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Biomedical subjects

M Kiefer

Publications and source records attributed to M Kiefer.

At least 19 recordsLinked to original sources

Gravitational valves: relevant differences with different technical solutions to counteract hydrostatic pressure.

Two different technical principles of gravitational valves (G-valves) have been presented: counterbalancer and switcher G-valves. The objective of our prospective study was to look for clinically relevant differences between both. A total of 54 patients with normal-pressure hydrocephalus (NPH) were treated; 30 patients received an Aesculap-Miethke GA-Valve (GAV; counterbalancer), and in 24 patients an Aesculap-Miethke Dualswitch-Valve (DSV; switcher) was implanted. The opening pressure of the posture-independent valve was 5 cm H2O in both devices. The outcome was clearly better with the usage of the GAV than with the DSV. The frequency and severity of complications was pronounced in the DSV group. We recommend the Aesculap-Miethke-GAV valve with a low opening pressure in a posture-independent valve for patients with NPH.

Adult↗

On the optimal opening pressure of hydrostatic valves in cases of idiopathic normal-pressure hydrocephalus: a prospective randomized study with 123 patients.

Does the opening pressure of hydrostatic shunts influence the clinical outcome for patients suffering from idiopathic normal-pressure hydrocephalus (NPH)? Between September 1997 and January 2003, 123 patients with idiopathic NPH were surgically treated by implanting a hydrostatic shunt at the Departments of Neurosurgery of the Unfallkrankenhaus Berlin and the University Homburg/Saar. As part of a prospective randomized study, all patients were examined preoperatively, postoperatively, and 1 year after the intervention. Forty-three percent of the patients showed a very good outcome, 25% good outcome, 20% fair outcome, and 12% poor outcome 1 year after the shunt implantation. Patients treated with an opening pressure rating of 50 mmH2O in the low-pressure stage of the gravitational valve showed a better outcome than those with an opening pressure of 100 or 130 mmH2O. According to present knowledge, hydrostatic shunts with an opening pressure of 50 mmH2O for the low-pressure stage are the best option for patients with idiopathic NPH. Due to the prompt switching function when the patient changes posture (lying down, standing, sitting, slanting etc.), the Miethke gravity-assisted valve (GAV) is more suitable in such cases than the Miethke Dual-Switch valve (DSV).

Adult↗

Outcome predictors for normal-pressure hydrocephalus.

The objective of this prospective study was to find outcome predictors for better selection for treatment of normal-pressure hydrocephalus (NPH) patients. A total of 125 patients were evaluated and provided with a gravitational shunt. Cerebrospinal fluid hydrodynamics provided better predictive values if an algorithm to shunt all patients with a pressure/volume index of < 30 mL or resistance to outflow > 13 mmHg/mL x min was used. In general, outcome became worse with increasing anamnesis duration, worse preoperative clinical state, and increasing comorbidity. If one of these parameters was lower than a critical value, the shunt-responder rate was about 90% and the normally negative influence of older age was not seen. The well-known paradigm of a worse prognosis with NPH is not the result of the hydrocephalus etiology itself, but the consequence of a typical accumulation of negative outcome predictors as a consequence of the misinterpretation of normal aging and delayed adequate treatment.

Cerebrospinal Fluid Shunts↗

Gravitational shunt management of long-standing overt ventriculomegaly in adult (LOVA) hydrocephalus.

OBJECTIVES: Recently a new subtype of chronic hydrocephalus was described: long-standing overt ventriculomegaly in adults (LOVA). Experience to date has indicated that shunt therapy was contraindicated, due to over-drainage. Therefore we investigated whether this problem could be overcome using gravitational shunts. MATERIALS AND METHODS: Thirty macrocephalic adults (17-72 years of age), suffering from progressive hydrocephalus were managed with two different gravitational shunts. The post-operative observation period was 5-87 months. RESULTS: Only two patients developed hygromas, and only one of these required surgical shunt revision. Eighty-seven percent of patients had a long-lasting clinical improvement. Ventricular size was only slightly reduced in 29 patients. There was no correlation between reduction in ventricular size and clinical improvement. CONCLUSION: Contrary to clinical guidelines issued to date, we demonstrate that LOVA can be treated reliably with gravitational shunts, making them a genuine alternative to endoscopic third ventriculostomy (ETV).

Adolescent↗

Does the pattern of atrophy of the Corpus callosum differ between patients with frontotemporal dementia and patients with Alzheimer's disease?

