a reduced [(18)F]-Dopa uptake on positron emission tomography (PET), indicating a subclinical alteration of the nigrostriatal system. This study was designed to evaluate whether the severity of neuroleptic side effects is related to the echo-feature of the SN. METHODS: In the retrospective part of the study, 93 psychiatric patients with either definite and severe parkinsonism after neuroleptic treatment (n = 52) or with no or minimal parkinsonian symptoms (n = 41) were included and underwent transcranial sonography to measure the extension of hyperechogenic areas at the SN. In addition, in the prospective part 11 patients with an acute psychotic episode requiring first-ever neuroleptic treatment underwent ultrasound examination. Subsequently, neuroleptic-induced parkinsonian signs were assessed prospectively. RESULTS: In the retrospective part of the study, patients with severe neuroleptic-induced parkinsonism had more extended echogenic signals at the SN than those with low echogenic SN (U-test; p <.01). The prospective part of the study showed that the severity of parkinsonian symptoms correlated with the echogenicity of the substantia nigra (Spearman's rank: p <.01). CONCLUSIONS: Increased echogenicity of the substantia nigra is associated with impaired function of the nigrostriatal system that can be disclosed by neuroleptic drugs.

Acute Disease↗
PubMed2001

Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data.

PURPOSE: To examine the efficacy of ACE inhibitors for treatment of nondiabetic renal disease. DATA SOURCES: 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens including ACE inhibitors to the efficacy of regimens without ACE inhibitors in predominantly nondiabetic renal disease. STUDY SELECTION: Studies were identified by searching the MEDLINE database for English-language studies evaluating the effects of ACE inhibitors on renal disease in humans between May 1977 (when ACE inhibitors were approved for trials in humans) and September 1997. DATA EXTRACTION: Data on 1860 nondiabetic patients were analyzed. DATA SYNTHESIS: Mean duration of follow-up was 2.2 years. Patients in the ACE inhibitor group had a greater mean decrease in systolic and diastolic blood pressure (4.5 mm Hg [95% CI, 3.0 to 6.1 mm Hg]) and 2.3 mm Hg [CI, 1.4 to 3.2 mm Hg], respectively) and urinary protein excretion (0.46 g/d [CI, 0.33 to 0.59 g/d]). After adjustment for patient and study characteristics at baseline and changes in systolic blood pressure and urinary protein excretion during follow-up, relative risks in the ACE inhibitor group were 0.69 (CI, 0.51 to 0.94) for end-stage renal disease and 0.70 (CI, 0.55 to 0.88) for the combined outcome of doubling of the baseline serum creatinine concentration or end-stage renal disease. Patients with greater urinary protein excretion at baseline benefited more from ACE inhibitor therapy (P = 0.03 and P = 0.001, respectively), but the data were inconclusive as to whether the benefit extended to patients with baseline urinary protein excretion less than 0.5 g/d. CONCLUSION: Antihypertensive regimens that include ACE inhibitors are more effective than regimens without ACE inhibitors in slowing the progression of nondiabetic renal disease. The beneficial effect of ACE inhibitors is mediated by factors in addition to decreasing blood pressure and urinary protein excretion and is greater in patients with proteinuria. Angiotensin-converting inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and proteinuria and, possibly, those without proteinuria.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Relationship of substantia nigra echogenicity and motor function in elderly subjects.

BACKGROUND: Patients with Parkinson's disease (PD) exhibit an increased echogenicity of the substantia nigra (SN) on transcranial sonography. Some healthy adults with the same echo characteristics showed a reduced 18fluorodopa uptake on PET, indicating a subclinical alteration of the nigrostriatal system. OBJECTIVES: To determine whether the sonographic phenotype of hyperechogenic SN has any relevance for motor function in elderly subjects and whether an increased echogenicity of the SN is associated with an impaired motor function. METHOD: In a population-based, cross-sectional study, 93 subjects older then 60 years without history of extrapyramidal disorder underwent sonographic and neurologic examinations, with a quantitative motor assessment. RESULTS: Elderly healthy subjects without prediagnosed extrapyramidal disorder but with SN hyperechogenicity had more frequent and more severe parkinsonian symptoms and a slower finger tapping than those with a regular echogenicity of the SN (p < 0.05, U test). CONCLUSION: With increasing age, subjects with SN hyperechogenicity develop a more substantial slowing of movements than subjects without this echo pattern, stressing the functional relevance of this sonographic finding. The authors speculate that hyperechogenicity of the SN may be detected by transcranial sonography early in life and may serve as a risk marker for nigral injury, although only a minority of these subjects will develop the full clinical picture of PD.

Aged↗
PubMed2001

Neuroimaging in basal ganglia disorders: perspectives for transcranial ultrasound.

