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Biomedical subjects

D Lindner

Publications and source records attributed to D Lindner.

At least 19 recordsLinked to original sources

Surgery of cavernous malformations with and without navigational support--a comparative study.

BACKGROUND: The aim of this descriptive study was the comparison of the clinical and surgical data of patients who suffered from cavernoma and were treated surgically with and without intraoperative navigation (ultrasound, neuronavigation). METHOD: Between 1995 and 2002, 40 patients were treated for cavernous malformations microsurgically: 24 patients (group I) using a neuronavigation system (STP 4.0, SNN, Germany), 7 patients (group II) using ultrasound (Siemens Omnia with 5.0 MHz Probe) and 9 patients (group III) without any image guidance using anatomic landmarks. FINDINGS: With the use of neuronavigation the mean sizes of cavernous malformations, which were resected, were reduced from 25.6 mm (group III) and 24.4 mm (group II) to 16.3 mm (group I) (p > or = 0.05). Corresponding to the reduction of the cavernoma size, the mean distances of the vascular lesion to the cortical surface increased from 13.9 mm (group III) and 17.8 mm (group II) to 24.4 mm under neuronavigational support (p > or = 0.05). All cavernomas were resected completely in all 40 patients. Postoperative neuroradiological control (MRI) confirmed complete resection in all cases. No significant differences in the clinical outcome could be evaluated in all three groups up to three months postoperatively. CONCLUSIONS: Use of neuronavigation was associated with a more comfortable and safer surgery of smaller and more deeper-seated cavernomas. In spite of the lack of significance between all groups, the advantages of neuronavigation in planning and realising surgery could be documented, which justify the additional costs and time-consuming acquisition of planning image data and postprocessing as well as intraoperative navigation.

Adolescent↗

Application of intraoperative 3D ultrasound during navigated tumor resection.

Intraoperative 3D ultrasound (3D-iUS) may enhance the quality of neuronavigation by adding information about brain shift and tumor remnants. The aim of our study was to prove the concept of 3D ultrasound on the basis of technical and human effects. A 3D-ultrasound navigation system consisting of a standard personal computer containing a video grabber card in combination with an optical tracking system (NDI Polaris) and a standard ultrasound device (Siemens Omnia) with a 7.5 MHz probe was used. 3D-iUS datasets were acquired after craniotomy, at different subsequent times of the procedure and overlaid with preoperative MRI. All patients underwent early postoperative 3D MRI including contrast agent within 24 hours after surgery. Acquisition of 3D iUS and the fusion with preoperative MRI was successful in 22/23 patients. The expenditure of time was at least 5 minutes for one intraoperative 3D US dataset. The technique was used three to seven times during surgery. The quality of the ultrasound images was superior in cases of metastasis, meningeoma and angioma over those in malignant glioma. Brain shifting ranged from 2-25 mm depending on localization and kind of tumor. A resection control was possible in 78%. All six neurosurgeons demonstrated a learning curve. The introduction of 3D ultrasound has increased the value of neuronavigation substantially, making it possible to update several times during surgery and minimize the problem of brain shift. Configuration of both the 3D iUS based on a standard ultrasound system and the MR navigation system is time- and especially cost-effective. Faster navigational datasets and more intuitive image-guided surgery enable novel and user-friendly display techniques.

Adult↗

Assessment of ventricular reconfiguration after third ventriculostomy: what does shape analysis provide in addition to volumetry?

PURPOSE: From neuroradiologic experience, it is evident that the adaptation of the ventricular system secondary to pathologic processes or surgery is not uniform. To describe changes entirely, one must consider, in particular, information about volume and shape. In this study, we address specifically the information encoded in the change of shape. To exemplify the technique, we used time-series MR imaging examinations of patients with surgically treated chronic or acute occlusive hydrocephalus. METHODS: Preoperative and postoperative MR imaging at different time-steps was performed in 2 patients with occlusive hydrocephalus with a different time course of ventricular enlargement. The third and lateral ventricles were segmented with an automated classification scheme. Ventricular surfaces were binarized, mapped to a spheric coordinate system, and modeled by harmonic-basis functions. This approach allows simplification of the complex shape by stepwise filtering of the details that form the surface. The ventricles can be directly compared on the level of the simplified shape. RESULTS: Although the relative volumetric change was comparable between patients, analysis of shape revealed notable regional differences in the pattern of adaptation. Comparing subacute and chronic hydrocephalus, the analysis reflected fundamental differences in the pattern of ventricular enlargement. CONCLUSION: In addition to the mere volumetric description, this approach identifies regions that re-adjust differently to the altered pressure. The pattern of re-adaptation depends on the time course and history of the hydrocephalus. Furthermore, the different patterns of ventricular adaptation in patients with chronic or subacute hydrocephalus suggest a contiguity with properties of the surrounding parenchymal tissue.