The pattern of callosal atrophy might be useful for the differentiation between frontotemporal dementia (FTD) and Alzheimer's disease (AD) in advanced cases. However, it is unclear whether the pattern of callosal atrophy differs between patients with FTD and patients with AD in mild to moderate stages. Volumetric MR images were recorded from 48 probands (12 with FTD, 12 with late-onset AD, and 24 controls). All patients were in a mild or in a moderate stage. The corpus callosum was divided into five segments. A repeated-measures analysis of variance showed that there was no difference in the pattern of callosal atrophy between the groups. We provide evidence that patients with FTD and patients with late-onset AD do not differ in the pattern of callosal atrophy on condition that: (1) FTD patients and AD patients are in a mild to moderate stage and (2) FTD patients and AD patients differ in age.

Aged↗

Review about Ginkgo biloba special extract EGb 761 (Ginkgo).

Ginkgo biloba extracts (EGb) are well-defined plant extracts. It has several indications as dementia, macula degeneration, tinnitus and winter depression. A review of the current and past literature about older people with Alzheimer's dementia or vascular dementia or age-associated memory impairment treated with Ginkgo biloba extract, reveals that EGb has reproducible effects on cognitive functions in Alzheimer's disease. The drug is well tolerated.

Alzheimer Disease↗

The ICP-dependency of resistance to cerebrospinal fluid outflow: a new mathematical method for CSF-parameter calculation in a model with H-Tx rats.

The international accepted calculation methods concerning the cerebrospinal fluid dynamics proceed from a pressure independent resistance to cerebrospinal fluid outflow. In a new model we focus our attention on the pressure dependency of resistance. In our calculation model we are monitoring the complete pressure course p(t) over the time t during and after the infusion. The comparison of the pressure rise On(p) during the infusion and the descent Off(p) after the infusion in the same pressure level allows to construct all formulas for the compliance C(p) and resistance R(p). The simultaneous measurement of the resistance and complications during a single investigation allows minimizing the patient's exertion. In contrast to the classical methods it is not necessary that the ICP reach a plateau. Our mathematical method diverges with the description of a pressure dependent slope of the function for the resistance from the static examination models. We proved our mathematical method by the use of a dynamic infusion test in ten H-Tx rats without hydrocephalus and five hydrocephalic H-Tx rats. For that we are able to take the non-linearity of the CSF resorption into consideration.

Animals↗

[A systematic comparison of national and international dementia guidelines].

Several guidelines for the evidence-based diagnosis and treatment of dementing disorders have been published in Germany and worldwide during the last years. This review analyses the content and methodological quality of 13 recently published dementia guidelines. There are some unequivocal recommendations for diagnostic procedures (e. g. clinical evaluation, neuropsychological screening, structural brain imaging) and treatment (e. g. cholinesterase inhibitors). There is a broad range of opinions on other procedures (e. g. routine EEG, FDG PET, cognitive training). A discussion of the prevalent guideline pluralism and a pleading for regionally adapted international guidelines conclude this article.

Dementia↗

[A grading system for chronic hydrocephalus].

A generally accepted grading system for patients suffering from chronic hydrocephalus has not been established yet. Therefore we designed a new grading system, which focuses on five symptom categories: gait disturbances, mental disorder, incontinence, headache, dizziness. For each category clearly circumscribed degrees of handicaps are defined. For each degree a value between 0-6 points is assigned in concordance to the severity of handicap. To get a generally accepted validation of the obstruction, the assigned values were oriented on the values provided in Germany to evaluate the degree of obstruction for insurances.[nl]In contrast to the established gradings of Stein and Langfitt and the Black Rating Scale our grading allows a more exact acquisition of the clinical presentation of a patient. Our experiences with the grading seemingly indicate also, that it is reliable. Because the grading allows an incorporation of measurable data such as psychometric analysis or gait analysis, our grading is useful as well for everydays' practice as for scientific purpose.

Chronic Disease↗

Arithmetic fact retrieval and working memory in schizophrenia.

Despite its importance in every-day life and vocational rehabilitation, arithmetic ability has rarely been investigated in schizophrenic patients. Those few studies reporting arithmetic deficits in schizophrenia, however, administered complex calculation tasks which drew not only on arithmetic abilities, but also on working memory resources known to be impaired in schizophrenia. In the present study, arithmetic abilities and working memory functions were investigated in schizophrenic patients (n=24) and healthy control subjects (n=24). Arithmetic fact retrieval was assessed in single-digit multiplication and corresponding division problems using a result verification task which minimized working memory demands. Problem size and the disparity of the proposed result were manipulated. The storage component of working memory was tested with a digit span forward task and the executive control component with a digit span backward as well as with verbal fluency tasks. Schizophrenic patients performed worse than controls only in the executive tasks. Digit span forward was preserved. In the arithmetic tasks, groups did not differ from each other, and a similar pattern of task manipulations was obtained. Hence, despite the executive control deficit retrieval of arithmetic facts is preserved in schizophrenia. Moreover, the same underlying cognitive processes as in control subjects are involved.

