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Biomedical subjects

E W Lang

Publications and source records attributed to E W Lang.

33 records · Page 2Linked to original sources
PubMed1998

Simulations on the selectivity of 5-aminolaevulinic acid-induced fluorescence in vivo.

The knowledge of the exact time course of a photosensitizer in tumour and surrounding host tissue is fundamental for effective photodynamic therapy (PDT) and fluorescence-based diagnosis. In this study the time course of porphyrin fluorescence following topical application of 5-aminolaevulinic acid (ALA) using different formulations, concentrations and incubation times has been measured in amelanotic melanomas (A-Mel-3) (n = 54) grown in transparent dorsal skinfold chambers of Syrian golden hamsters and in human basal cell carcinomas (BCCs) (n = 40) in vivo. To simulate the accumulation of ALA-induced protoporphyrin IX (Pp IX), a three-compartment model has been developed and rate constants have been determined. The kinetics of both the A-Mel-3 tumours and the BCCs show a significantly higher fluorescence intensity in tumour as compared to normal surrounding host tissue. Maximal fluorescence intensity in A-Mel-3 tumours as a percentage of the reference standard used occurs 150 min post incubation (p.i.) using a 1, 3 or 10% (vol.) ALA solution buffered to pH 7.4 and 1 h incubation time. After a 4 h incubation time maximal fluorescence intensity in tumour is measured shortly p.i. A concentration of 10% ALA does not increase the fluorescence intensity as compared to 3% ALA following 4 h incubation, but either 3 or 10% ALA yields a significantly higher fluorescence after 4 h incubation time as compared to 1 h. The fluorescence intensity following an 8 h incubation reaches its maximum directly p.i. for all concentrations and then decreases exponentially. The fluorescence intensity in the surrounding host tissue shows no statistically significant difference regarding concentration or incubation time. At least during the first hour p.i., the fluorescence intensity measured in the surrounding tissue is lower as compared to that in the tumour in all groups. 24 h after topical application hardly any fluorescence is detectable in tumour or surrounding host tissue in all experimental groups. Incubating human BCCs with a 20% ALA cream (water-in-oil emulsion) or a 20% ALA gel (containing 40% dimethyl sulfoxide) for approximately 2 h yields a similar fluorescence intensity directly after incubation for either cream or gel. However, while yielding a maximum 120 min p.i. with cream, the fluorescence intensity increases for a longer time (about 2-3 h p.i.) and up to higher values using the gel formulation. In surrounding normal skin, cream as well as gel formulation yields a similar fluorescence intensity directly after incubation. Afterwards the fluorescence intensity decreases slowly using the cream whereas a further increase of the fluorescence intensity is measured in the normal skin with a maximum 240 min p.i. using the gel formulation. The results of the proposed three-compartment model indicate that the observed selectivity of accumulated porphyrins following topical application of ALA is mainly governed by an increased ALA penetration of the stratum corneum of the skin, an accelerated ALA uptake into the cell and a higher porphyrin formation in tumour as compared to normal skin tissue, but not by a reduced ferrocheletase activity.

Aminolevulinic Acid↗
PubMed1998

The utility of contrast-enhanced MR-angiography for posterior fossa giant cerebral aneurysm management.

The utility of magnetic resonance angiography is sometimes limited in the diagnostic workup of cerebral aneurysms with low flow and/or partial thrombosis when weighed against digital subtraction angiography. We present the case of a rare superior cerebellar artery giant, partially thrombosed aneurysm in which additional i.v. contrast-enhanced MRA sequences were comparable to digital subtraction angiography. It demonstrated not only the exact spatial resolution and correct anatomical relation but also the hemodynamics which were confirmed by intraoperative Doppler ultrasound. This report supports the feasibility and utility of i.v. contrast-enhanced MRA for posterior fossa giant cerebral aneurysm management.

Cerebellum↗
PubMed1997

Outcome after severe head injury: an analysis of prediction based upon comparison of neural network versus logistic regression analysis.

