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Biomedical subjects

R Gerlach

Publications and source records attributed to R Gerlach.

At least 19 recordsLinked to original sources

Active secretion of S100B from astrocytes during metabolic stress.

In patients suffering from cerebrovascular diseases and traumatic brain damage, increases in serum levels of protein S100B are positively correlated with the severity of the insult. Since high concentrations of S100B have been shown to exert neurotoxic effects, the objective of this study was to characterize the regulatory mechanisms underlying control of S100B release from astrocytes. To that end, we analyzed the kinetics and amount of S100B release in correlation with regulation of S100B gene expression in an in vitro ischemia model. Astrocyte cultures were treated with combined oxygen, serum and glucose deprivation, serum and glucose deprivation or hypoxia alone for 6, 12 and 24 h, respectively. While oxygen, serum and glucose deprivation triggered the most rapid release of S100B, serum and glucose deprivation provoked comparable levels of released S100B at the later time points. In contrast to oxygen, serum and glucose deprivation and serum and glucose deprivation, hypoxia alone elicited only marginal increases in secreted S100B. Parallel analysis of extracellular lactate dehydrogenase and the number of viable cells revealed only moderate cell death in the cultures, indicating that S100B was actively secreted during in vitro ischemia. Interestingly, S100B mRNA expression was potently downregulated after 12 and 24 h of oxygen, serum and glucose deprivation, and prolonged oxygen, serum and glucose deprivation for 48 h was associated with a significant reduction of S100B release at later time intervals, whereas lactate dehydrogenase levels remained constant. Our data suggest that secretion of S100B during the glial response to metabolic injury is an early and active process.

Animals↗

Isolated vasculitis of the stomach: a novel or rare disease with a difficult differential diagnosis.

In up to 80 % of patients with vasculitis, signs of the disease are also seen in the gastrointestinal tract. However, no cases of exclusively gastric vasculitis have previously been reported. We report here the case of a 45-year-old woman with upper abdominal discomfort (no arthropathy), with gastroscopic and endoscopic ultrasound (EUS) findings that mimicked scirrhous gastric carcinoma. Gastroscopy revealed giant gastric folds and a suspicious antral ulcer (with histological findings suggesting chronic active pangastritis). EUS showed a concentric, thickened gastric wall (8 mm) with "pseudolamellation" and more than five enlarged lymph nodes in the paragastric region (lesser curvature). On the basis of suspected scirrhous gastric carcinoma, the patient underwent a four-fifths gastric resection of the altered parts of the gastric tissue. The postoperative course was uneventful. Histological examination of the specimen revealed severe obliterative panvasculitis of the stomach. During a 22-month follow-up period, no signs or symptoms of systemic primary or secondary vasculitis were found in the patient's medical history, symptoms, laboratory parameters, or imaging. This case shows for the first time that a specific gastric panvasculitis can occur, either as a preliminary stage of the condition or as a distinct manifestation of vasculitis associated with the stomach alone. Gastric resection appears to be indicated in patients with isolated obliterative gastric vasculitis, since it avoids the side effects of long-term immunosuppressive therapy and provides prognostic information that takes account of the differential diagnosis of scirrhous gastric carcinoma.

Diagnosis, Differential↗

The Australian EEG database.

The Australian EEG Database is a web-based de-identified searchable database of 18,500 EEG records recorded at a regional public hospital over an 11-year period. Patients range in age from a premature infant born at 24 weeks gestation, through to people aged over 90 years. This paper will describe the history of the database, the range of patients represented in the database, and the nature of the text-based and digital data contained in the database. Preliminary results of the first two studies undertaken using the database are presented. Plans for sharing data from the Australian EEG database with researchers are discussed. We anticipate that such data will be useful in not only helping to answer clinical questions but also in the field of mathematical modeling of the EEG.

Adolescent↗

[Radiotherapy for Graves' ophthalmopathy].