Adult↗

Effect of 3T MRI on the function of shunt valves--evaluation of Paedi GAV, Dual Switch and proGAV.

The MR-compatibility of medical implants and devices becomes more and more important with the increasing number of high-field MR-scanners employed. Until the end of 2004, about twenty 3T MR in Germany will be in clinical practice. Patients with hydrocephalus need frequent follow-up MR-examinations to assure correct functioning of a shunt. We tested three types of gravitational valves: the Paedi GAV, the Dual Switch and as a new programmable valve the proGAV (Miethke Company, Berlin), that have not been evaluated at 3T, yet. In sum, there is strong evidence for maintenance of function of these valves after exposure to 3T. This also implies the programmable valve, as long as the brake mechanism is properly adjusted during MR-examination.

Cerebrospinal Fluid Shunts↗

Evaluation of intra-operative ultrasound imaging in brain tumor resection: a prospective study.

AIMS: The purpose of our study was to evaluate intra-operative ultrasound (IOUS) as a tool of resection control after brain tumor surgery. In addition, we looked for tumor species suitable for ultrasound representation. METHODS: Using a Siemens Omnia Sonoline Ultrasound, 36 tumors were examined, high-grade gliomas (62%), metastases (22%) and others (16%). We focused on tumor imaging by ultrasound with regard to its reliability of tumor expansion and margins. Evaluation of the images was carried out by correlating the ultrasound-based intra-operative measured tumor volume before and after resection with a pre- and post-operative (within 48 hours) measured volume by MRI. The IOUS measurements were performed by the neurosurgeon and the MRI measurements by the neuroradiologist. Thus, the measurement procedures were blinded. Corresponding to a deviation of the ultrasound volume by 10, 20 and > 20% from the MRI volume, the correlation was ranked good, moderate and poor. For assessing the agreement between these two methods of imaging, the statistical analysis was conducted using a method described by Bland and Altman. RESULTS: High-grade gliomas mostly showed a moderate or poor correlation in comparing IOUS- and MRI-tumor volumetry resulting in incomplete resection. Metastases resulted in a good to moderate correlation with a satisfactory extent of resection. The other tumors had poor images with larger tumor residues. The MRI measured volumes tended to be larger on average; the deviation grew with tumor size . CONCLUSION: The reliability of IOUS depends on tumor type. It is beneficial to use IOUS for the resection of metastases and a few high-grade gliomas. Concerning the volumetric accuracy, the value of IOUS is worse than its value of navigation and resection control.

Adolescent↗

Cavernous malformations--navigational supported surgery.

OBJECTIVE: Navigational supported surgery of intracranial lesions is expected to be associated with a lower rate of brain traumatization as well as an avoidance of additional neurological deficits and surgical morbidity. In our study we used the computer-assisted image guidance for resection of cerebral cavernous malformations. METHODS: In all patients the planning procedure for the following image-guided surgery was realized using preoperative MRl data sets and a neuronavigation system (STP 4.0, SNN). In cases in which the cavernoma was situated near functional eloquent regions, functional MR images were fused preoperatively. RESULTS: During the last 24 months, 21 patients were surgically treated for cerebral cavernoma. No patient was operated twice. The mean size of cavernoma was 18.3 mm, ranging from 5 to 60 mm, the mean distance between cortical surface and cavernoma was 26 mm, ranging from 5 to 50 mm. The surgical procedure lasted in the median 180 min. All patients showed an identical or better neurological outcome. CONCLUSIONS: Neuronavigation allows an accurate definition of the intraoperative target, a correct approach and a safe surgery. With the help of neuronavigation the surgical approach and the extirpation of cavernous malformations were realized in a comfortable and safe way and allowed a minimization of tissue manipulation.

Adolescent↗

Prevalence of extra-oesophageal manifestations in gastro-oesophageal reflux disease: an analysis based on the ProGERD Study.

BACKGROUND AND AIMS: Gastro-oesophageal reflux disease (GERD) can be associated with a variety of extra-oesophageal disorders (EED) such as chronic cough, asthma, laryngeal disorder or chest pain. The aim of the study was to estimate and compare the prevalence of EED in a population with symptomatic GERD presenting as either erosive reflux disease (ERD) or non-erosive reflux disease (NERD). METHODS: Baseline data were collected from a prospective, multicentre, open cohort study (ProGERD) in which patients will be followed for 5 years after initial treatment with esomeprazole. Within the framework of this trial, all patients underwent gastroscopy and filled out a questionnaire designed to assess EED. The influence of potential prognostic factors on the prevalence of EED was analysed by multivariate (stepwise logistic regression) analysis. RESULTS: 6215 patients (3303 male, 2912 female; mean age 54 years) presenting with heartburn were included. EED was detected in 32.8% of all patients. The proportion was significantly higher (P = 0.0002) in ERD patients (34.9%) than in NERD patients (30.5%). As judged from the multivariate analysis, female gender, age, oesophagitis of LA grade C/D, duration of GERD disease greater than 1 years and smoking were significantly associated with EED. ERD patients with oesophagitis of LA grade A or B did not have a significantly higher risk of EED than patients with NERD. CONCLUSIONS: Patients with GERD have a high probability of experiencing EED, which may be associated with a number of prognostic factors such as duration and severity of GERD. Extra-oesophageal disorders are slightly, but statistically, more prevalent in ERD than in NERD patients.