Adult↗

Online analysis of intracranial pressure waves.

Brain pressure waves, particularly B-waves, as they were described by Lundberg contain valuable diagnostic information about the patient's status. So far, this information cannot be used on a daily routine basis because manual analysis of the recorded ICP data is very time consuming. Furthermore, the analysis is only retrospective, after incidents of interest occurred. To overcome these drawbacks, an automated B-wave detection system has been developed. Using a direct spectral estimation method (so called ARMA approach) the most significant spectral components and their amplitudes in the ICP signal are identified. The frequency with the biggest amplitude inside the B-wave band is a reliable indicator of B-wave activity and can be displayed on-line on a bedside computer.

Humans↗

Multi-centre assessment of the Spiegelberg compliance monitor: interim results.

Analyses of a multi-centre database of 71 patients at risk of raised ICP showed that in head injured patients (n = 19) and tumour patients (n = 13) clear inverse relationships of ICP vs compliance exist. SAH patients (n = 5) appear to exhibit a biphasic relationship between ICP and compliance, however greater numbers of patients need to be recruited to this group. Patients with hydrocephalus (n = 34) show an initial decrease in compliance while ICP is less than 20 mmHg, thereafter compliance does not show a dependence upon ICP. A power analysis confirmed that sufficient numbers of patients have been recruited in the hydrocephalus group and a ROC analysis determined that a mean compliance value of 0.809 (lower and upper 95% CL = 0.725 & 0.894 resp.) was a critical threshold for raised ICP greater than 10 mmHg. Preliminary time-series analyses of the ICP and compliance data is revealing evidence that the cumulative time compliance is in a low compliance state (< 0.5 ml/mmHg), as a proportion of total monitoring time, increases more rapidly than the cumulative time ICP is greater than 25 mmHg. Before trials testing compliance thresholds can be designed, we need to consider not just the absolute threshold, but the duration of time spent below threshold. A survey may be required to identify a consensus of what is the minimum duration of raised ICP above 25 mmHg needed to instigate treatment.

Automation↗

[Modern intracranial pressure measurement techniques. Basic principles and general practice].

Measurement of intracranial pressure (ICP) has to be regarded as a standard procedure in today's treatment of severe head-injured patients. Intraventricular or intraparenchymal measurement should be used. The essential value for intensive care treatment is the cerebral perfusion pressure (CPP). Its value should be kept strictly > 70 mmHg. Computer-based analysis of the ICP-signal provides further options of an online monitoring of intracranial reserve capacity and the state of autoregulation. However, until now, there are no software solutions commercially available which would allow for such advanced signal analysis--the reason might be that the potential of advanced signal analysis has only been discovered within the recent years.

Adult↗

[LOVA hydrocephalus - a new entity of chronic hydrocephalus].

The recently defined term "longstanding overt ventriculomegaly in adults" (LOVA) describes a unique entity of chronic occlusive hydrocephalus. The experiences so far using conventional DP valves were not encouraging because of a high percentage of overdrainage. The objective was to evaluate whether gravitational shunts could be used for this condition with an acceptable overdrainage risk. Twenty-three macrocephalic adults aged 17-72 years suffered from chronic progressive hydrocephalic conditions. They received two different types of gravitational shunt. Follow-up ranged from 6 months to 75 months. Only two patients presented small subdural effusions postoperatively, and only one required additional treatment for that. Eighty-two percent were shunt responders. Ventricular size was only marginally reduced in 22 of the 23 patients. There was no correlation between clinical benefit and the reduction in ventricular size. Gravitational shunts clearly have the potency for safe treatment of LOVA, significantly reducing the risk of overdrainage over conventional valves, and may be considered an equivalent alternative to third ventriculostomy.

Adult↗

Five years experience with gravitational shunts in chronic hydrocephalus of adults.

OBJECTIVE: Gravitational shunts for management of chronic hydrocephalus are supposed to avoid or at least to reduce the risk of overdrainage. In order to find out if this hypothesis is correct, we did a prospective study and analysed the results of a series of 185 hydrocephalic adults, treated by using gravitational shunts. For the few cases in whom overdrainage occurred, we wanted to establish the reason for it. Especially it should be proven or excluded that overdrainage was caused by shortcomings of the principle of gravitational shunts. Another goal was to compare post-shunting changes of the ventricular size with clinical outcome. A comparably large study has not yet been published. METHODS: 185 adult patients who suffered from chronic hydrocephalus were shunted between 1996-2000, either using the combination of an adjustable Codmann Hakim Valve & Miethke Shunt Assistant (35 patients) or a Miethke Dual Switch Valve (150 patients). The clinical course of each patient has been followed until the end of 2000. Average follow-up time was 26 months (range 6-60 months). RESULTS: 88% of our patients were shunt responders, 70% had a good or excellent outcome. Overdrainage occurred in only 4%. It turned out that this complication was not a failure of the concept of gravitational shunts, but the result of a wrongly estimated intraperitoneal pressure. After shunting the ventricular size was reduced only marginally. In 92% of the patients the Evans-Index decreased less than 20% after the shunt insertion, but 69% of these patients had a good or excellent outcome. The most obvious difference comparing pre- and postoperative imaging was a better visibility of the high apical sulci after shunting. CONCLUSION: In our series gravitational shunts proved to be effective in preventing overdrainage. The 4% negative exceptions are mainly avoidable. There was no correlation between outcome and ventricular size reduction, and as a rule ventricular size was only marginally reduced.