Graves' ophthalmopathy (GO) is the most frequent extrathyroidal manifestation of Graves' disease, an autoimmune disorder of the thyroid, whereas the precise pathogenesis still remains unclear. In Hashimoto's thyroiditis the occurrence of proptosis is an extremely rare event. The therapy for middle and severe courses of GO shows in partly disappointing results, although several therapy modalities are possible (glucocorticoid therapy, radiotherapy, antithyroid drug treatment, surgery). All these therapies lead in only 40 - 70 % to an improvement of the pathogenic symptoms. An intensive interdisciplinary cooperation is necessary to satisfy the requirements for the treatment of Graves' ophthalmopathy. As a consequence of the very different results of the few of clinical studies that were accomplished with reference to this topic, treatment by radiotherapy in the management of the disease is presently controversially discussed. In the German-speaking countries the radiotherapy is, however, firmly established as a therapy option in the treatment of the moderate disease classes (class 2-5 according to NO SPECS), especially if diplopia is present. This article describes the sequences, dosages and fractionation schemes as well as the risks and side effects of the radiotherapy. Altogether, radiotherapy is assessed as an effective and sure method. The administration of glucocorticoids can take place before the beginning of or during the radiotherapy. For the success of treatment the correct selection of patients who may possibly profit from a radiotherapy is absolutely essential. By realising that GO proceeds normally over a period of 2-5 years, which is followed by a period of fibrotic alteration, the application of the radiotherapy in the early, active phase is indispensable. A precise explanation for the effects of radiotherapy in treatment of the GO does not exist at present. The determination of the most effective irradiation doses was made from retrospectively evaluated collectives. Recently the results of a national survey of all German RT departments were published, initiated by the working group of the DEGRO (German Society of Radiooncology). In the most of the German radiooncology departments irradiation with 8 to 10 x 1.8-2.0 Gy 5 x weekly to 16 or 20 Gy is standard. Two recently published prospective German studies pointed out the equivalence of the effectiveness of a short therapy in low dose ranges up to 2.4 Gy as well as of a low proportioned irradiation during a longer period in relation to a standard therapy with 20 Gy. That is why at the moment it is not possible to give a definite recommendation with reference to dosages or the fractionation schemes. In 2003 the first European group (European Group on Graves ' Orbitopathy Experience -- EUGOGO) was founded for pursuing investigations of GO in multi-centric studies, mainly to improve therapy results.

Diplopia↗

[Radiotherapy of eye and orbit tumors].

Malignant diseases of the orbit are multifaceted and require in the majority of the cases an interdisciplinary treatment. Advances in radiotherapy, surgery and chemotherapy make a high cure rate possible, especially in children's tumors. In adults these tumors reach a tumor control rate of nearly 90 %, even with preservation of the eye in most of the cases. There are only two curative therapy options for tumors in this region: radiotherapy and surgery. The therapy for tumors of the eye and the orbit require the total spectrum of the radiotherapeutic techniques depending on the tumor entity, its spread and localization. In a prevailing number of malignant tumors (tumors of the eyelids, tear glands, orbit, metastases) the application of the radiotherapy as an external, fractionated radiotherapy is standard practice, if necessary in combination with operation and/or chemotherapy. Particularly in the therapy for ocular tumors brachytherapy with radionuclides (e. g., ruthenium) is possible and in a few centers world-wide proton therapy is available. As an alternative procedure in special modalities, stereotactic radiotherapy may be considered. Altogether the new radiotherapy techniques permit a dose increase in the tumor region and/or a reduction of the doses to healthy tissues and lead so to a better local tumor control rate and a decrease in acute and chronic side effects.

Brachytherapy↗

Raman spectroscopy of tissue samples irradiated by protons.

PURPOSE: Since the number of cancer patients treated by proton irradiation has increased in the last few years, it seems appropriate to study dose-dependent effects of proton irradiation on mammalian tissues in more detail. MATERIALS AND METHODS: Tissue samples of normal skin of mouse and swine, of a human tumour model xenograph, and of normal skin and a skin tumour (basal cell carcinoma) of a human patient of about 1 mm thickness were irradiated by 24 MeV protons (uniform delivered doses of 1, 7 and 50 Gy: skin of mouse and a human tumour model xenograph, and 0.5, 5 and 50 Gy: swine and human skin). Raman spectra of non-irradiated and irradiated samples were recorded and analysed. RESULTS: Amide I, P=O and C-O bond vibrations and aromatics were sensitive to the proton irradiation dose. In the C-H stretching region, the irradiation-mediated change of Raman spectra was significant only in the case of the skin tumour. CONCLUSIONS: It has been shown that Raman spectroscopy is suited to assess the radiation damage done to biological samples by protons. Proteins of the human skin tumour seem to be more sensitive to proton irradiation than proteins of normal human skin.

Animals↗

A description of an HPLC assay of coproporphyrinogen III oxidase activity in mononuclear cells.