Asthma↗

Clinical results in MR-guided therapy for malignant gliomas.

The prognostic impact of the extent of tumour resection in surgery of malignant glioma patients remains controversial. We report the results of cumulative survival of malignant glioma patients operated with MR-guidance. Patients with complete tumour removal were compared with a population of patients with incomplete tumour removal. A 0.5 T scanner was used to criticize the extent of resection during surgery. In total no significant difference could be found, however there is a tendency that complete tumour removal seems to be associated with a slightly increased median survival time.

Adult↗

Improving planning procedure in brain biopsy: coupling frame-based stereotaxy with navigational device STP 4.0.

37 consecutive patients with space-occupying intracerebral lesions were operated via frame-based stereotaxy. After CT-localizing of suspect lesions and computer-supported definition of entry and target coordinates a serial stereotactic biopsy was performed. Biopsy specimens allowed a satisfactory neuropathological examination and diagnostic result in 36 cases (97 %). Only three patients (8.1 %) showed an intraoperative bleeding, which was not associated with any postoperative CT-detectable hematoma, neurosurgical intervention nor with any neurological deficits. In summary we described the method of a computerized planning technique for stereotactic biopsy with the use of a special stereotactic planning program. High percentage of satisfactory neuropathological diagnoses and comfortable and accurate definition of target and entry coordinates justify computer support as a routine method.

Adolescent↗

Second-generation interferons for cancer: clinical targets.

IFNs were the first new therapeutic products resulting from recombinant DNA technology. IFNs were also the first human proteins effective in cancer treatment. There is however much to be discovered which will lead to new clinical applications. Areas which represent major research challenges for full understanding and application of the IFN system are: (i) the diversity of the IFN family; (ii) the role of induction; (iii) molecular mechanism of action; (iv) cellular modulatory effects; (v) advantages of combinations, and (vi) identification of new therapeutic indications. This review will emphasize the diversity of the IFN family and chemical modifications which will result in second-generation IFNs. Pre-clinical and clinical findings form the basis for new therapeutic directions in chronic myelogenous leukemia, lymphomas, myelomas, melanoma, urologic malignancies, primary brain tumors, and ovarian carcinoma.

Animals↗

RAG mutations in human B cell-negative SCID.

Patients with human severe combined immunodeficiency (SCID) can be divided into those with B lymphocytes (B+ SCID) and those without (B- SCID). Although several genetic causes are known for B+ SCID, the etiology of B- SCID has not been defined. Six of 14 B- SCID patients tested were found to carry a mutation of the recombinase activating gene 1 (RAG-1), RAG-2, or both. This mutation resulted in a functional inability to form antigen receptors through genetic recombination and links a defect in one of the site-specific recombination systems to a human disease.

B-Lymphocytes↗

Lack of an effect of novel inhibitors with high specificity for protein kinase C on the action of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate on mouse skin in vivo.

The inhibitory effects of three novel staurosporine-derived compounds were tested with five different types of protein kinases, including protein kinase C (PKC). IC50 values of two of these compounds were found to be 300 to > 5000 times lower for PKC alpha beta gamma (a mixture of the PKC isoenzymes alpha, beta and gamma) than for any of the other protein kinases. The inhibitory action of the most selective inhibitor was tested also with the Ca(2+)-unresponsive PKC isoenzyme delta and was found to suppress PKC alpha beta gamma and PKC delta differentially. The highly specific PKC inhibitors are active both in cell culture and in vivo. They inhibit the PKC-catalyzed phosphorylation of the specific PKC substrate MARCKS in Swiss-3T3 fibroblasts and the okadaic acid-induced edema of the mouse ear. However, the more complex biological processes triggered by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate in mouse skin, such as inflammation, stimulation of cellular hyperproliferation and tumor promotion, remain largely unaffected upon topical application of these compounds.

3T3 Cells↗

Urban Schistosoma mansoni near Enyau river in Arua town, Uganda.