Transcranial sonography is a new diagnostic tool, allowing not only the evaluation of cerebral arteries but also the two-dimensional display of the brain parenchyma. In this review we will summarize basics of the application, the ultrasound anatomy of the brain and sonographic findings in some movement disorders. While in normal adults basal ganglia nuclei are hypoechogenic, they are hyperechogenic in certain basal ganglia disorders. In Parkinson's disease, for example, the substantia nigra can be depicted as a distinctly echogenic area. An elevated echogenicity of the lentiform nuclei was noticed in patients with primary adult-onset dystonia. In both disorders the altered echogenicity may arise from higher heavy metal tissue content (i.e. iron in Parkinson's disease and copper in primary dystonia). Our findings converge to the hypothesis that transcranial ultrasound sensitively detects pathological metal accumulation not identified by other neuroimaging techniques (CT and MRI) and therefore provides new insights in the diagnosis of basal ganglia disorders. The implications of these findings for the understanding of the pathogenesis and its usefulness for the early diagnosis of movement disorders are outlined.

Basal Ganglia Diseases↗
PubMed2001

Clinical indications and biological mechanisms of splenic irradiation in autoimmune diseases.

BACKGROUND: Splenic irradiation (SI) is a fairly unknown treatment modality in autoimmune disorders like autoimmune thrombocytopenia (AIT) or autoimmune hemolytic anemia (AIHA), which may provide an effective, low toxic and cost-effective treatment for selected patients. PATIENTS, MATERIALS AND METHODS: This article reviews the limited experiences on splenic irradiation in autoimmune thrombocytopenia by analyzing the current studies including 71 patients and some preliminary reports on splenic irradiation in autoimmune hemolytic anemia. RESULTS: In autoimmune thrombocytopenia between 40 and 90% of all patients responded, but most of them relapsed within 4 to 6 months after splenic irradiation. Between 10 and 20% of all patients had a sustained response. The efficacy of splenic irradiation in HIV-associated cases of thrombocytopenia is probably lower than in other forms of autoimmune thrombocytopenia, but especially in this group immunosuppressive drug treatment of autoimmune thrombocytopenia exposes some problems. In autoimmune hemolytic anemia there are some case reports about efficacy of splenic irradiation. Toxicity of splenic irradiation in both diseases was very moderate. CONCLUSIONS: For HIV patients, for elderly patients or patients at high risk for complications following splenectomy splenic irradiation might be a treatment option. Splenic irradiation as preoperative treatment in patients not responding to or not suitable for immunosuppressive drugs prior to splenectomy may be a promising new application of splenic irradiation to reduce adverse effects of splenectomy in thrombocytopenic patients. A further analysis of the biological mechanisms underlying splenic irradiation may help to improve patient selection, to optimize dose concepts and treatment schedules and will improve understanding of radiotherapy as an immunomodulatory treatment modality.

Age Factors↗
PubMed2001

[Heidelberg Centenarian Study: theoretical and methodological principles for social science research of the oldest old].

This paper addresses two important issues of oldest old research. First, we try to answer the question whether differences between extremely old persons are based on enduring aging processes of physical, social and psychological functions, or whether they are the result of selective survival weeding out the frail. Both trajectories predict low variability, but on different levels. Second, we investigate to which extent the variability of extremely old persons can be assessed by traditional psychosocial instruments. One hundred and fifty six centenarians were contacted, of whom 91 centenarians and 86 proxies participated in this study. The distribution of the cognitive status reveals a high amount of variability. In contrast, with respect to functional capacity 83% receive support from the German Statutory Insurance System for Long-Term Care. The higher variability in the psychological variable points to adaptive potential. We assume that in extreme old age various resources are used to maintain physical functioning above a critical threshold.

Activities of Daily Living↗
PubMed2001

Echogenicity of the substantia nigra in Parkinson's disease and its relation to clinical findings.

Recently an increased echogenicity of the substantia nigra (SN) in patients with Parkinson's disease (PD) was demonstrated by transcranial ultrasound (TCS). In this study we set out to compare SN echogenicitiy with disease characteristics (time of onset, duration, toxin exposure) in a large patients sample. Patients' history and exposure to toxins were recorded from 112 PD patients who underwent a thorough neurological examination including assessment of disease stage according to Hoehn and Yahr and CURS (Columbia University Rating Scale). Personality was assessed according to the Freiburg Personality Inventory. In all patients the area of SN echogenicity was encircled and measured by TCS. All except 9 patients had hyperechogenic SN areas exceeding the mean plus standard deviation values of an age matched control group (0.19 cm2). The age of disease onset was lower in patients who displayed an area of SN echogenicity above this value. The area of SN echogenicity was larger contralateral to the side with more severe symptoms. None of the other characteristics correlated with ultrasound findings. We conclude that SN hyperechogenicity is a typical finding in PD. The cause of hyperechogenicity is so far unknown. Investigation of the underlying reason might disclose a pathogenic factor in PD.

Aged↗
PubMed2001

Morphine in tardive and idiopathic dystonia (short communication).

Opioids have been shown to improve L-Dopa induced dyskinesias in patients with Parkinson's disease. In this pilot trial of five patients with tardive and four patients with idiopathic dystonia we tested the effect of morphinsulfate in a retarded form with a dosage of 20-60 mg per day. A substantial improvement of dystonic movements could be observed in four patients with tardive and one patient with idiopathic dystonia. The effect was only transient in tardive dystonia while pain relief mediated by morphine overlasted the effect on involuntary movements.

Adult↗