Coproporphyrinogen III oxidase is deficient in hereditary coproporphyria. An activity assay for this enzyme in mononuclear cells, besides the preparation of the substrate, are presented. The separation conditions for the product of the test protoporphyrin IX by gradient, reversed-phase high-performance liquid chromatography are given. The normal value from mononuclear cells of healthy volunteers was 138 +/- 21 pkat/g total soluble protein (mean +/- SD). The enzyme activity of a family with hereditary coproporphyria was measured. The gene carriers exhibit a specific coproporphyrinogen III oxidase activity of 61-90 pkat/g total soluble protein.

Adult↗

Supratentorial leptomeningeal metastasis of a medulloblastoma without cerebellar tumor recurrence.

The authors report on a 15-year-old girl presenting with headache and nausea. Cranial magnetic resonance imaging (MRI) showed a diffuse leptomeningeal contrast enhancement 5 years after resection of a posterior fossa medulloblastoma followed by radio- and chemotherapy. A left frontal biopsy revealed tumor spread. Histopathological findings of the tumor were identical to those obtained from the original medulloblastoma. To the authors' knowledge this is the first report of late supratentorial leptomeningeal metastasis from a medulloblastoma while no local recurrence or spinal leptomeningeal dissemination had occurred.

Adolescent↗

Heavy ion RBE and microdosimetric spectra.

Reliable values for the relative biological effectiveness (RBE) of the complex field of heavy ions is essential for radiation therapy with carbon beams. Clinical experience with this novel form of therapy is still quite narrow and it is, therefore, desirable to compare and combine relevant clinical findings and theoretical approaches. One major source of available information comes from neutron therapy. The approach towards the determination of RBE for neutron therapy is, therefore, tentatively applied to the heavy ion therapy. This includes the determination of microdosimetric spectra and their numerical evaluation towards the determination of RBE. A microdosimetric detector on the basis of a tissue-equivalent proportional counter (TEPC) was developed for measurements in the heavy ion fields of the GSI, Darmstadt. Measurements were performed first near the perspex phantom surface with carbon ion energies between 89 MeV.amu-1 and 430 MeV.amu-1. Subsequently, measurements were taken at various depths in the neighbourhood of the Bragg region. The numerical techniques that were developed for neutron therapy lead to tentative values of the RBE that are compared to the RBE values from the biophysical model developed at the GSI. The comparison is still preliminary but can be helpful in modifying the microdosimetric approach for its application in heavy ion therapy.

Equipment Design↗

Phosphatidylcholine does not protect rats against 5-fluorouracil/folinic acid-induced damage of the intestinal luminal mucosa.

PURPOSE: The study was performed to evaluate the ability of phosphatidylcholine (PPC) to modulate the toxicity of 5-fluorouracil/folinic acid (5-FU/FA) in rats. METHODS: Twenty-eight female Wistar rats were divided into four series, each consisting of 6--8 animals and administered 0.5 ml isotonic solution i.v. once a day. The series were as follows: 1) saline; 2) 20 mg 5-FU + 4 mg FA; 3) 30 mg 5-FU + 6 mg FA; 4) 2 weeks daily orally 50 mg PPC/kg body weight (b.w.), on day 12, 30 mg 5-FU + 6 mg FA. As an indicator of membrane luminal impairment, 72 h after an i.v. administration, peptidase activities were measured by using an in situ perfusion model. RESULTS: The i.v. application of 5-FU/FA causes a clear reduction of enzyme activities in comparison to the control group. CONCLUSIONS: In investigations with rats, we have shown that a low concentration of oral PPC (50 mg/kg b.w.) cannot protect the luminal mucosa membrane from being injured by the enterotoxic action of 5-FU/FA.

Administration, Oral↗

[Mechanical changes in bone after roentgen irradiation with low dosage].

We investigated the micromechanical properties using doses from 1 up to 7 Gray and could observe a roughening on the surface of the bone material in the microscopic range by scanning acoustic microscopic measurements. In addition, a preceding irradiation promoted an extension of microcracks during the polishing process indicating an embrittlement. After irradiation and removal of the surface layer, the SAM measurements indicate a preferential increasing of hardness of softer regions. These results are consistent with our measurements by environmental scanning electron microscopy.

Aged↗

A low dose of ionizing radiation increases luminal release of intestinal peptidases in rats.