More reliable prediction of outcome would be helpful for clinicians who treat severely head-injured patients. To determine if neural network modeling would improve outcome prediction compared with standard logistic regression analysis and to determine if data available 24 h after severe head injury allows better prediction than data obtained within 6 h, we tested the ability of both techniques at these two times to predict outcome (dead versus alive) at 6 months. One thousand sixty-six consecutive patients with Glasgow Coma Scale scores of 8 or less during the first 24 h after injury were randomly divided into two groups. Data from the first group (n = 799) were used to develop the models; data from the second group (n = 267) were used to test the accuracy, sensitivity, and specificity of the models by comparing predicted and actual outcomes. The 6-month mortality rate was 63.5%. Our findings confirm the importance of age, Glasgow Coma Scale scores, and hypotension in predicting outcome. Using data available at 24 h improved the predictive power of both models compared with admission data; at both time points, however, the differences in the results obtained with the two models were negligible. We conclude that outcome (dead versus alive) at 6 months after severe head injury can be predicted with logistic regression or neural network models based on data available at 24 h. Critical therapeutic decisions, such as cessation of therapy, should be based on the patient's status 1 day after injury and only rarely on admission status alone.

Adolescent↗
PubMed1996

Myogenic motor-evoked potential monitoring using partial neuromuscular blockade in surgery of the spine.

STUDY DESIGN: The authors analyzed motor-evoked potentials using transcranial electrical cortical stimulation during spinal surgery in 40 patients under conditions of partial neuromuscular blockade. OBJECTIVES: The results were used to investigate the utility of motor-evoked potential monitoring to prevent neurologic injury in spinal surgery. SUMMARY OF BACKGROUND DATA: Noninvasive transcranial electrical motor-evoked potentials are reportedly effective in predicting postoperative spinal cord deficits caused by intraoperative occurrences. However, the sensitivity and specificity of these predictions have not been assessed under conditions of partial neuromuscular blockade during a wide variety of surgical procedures. METHODS: Compound muscle action potentials were recorded at the tibialis anterior muscle while general anesthesia was maintained with nitrous oxide, etomidate, and sufentanil. Surgery was performed at all spinal levels for a variety of diagnoses. RESULTS: Reference motor-evoked potential amplitudes, measured after induction of partial neuromuscular blockade, ranged from 25 to 7562 microV (median, 600 microV). Variation in intraoperative motor-evoked potential amplitude ranged from signal loss to a 3440% increase. A decrease to less than 20% of the individual reference value for motor-evoked potential amplitude occurred at least once in nine patients (22.5%) but as not associated with postoperative motor deficits. Two patients who had loss of motor-evoked potential signal without recovery did have postoperative motor deficits. Motor-evoked potentials predicted postoperative motor improvement in six patients. An improvement threshold of 160% of the reference amplitude predicted postoperative motor improvement with 100% sensitivity and 81% specificity. CONCLUSIONS: The authors support the utility of recording transcranial electrical motor-evoked potentials in spinal surgery under partial neuromuscular blockade. Recovery of lost motor-evoked potentials was not associated with postoperative motor deficits, whereas non-recovery of lost motor-evoked potentials was.

Adolescent↗
PubMed1996

Intervertebral disc space infection caused by Aspergillus fumigatus.

The authors describe the case of a 53-year-old woman who suffered from an Aspergillus fumigatus infection of the L2/3 intervertebral disc space unrelated to previous operations on her lumbar spine. After surgical debridement combined with amphotericin therapy she died on the 23rd postoperative day from a fulminant bacterial sepsis of pulmonary origin. Although she had intermittently used steroids for bronchial asthma, this is an unusual case of fungal infection of the lumbar spine in an apparently immunocompetent patient.

Amphotericin B↗
PubMed1996

Urinary retention and space-occupying lesions of the frontal cortex.

The authors present 2 cases in which urinary retention was related to supratentorial cortical lesions. These cases support the presence and function of a supratentorial center involved in control of the voiding reflex loop and indicate that lesions affecting this center can result in urinary retention rather than the syndrome of incontinence, urgency, and increased urinary frequency that is generally attributed to dysfunction of this system. In such cases, a clinical presentation of urinary retention in the absence of associated remarkable neurological deficits renders clinical evidence as a localizing sign.

Aged↗
PubMed1995

Variability of vascular territory in stroke. Pitfalls and failure of stroke pattern interpretation.