Using the Kato Katz method for quantification of parasitic eggs in faeces, 500 individuals aged between 4 and 50 years, living along River Enyau, half a kilometre from Arua town, were studied to assess the prevalence of Schistosoma mansoni in the population. The overall prevalence of Schistosoma mansoni infection was 62%. The infection was highest among school children (71.1%, i.e. 199 out of 280). Villagers who lived along the immediate vicinity of the river had a 62.8% prevalence of infection (98 out of 156). School teachers and the members of their families had the lowest infection rate (20.3% i.e. 13 out of 64). The geometric mean egg output for males and females in the community studied was 203 and 179 eggs per gram of stool, respectively. 206 (41%) out of 500 individuals had mixed infections of S. mansoni and hookworms. The rate of orally transmitted intestinal helminths like Trichuris trichiura was very low (0.8%). Ascaris lumbricoides eggs were not found.

Adolescent↗

Transmission of Schistosoma mansoni in Rhino Camp, Uganda.

Non-participant observations totalling 204 hours relevant to the transmission of Schistosoma mansoni infection were carried out in Rhino Camp at the shores of Albert Nile in North Uganda. A cross-sectional study of 636 individuals from Rhino Camp revealed a prevalence of S. mansoni infection of 77.8%. Occupational and domestic purposes were the most important reasons for water contact, whereas recreational purposes ranked lower and mainly concerned children. Both sexes were equally active in water contacts. A distinct preference of Nile water was noted despite availability of borehole water in the area. It is concluded that control measures against schistosomiasis have to take into consideration that water contact for recreational purposes might be minimized, whereas it is expected to be extremely difficult to reduce occupational and domestic water contacts.

Adult↗

Failure to improve height prediction in short-stature pubertal adolescents by inhibiting puberty with luteinizing hormone-releasing hormone analogue.

A group of 17 endocrinologically normal short stature adolescent (9 females aged 11.8 +/- 1.5 years and 8 males aged 13.2 +/- 1.1 years) referred at a pubertal stage II-III according to Tanner with a height prediction below -2.5 SD according to Bayley and Pinneau, were treated with long-acting D-Trp6-luteinizing hormone-releasing hormone (3.75 mg i.m. monthly for 24 months) and observed for a period of 13.4 +/- 5.8 months. Pubertal progression was suppressed during the 2 years of analogue therapy, then resumed shortly after the end of treatment. Annual growth rate remained in the prepubertal range during the treatment period and did not increase with the resumption of sexual development. A reduced rate of bone maturation was observed during the 2 years of analogue treatment without clear-cut improvement of the height to bone age relationship at the end of the treatment nor after the post-treatment observation period. Thus, after approximately 3 years of study, no significant improvement of predicted adult stature was obtained. There were no side-effects, but psychological problems mainly related to the failure to increase height. Though methods for predicting adult height are not accurate, these data suggest that use of luteinizing hormone-releasing hormone analogue in endocrinologically normal short subjects entering puberty at normal age with a poor height prognosis does not offer enough possible advantages on growth to offset the possible psychological drawbacks, and cannot be considered as routine treatment in this situation.

Adolescent↗

Differential inhibition by staurosporine of phorbol ester, bryostatin and okadaic acid effects on mouse skin.

The tumor promoters 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a strong activator of protein kinase C (PKC) and okadaic acid, which is ineffective in this respect, induce a rapidly developing ('early') edema of the mouse ear. Bryostatin, another potent activator of PKC, is unable to induce an 'early' edema but causes a more delayed development of edema at a time when most of the PKC is down-regulated. The PKC inhibitor staurosporine neither inhibits the early TPA- nor the late bryostatin-induced edema, but suppresses the okadaic acid-induced edema very effectively. TPA as well as bryostatin, but not okadaic acid cause a down-regulation of PKC, which is not inhibited by staurosporine. The calmodulin antagonist cyclosporine A, which does not suppress PKC activity, very effectively inhibits the TPA-induced edema and down regulation of PKC. Hence we conclude that protein phosphorylation catalyzed by staurosporine-suppressable PKC is not involved in the induction of edema and PKC down-regulation by TPA but that a calmodulin dependent process may play a critical role in these and other TPA effects in mouse skin.

Alkaloids↗

Phorbol ester-induced down-regulation of the 80-kDa myristoylated alanine-rich C-kinase substrate-related protein in Swiss 3T3 fibroblasts. Inhibition by staurosporine.

A polyclonal antiserum raised against an oligopeptide with an amino acid sequence corresponding to a sequence of the myristoylated alanine-rich C-kinase substrate (MARCKS) from mouse macrophages and rat brain recognizes the 80-kDa C-kinase substrate from Swiss 3T3 fibroblasts. Using this antiserum for quantitative determination of the 80-kDa MARCKS-related protein, we found that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a rapid down-regulation of this protein in the fibroblasts. In accordance with earlier reports, TPA causes phosphorylation of the 80-kDa protein which can be inhibited by staurosporine. Staurosporine also suppresses the TPA-induced down-regulation, possibly indicating that the down-regulation of the MARCKS-related protein is dependent on its phosphorylation by protein kinase C.

3T3 Cells↗