PURPOSE: Mucosal inflammation in the small intestine is a potentially hazardous side effect of abdominal irradiation. In an effort to develop a quantitative method of evaluating mucosal damage, the luminal release of brush border enzymes in response to ionizing radiation was examined using two investigational strategies. METHODS: First, a 20 cm segment of the proximal jejunum was perfused in situ and enzymatic activities within the perfusates were evaluated. In a second approach, enzymatic activities were directly evaluated in isolated brush border membranes from the jejunal mucosa. RESULTS: Most of the peptidase activities measured were increased in the perfusates 1 day after irradiation and had returned to control levels at 4 days. In the brush border membranes, some enzyme activities decreased at 1 day and were, with the exception of leucineaminopeptidase (LAP), similar to control levels at 4 days. CONCLUSIONS: LAP is more strongly affected by radiation than the transmembranously bounded enzymes.

Animals↗

Protective effect of oral phosphatidylcholine on radiation-induced release of intestinal peptidases in rats.

PURPOSE: To investigate whether phosphatidylcholine (PPC) has a protective effect on mucosa-irradiated rats. METHODS: The rats were orally fed with 25, 50, and 100 mg PPC/kg body weight (b.w.), respectively, for 3 weeks before irradiation. After administering the medication and 1 day after irradiation, a 20 cm segment of the proximal jejunum was perfused in situ and peptidase activities, as well as the concentrations of the membrane components, were assayed. RESULTS: We have shown that the application of a low dose of 25 mg PPC/kg b.w. daily for 21 days can prevent damage to membranes induced by 2.0 Gy as represented in the peptidase release profiles during the perfusion of the proximal jejunum of rats. Higher dose levels did not increase the protective effect. CONCLUSIONS: These findings suggest that a low dosage of exogenous PPC is capable of hindering the impairment of membranes induced by a small dose of radiation.

Administration, Oral↗

The risk of haemorrhage associated with early postoperative heparin administration after intracranial surgery.

BACKGROUND: To analyse the rate of postoperative haemorrhage during a 4-year period of early postoperative administration (< 24 hours) of fractionated heparin plus compression stockings in a large cohort of patients undergoing intracranial surgery. METHOD: A total of 1564 patients who underwent intracranial surgery at our institution were included in our study. 1197 of the 1564 patients (77%) had major intracranial surgery (group 1). Group 2 was made up of 367 patients in whom ventriculoperitoneal shunting or external ventriculostomy was performed (minor intracranial procedures). All patients were investigated retrospectively for the occurrence of major postoperative haemorrhage confirmed by CT scanning and requiring surgical evacuation. The protocol for prophylaxis of thrombo-embolic events included early (< 24 hours) postoperative fractionated low-dose heparin (3 x 5000 IE subcutaneously) until discharge plus intra- and postoperative compression stockings. FINDINGS: Major postoperative haemorrhages were observed in 31 of the 1564 patients (2.0%). In three patients, the haemorrhage occurred on the day of surgery before the administration of heparin. The haemorrhage rate of patients receiving heparin was 1.8% (28/1564). All haemorrhages occurred in patients undergoing major intracranial procedures (group 1; 31/1197; 2.6%). There was no haemorrhage in minor intracranial procedures (group 2; 0/367; 0%). INTERPRETATION: Although retrospective, this is to date the largest study supporting the concept of postoperative pharmacological thrombo-embolic propylaxis in patients undergoing intracranial surgery. The question as to whether pharmacological prophylaxis is beneficial for a given patient can only be answered by weighing the risk reduction of thrombo-embolic events against the risk increase of postoperative haemorrhage associated with different surgical procedures and heparin protocols.

Adolescent↗

Intervertebral disc calcification in childhood--a case report and review of the literature.

The authors report the case of a 10-year-old girl with intervertebral disc calcifications from the levels C6/C7 to Th1/Th2, presenting with a herniated calcified intervertebral disc at the C7/Th1 level, causing spinal cord compression with subsequent progressive paresis and sensory loss of her left leg. After anterior cervical discectomy and fusion the neurological deficits completely resolved within 2 weeks. It can be concluded that calcification of an intervertebral disc is a rare syndrome in childhood, causing progressive neurological deficit only in a few reported cases. Although the treatment of choice is conservative, surgery is required in patients who develop progressive neurological deficit.

Calcinosis↗

Factor XIII deficiency and postoperative hemorrhage after neurosurgical procedures.

