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Biomedical subjects

Arne Dietrich

Publications and source records attributed to Arne Dietrich.

11 recordsLinked to original sources

Transient hypofrontality as a mechanism for the psychological effects of exercise.

Although exercise is known to promote mental health, a satisfactory understanding of the mechanism underlying this phenomenon has not yet been achieved. A new mechanism is proposed that is based on established concepts in cognitive psychology and the neurosciences as well as recent empirical work on the functional neuroanatomy of higher mental processes. Building on the fundamental principle that processing in the brain is competitive and the fact that the brain has finite metabolic resources, the transient hypofrontality hypothesis suggests that during exercise the extensive neural activation required to run motor patterns, assimilate sensory inputs, and coordinate autonomic regulation results in a concomitant transient decrease of neural activity in brain structures, such as the prefrontal cortex, that are not pertinent to performing the exercise. An exercise-induced state of frontal hypofunction can provide a coherent account of the influences of exercise on emotion and cognition. The new hypothesis is proposed primarily on the strength of its heuristic value, as it suggests several new avenues of research.

Adaptation, Psychological↗

Intraoperative subcutaneous or intrasplenic vaccination with modified autologous tumor cells leads to enhanced survival in a mouse tumor model.

PURPOSE: We investigated the effect of intraoperative intrasplenic or subcutaneous vaccination with modified tumor cells on tumor progression in a mouse model. METHODS: Pre-established B16 melanomas on C57/Bl6 mice were surgically removed; mice were vaccinated intraoperatively with B16 cells transfected with an IL-12-encoding pRSC construct, the empty plasmid, or B16 frozen cells. Cells were given either intrasplenically or subcutaneously. Intrasplenic effects of vaccination were examined along with survival data. Mice without tumor recurrence underwent a second tumor implantation. RESULTS: Animals administered IL-12 pRSC cells showed significant alterations in the spleen, such as higher percentages of (activated) CD4+ and CD8+ T cells and tumor-specific CD4+ T cells among splenocytes. The tumor recurrence rate after resection ranged from 13 to 36%. Cases with recurrent tumors in particular benefited in all therapy groups, resulting in enhanced (tumor-free) survival, reduced tumor growth and lower metastasis rates. Following macroscopic complete tumor resection, the optimum outcome resulted from vaccination with IL-12 pRSC cells into the spleen and subcutaneously administered frozen cells. Survival times were enhanced in all therapy groups after tumor reimplantation, although results were not significant. CONCLUSIONS: Intraoperative whole-cell vaccination with autologous tumor cells yields promising data, and could be considered as a future option in adjuvant cancer therapy.

Animals↗

Particle-mediated cytokine gene therapy leads to antitumor and antimetastatic effects in mouse carcinoma models.

BACKGROUND: We investigated the effects of continuous cancer gene therapy including (antigen-presenting cell) (APC) engineering and local stimulation of the immune system. MATERIALS AND METHODS: Lewis lung carcinomas and B16 melanomas, intradermally established on C57/Bl6 mice, were shot using a gene gun every 4th day with a combination of plasmids. The first therapy group received plasmids coding the genes for interleukin (IL)-12 and IL-2. The second therapy group was treated with plasmids coding for B7.1 interferon-gamma (IFN-gamma)/IL-12 alternated by a plasmid coding IL-2. Control were mice without any therapy or treatment with the empty plasmid. RESULTS: Gene therapy led to reduced tumor sizes in the therapy groups of both models (significant for the Lewis lung carcinoma). We found an enhanced survival and reduced tumor growth rate in the therapy groups; however, the effects were not significant. IL- 12/IL-2 therapy was more effective, compared to B7.1/IFN-gamma/IL-12 and IL-2. Cytokine gene transfer let to a significantly lower metastasis rate in Lewis lung carcinoma. CONCLUSIONS: Continuous particle-mediated gene transfer is easy to handle and shows good results. Gene therapy combining the genes coding for IL-12 and IL-2 was superior to additional IFN-gamma/B7.1. APC engineering does not appear to be sufficient in these poorly antigenic tumors.

Animals↗

Video-assisted thoracoscopic surgery for pulmonary nodules after computed tomography-guided marking with a spiral wire.

PURPOSE: Peripheral pulmonary nodules are preferably removed by minimally invasive techniques, such as video-assisted thoracoscopic (VATS) surgery. These nodules should be marked preoperatively for better intraoperative detection and removal. DESCRIPTION: Twenty-two cases with a single pulmonary nodule requiring surgical removal for histologic examination were included in a prospective study. Guided by computed tomography, nodules were marked preoperatively using a laser marker system and fixed with a spiral wire. The marked nodules were removed by VATS surgery immediately after the marking. EVALUATION: The marking wire was placed in all 22 patients without any complications. The marked nodule was completely removed by VATS surgery in 19 patients. Conversion to thoracotomy was necessary in 3 patients, twice because of thoracoscopy-related problems and once because of a marking failure. The average times for the marking procedure and operation were 24 minutes and 32 minutes, respectively. CONCLUSIONS: This new method of computed tomography-guided nodule marking with a spiral wire and subsequent VATS surgery is very efficient in terms of localization and stable fixation of subpleural pulmonary nodules.