Aged↗

The ICP-dependency of resistance to cerebrospinal fluid outflow: a new mathematical method for CSF-parameter calculation in a model with H-TX rats.

The international The simultaneous measurement of the resistance and compliance during a single investigation minimizes the patients exertion. In contrast to the classical method it is not necessary that the ICP reaches a plateau. Our mathematical method diverges with t he description of a pressure dependent slope of the function for the resistance from the static examination models. We proved our mathematical method by the use of a dynamic infusion test in 10 H-Tx rats without hydrocephalus and five hydrocephalic H-Tx rats. For that we are able to take the non linearity of the CSF resorption into consideration.

Animals↗

Metal ion binding and coordination geometry for wild type and mutants of metallo-beta -lactamase from Bacillus cereus 569/H/9 (BcII): a combined thermodynamic, kinetic, and spectroscopic approach.

One high affinity (nm) and one low affinity (microM) macroscopic dissociation constant for the binding of metal ions were found for the wild-type metallo-beta-lactamase from Bacillus cereus as well as six single-site mutants in which all ligands in the two metal binding sites were altered. Surprisingly, the mutations did not cause a specific alteration of the affinity of metal ions for the sole modified binding site as determined by extended x-ray absorption fine structure (EXAFS) and perturbed angular correlation of gamma-rays spectroscopy, respectively. Also UV-visible absorption spectra for the mono-cobalt enzymes clearly contain contributions from both metal sites. The observations of the very similar microscopic dissociation constants of both binding sites in contrast to the significantly differing macroscopic dissociation constants inevitably led to the conclusion that binding to the two metal sites exhibits negative cooperativity. The slow association rates for forming the binuclear enzyme determined by stopped-flow fluorescence measurements suggested that fast metal exchange between the two sites for the mononuclear enzyme hinders the binding of a second metal ion. EXAFS spectroscopy of the mono- and di-zinc wild type enzymes and two di-zinc mutants provide a definition of the metal ion environments, which is compared with the available x-ray crystallographic data.

Bacillus cereus↗

Eradication of intraperitoneal and distant tumor by adenovirus-mediated interferon-beta gene therapy is attributable to induction of systemic immunity.

Malignant mesothelioma remains an incurable disease for which immune-modulatory therapies, such as exogenous cytokines, have shown some promise. One such cytokine, IFN-beta, has potent antiproliferative and immunostimulatory activity in vitro, but its in vivo use has been limited by toxicity. We thus conducted studies evaluating intracavitary delivery of a replication-deficient adenoviral (Ad) vector encoding for the murine IFN-beta gene (Ad.muIFN-beta) in mouse models of malignant mesothelioma. In contrast to multiple injections of recombinant protein, a single i.p. injection of Ad.muIFN-beta into animals with established tumors elicited remarkable antitumor activity leading to long-term survival in >90% of animals bearing either AB12 or AC29 i.p. mesotheliomas. A control adenovirus vector had minimal antitumor effect in vivo. Significant therapeutic effects were also seen in animals treated with large tumor burdens. Importantly, treatment of i.p. tumor also led to reduction of growth in tumors established at a distant site (flank). A number of experiments suggested that these effects were attributable to an acquired CD8(+) T-cell-mediated response including: (a) the induction of long-lasting antitumor immunity; (b) loss of efficacy of Ad.muIFN-beta in tumor-bearing, immune-deficient (SCID, SCID/beige) mice; (c) detection of high levels of specific antitumor cytolytic activity from unstimulated splenocytes harvested from Ad.muIFN-beta-treated animals that was abolished by CD8(+) T-cell depletion; and (d) abrogation of antitumor effects of Ad.muIFN-beta in tumor-bearing CD8(+) T-cell-depleted animals. These data show that intracavitary IFN-beta gene therapy using an adenoviral vector provides strong CD8(+) T-cell-mediated antitumor effects in murine models of mesothelioma and suggest that this may be a promising strategy for the treatment of localized tumors such as mesothelioma or ovarian cancer in humans.

Adenoviridae↗