BACKGROUND: Factor XIII is of physiological importance for hemostasis, especially in patients undergoing surgery. It catalyzes the enzymatic cross-linking of fibrin monomers into stable polymers and protects polymers from plasmatic and nonspecific degradation. Postoperative hemorrhage in patients with congenital and acquired Factor XIII deficiencies has been described in various surgical fields. However, there are no data about the incidence and clinical relevance of decreased Factor XIII after neurosurgical procedures. The objective of our study was to investigate the association between Factor XIII deficiency and postoperative hemorrhage after intracranial surgery. METHODS: A total of 1264 patients who underwent intracranial operations were reviewed retrospectively. Standard coagulation parameters were monitored during the perioperative course in all patients. Factor XIII testing was performed postoperatively in 34 patients in whom coagulopathies were suspected despite normal platelets, fibrinogen, prothrombin, and partial thromboplastin time. Data were analyzed to evaluate the association of Factor XIII deficiency and major postoperative hemorrhage. RESULTS: In this series of 1264 patients, a total of 20 patients (1. 6%) suffered from a major postoperative hemorrhage. Of the 34 patients with suspected coagulopathies and postoperative Factor XIII testing, 11 had a major postoperative hemorrhage. Normal levels of Factor XIII, defined as more than 60%, were found in 26 of the 34 patients. Factor XIII deficiency, defined as less than 60%, was found in eight patients. All patients with Factor XIII deficiency (n = 8) had a major postoperative hemorrhage. Of the remaining 26 patients with normal Factor XIII levels only three had a postoperative hemorrhage (p < 0.00001, Fisher's exact test). CONCLUSIONS: Decreased Factor XIII activity may be associated with an increased risk of postoperative hemorrhage after intracranial surgery.

Adult↗

[Practice of perioperative thromboembolic prophylaxis in neurosurgery: results of a German survey].

Many neurosurgical patients are at high risk of developing thromboembolic disease. Although recent data support the benefit of pharmacological thromboembolic prophylaxis, the optimal starting point for the different neurosurgical procedures remains unclear because the potentially devastating consequences of intracranial or intraspinal haemorrhage could easily offset the reduction in thromboembolic morbidity and mortality resulting from pharmacological thromboembolic prophylaxis. The objective of our study was to assess the use of pharmacological methods of thromboembolic prophylaxis in contemporary German neurosurgery using a postal survey in 34 neurosurgical departments. Low-dose heparin or low molecular weight heparin (LMWH) were used in 88% to 97% of neurosurgical units participating in our survey. In craniotomies, in 2 units (6%) heparin or LMWH was routinely started before surgery, in 10 units (29%) < 8 hours after surgery, in 15 units (44%) < 24 hours after surgery, in one unit at the second day and in 5 units at the third day after surgery. Data for burr hole craniotomy or spinal surgery were similar. In our survey a high rate of perioperative use of pharmacological thromboembolic prophylaxis was found. However, given the data from the literature, the optimum protocol remains unclear.

Anticoagulants↗

Cerebellopontine angle lipoma: case report and review of the literature.

Intracranial lipomas located in the cerebellopontine angle are extremely rare. These tumours are mal-developmental lesions which can cause slowly progressive neurological symptoms. The clinical management of these tumours differs significantly from other lesions in this region. A 27 year old woman presented with a 2-month history of vertigo and a slowly progressive deterioration of hearing in the left ear. Computed tomography (CT) revealed a large low-density mass in the left cerebellopontine angle without any contrast-enhancement. In T1-weighted magnetic resonance imaging (MRI) the lesion was hyper-intense and did not enhance after application of gadolinium. Areas of lower signal intensity inside of the lesion were suggested as incorporated cranial nerves. A left retro-sigmoidal approach in a semi-sitting position was chosen to expose the tumour. After reducing the tumour mass, the tumour was dissected from the cranial nerves which were incorporated into the tumour. The residual tumour was adherent to the brain stem and the encased lower cranial nerves, allowing only a near subtotal resection of the highly vascularized tumour in order to avoid neurological deficits. The histological examination revealed a lipoma. Attempts at complete removal of cerebellopontine angle lipomas usually result in severe neurological deficits. Conservative treatment should therefore be preferred. Limited surgery is indicated if the patients suffer from disabling neurological symptoms and signs e.g., vertigo, nausea, trigeminal neuralgia, facial weakness or facial spasm.

Adult↗