BACKGROUND AND PURPOSE: We investigated the efficacy and feasibility of determining infarction mechanisms and underlying embolic or hemodynamic pathologies from topographical patterns of ischemic damage seen on computed tomography or magnetic resonance imaging. METHODS: Infarction patterns from 22 patients with ipsilateral severe, hemodynamically relevant carotid stenosis (n = 6) or occlusions (n = 16) were superimposed, using two matching algorithms, onto maps showing the variability of the cerebral vascular territories as determined from recent cadaver studies. These images were used to classify the infarctions as border-zone or territorial for the two conditions of minimal and maximal middle cerebral artery distribution. RESULTS: Classification of infarction patterns resulting from carotid stenosis was independent of the territorial extension map chosen: 83% were classified as territorial. Classification of patterns due to carotid occlusion, however, varied highly; 81% of infarctions were considered territorial when the maximal middle cerebral artery distribution map was used, whereas only 19% were when the minimal territorial extension map was used. CONCLUSIONS: The current concept that stroke mechanisms can be inferred from the interpretation of stroke patterns seen on computed tomography scans or magnetic resonance imaging is significantly confounded by the demonstrated variability in intracranial vascular distributions. Stroke pattern interpretation appears to be highly dependent on the in vivo vascular tree of the individual, which is unknown to the examiner. This calls into question the reliability of classifying infarction patterns as border-zone or territorial. Determination of true underlying stroke mechanisms requires a comprehensive approach and cannot be based solely on stroke pattern interpretation.

Brain↗
PubMed1995

Intracranial pressure and cerebral perfusion pressure in severe head injury.

Monitoring and management of intracranial pressure (ICP) are fundamental to modern neurotraumatology. Although never formally proven to independently improve outcome in prospective, randomized, placebo-controlled trials, there is such a predominance of indirect support for this modality that most neurotrauma protocols are impossible with-out its inclusion and ethical considerations virtually preclude placebo-controlled trials of its efficacy. In addition to the question of improving outcome, ICP monitoring is also useful in guiding the use of potentially harmful treatment modalities such as hyperventilation, mannitol, and barbiturates, and also provides important prognostic data. ICP monitoring provides information on the likelihood of cerebral herniation and allows calculation of the cerebral perfusion pressure (CPP). Although there is no constant threshold for herniation, the most commonly used treatment threshold is 20 to 25 mm Hg. In addition, ICP trends are indispensable in providing the earliest possible indication of critical intracranial mass effects when combined with other clinical indicators. CPP is the difference between mean arterial pressure and ICP. CPP is an important clinical indicator of cerebral blood flow (CBF). Cerebral autoregulation generally remains at least partially preserved after severe head injury, although the CPP value at which it is activated appears to be shifted upward. Therefore, maintaining adequate CBF appears to require using an elevated minimal CPP threshold when treating the injured brain. A generally accepted value of 70 mm Hg is suggested.

Brain Ischemia↗
PubMed1994

Intracranial pressure. Monitoring and management.

Monitoring of ICP from the subarachnoid, intraparenchymal, or ventricular spaces can be accomplished easily and reliably. The risks and benefits of each approach should be considered when choosing the monitoring technique. The goal of ICP management is to prevent herniation and to optimize cerebral perfusion. Even transient episodes of post-traumatic cerebral ischemia due to inadequate CPP can quickly nullify all resuscitative efforts. The provision of sufficient CBF is complicated by the varying degree of disruption of pressure autoregulation commonly resulting from head trauma. Post-injury, there is a need to provide a CPP which is elevated to some extent with respect to that sufficient in uninjured brains. This generally requires a CPP of at least 70 mm Hg, which must be accomplished by maintaining an adequate MAP while controlling ICH. Although ICH can generally be controlled using methods commonly employed, the majority of these techniques have potential complications. Additionally, there is increasing evidence that significant variation exists in the pathologic processes driving ICH in individual patients. Therefore, goals such as the desired CPP and conditions such as the relative contribution of edema, cerebral hypervolemia, and ischemia to ICH should optimally be considered in a patient-specific fashion and allow a targeted approach to therapy.

Barbiturates↗
PubMed1993

Emergence of orientation selective simple cells simulated in deterministic and stochastic neural networks.

The processing of visual data in area 17 of the mammalian cortex is mainly performed by cells with receptive fields which are tuned to different orientations of input stimuli. The mechanisms underlying the emergence of receptive field properties of orientation selective cells are not well understood up to now. Recently, some models for the prenatal development of the receptive fields of orientation selective simple cells have been proposed, which emerge in neural networks trained by Hebb type unsupervised learning rules. These models, however, use different network architectures and are restricted to the case of identical input neurons. In this work, a biologically motivated neural network model with a general architecture is presented. It is trained with a Hebb type updating rule and with uncorrelated input. The input neurons are identified with retinal ganglion cells and exhibit mature Mexican hat type receptive fields. If the receptive fields of the input neurons have identical properties (deterministic model), a set of parameter domains is found, which characterize different kinds of receptive field maturation behaviour of the network. Results obtained by other authors with similar models are contained in this description as special cases. In addition, the more general and rarely investigated stochastic model, where random variations of the parameters describing the receptive fields of the input neurons occur, is investigated. A high sensitivity of the network against these random variations is obtained. In case of large variations of receptive field parameters of the ganglion cells, a qualitatively new kind of maturation behaviour appears. A significant part of the synaptic connections from ganglion cells to the cortical cell is removed and small simple cell receptive fields with only few lobes emerge. The stochastic model is found to provide a better description of the size, scatter and structure of receptive fields present in biological systems, than the deterministic model.

Animals↗
PubMed1986

Physical-chemical limits for the stability of biomolecules.

Water is an indispensable prerequisite for the existence of life. Only in an aqueous environment can biomolecules take up their native, tertiary structure and organize themselves into higher aggregates like multienzyme complexes or cell-organelles. In most of these processes interactions between biomolecules and water play an important role. The influence of pressure and temperature upon intramolecular interactions of biopolymers and biopolymer-water interactions are discussed. Because of fast hydrolysis biomolecules should be unstable at T > or = 500 K. Hydrostatic pressure leads to an accelerated hydrolysis. The p,T-dependence of hydrophobic interactions suggest an even lower upper boundary around T approximately 400 K. In the model system t-butanol/water compression weakens hydrophobic interactions. However, within the modest pressure range p < or = 120 MPa observed on earth hydrostatic pressure does not seem to limit the stability of biomolecules at temperatures below 400 K severely.

Biophysical Phenomena↗
PubMedDate not supplied

A neural network model for the self-organization of cortical grating cells.

A neural network model with incremental Hebbian learning of afferent and lateral synaptic couplings is proposed,which simulates the activity-dependent self-organization of grating cells in upper layers of striate cortex. These cells, found in areas V1 and V2 of the visual cortex of monkeys, respond vigorously and exclusively to bar gratings of a preferred orientation and periodicity. Response behavior to varying contrast and to an increasing number of bars in the grating show threshold and saturation effects. Their location with respect to the underlying orientation map and their nonlinear response behavior are investigated. The number of emerging grating cells is controlled in the model by the range and strength of the lateral coupling structure.

Animals↗
PubMedDate not supplied

Self-organization of local cortical circuits and cortical orientation maps: a nonlinear Hebbian model of the visual cortex with adaptive lateral couplings.

A nonlinear, recurrent neural network model of the visual cortex is presented. Orientation maps emerge from adaptable afferent as well as plastic local intracortical circuits driven by random input stimuli. Lateral coupling structures self-organize into DOG profiles under the influence of pronounced emerging cortical activity blobs. The model's simplified architecture and features are modeled to largely mimik neurobiological findings.

Animals↗
PubMedDate not supplied

An incremental Hebbian learning model of the primary visual cortex with lateral plasticity and real input patterns.

We present a simplified binocular neural network model of the primary visual cortex with separate ON/OFF-pathways and modifiable afferent as well as intracortical synaptic couplings. Random as well as natural image stimuli drive the weight adaptation which follows Hebbian learning rules stabilized with constant norm and constant sum constraints. The simulations consider the development of orientation and ocular dominance maps under different conditions concerning stimulus patterns and lateral couplings. With random input patterns realistic orientation maps with +/- 1/2-vortices mostly develop and plastic lateral couplings self-organize into mexican hat type structures on average. Using natural greyscale images as input patterns, realistic orientation maps develop as well and the lateral coupling profiles of the cortical neurons represent the two point correlations of the input image used.

Algorithms↗