Adult↗

Endurance exercise selectively impairs prefrontal-dependent cognition.

Two experiments are reported that examine the possibility that exercise selectively influences different types of cognition. To our knowledge, these experiments represent the first attempt to study higher-cognitive processes during exercise. Theoretical thinking was guided by the transient hypofrontality hypothesis. In both experiments, athletes who exercised at a sustained, moderate pace were compared to sedentary controls on two neuropsychological tests, one that is generally regarded as heavily dependent on prefrontal cognition and one that is relatively insensitive to prefrontal operation. Results showed that during exercise performance on tests demanding prefrontal-dependent cognition was impaired, while at the same time, cognitive processes requiring little prefrontal activity were unaffected.

Adolescent↗

Neurocognitive mechanisms underlying the experience of flow.

Recent theoretical and empirical work in cognitive science and neuroscience is brought into contact with the concept of the flow experience. After a brief exposition of brain function, the explicit-implicit distinction is applied to the effortless information processing that is so characteristic of the flow state. The explicit system is associated with the higher cognitive functions of the frontal lobe and medial temporal lobe structures and has evolved to increase cognitive flexibility. In contrast, the implicit system is associated with the skill-based knowledge supported primarily by the basal ganglia and has the advantage of being more efficient. From the analysis of this flexibility/efficiency trade-off emerges a thesis that identifies the flow state as a period during which a highly practiced skill that is represented in the implicit system's knowledge base is implemented without interference from the explicit system. It is proposed that a necessary prerequisite to the experience of flow is a state of transient hypofrontality that enables the temporary suppression of the analytical and meta-conscious capacities of the explicit system. Examining sensory-motor integration skills that seem to typify flow such as athletic performance, writing, and free-jazz improvisation, the new framework clarifies how this concept relates to creativity and opens new avenues of research.

Attention↗

Combined percutaneous transhepatic biliary drainage with port implantation for management of patients with malignant biliary obstruction.

BACKGROUND: Endoscopic biliary stent insertion has become a standard palliative treatment for patients with obstructive jaundice caused by malignancies of the hepatobiliary system or metastases of other tumors, such as pancreatic or gastric cancer. Unfortunately, bacterial colonization and encrustation frequently leads to occlusion of plastic stents and, consequently, recurrent cholangitis. METHODS: An external-internal Yamakawa-type endoprosthesis was modified and combined with a titanium, subcutaneously implanted port. This technique was evaluated as a new approach to prolongation of stent patency and prevention of cholangitis. Two patients with obstructive jaundice, one with recurrent gastric carcinoma and the other with invasive gallbladder cancer, underwent treatment with this new method. RESULTS: Effective biliary drainage was established and cholangitis was prevented in both patients for 6 and 2 months, respectively. CONCLUSIONS: A new method of percutaneous transhepatic drainage combined with port implantation was effective and safe in two patients. This technique may be a reasonable treatment option for selected patients, but further evaluation in a larger series is required to establish efficacy and safety.

Aged↗

The cognitive neuroscience of creativity.

This article outlines a framework of creativity based on functional neuroanatomy. Recent advances in the field of cognitive neuroscience have identified distinct brain circuits that are involved in specific higher brain functions. To date, these findings have not been applied to research on creativity. It is proposed that there are four basic types of creative insights, each mediated by a distinctive neural circuit. By definition, creative insights occur in consciousness. Given the view that the working memory buffer of the prefrontal cortex holds the content of consciousness, each of the four distinctive neural loops terminates there. When creativity is the result of deliberate control, as opposed to spontaneous generation, the prefrontal cortex also instigates the creative process. Both processing modes, deliberate and spontaneous, can guide neural computation in structures that contribute emotional content and in structures that provide cognitive analysis, yielding the four basic types of creativity. Supportive evidence from psychological, cognitive, and neuroscientific studies is presented and integrated in this article. The new theoretical framework systematizes the interaction between knowledge and creative thinking, and how the nature of this relationship changes as a function of domain and age. Implications for the arts and sciences are briefly discussed.

Age Factors↗

Antitumoral and antimetastatic effects of continuous particle-mediated cytokine gene therapy.

We established a mice tumor model to investigate the effects of continuous cancer gene therapy, including antigen-presenting cell (APC) engineering and local stimulation of the immune system. B16 melanoma or Lewis lung carcinoma cells were injected intradermally on the back of C57/BL6 mice. The overlaying dermis or the tumor was shot with a gene gun (particle-mediated gene transfer) starting 8 days after tumor implantation in the case of the melanoma (Lewis lung carcinoma start day 7), continuing every fourth day thereafter until death. Control groups were mice without any therapy (A) or gene therapy with the empty plasmid (B). Therapy groups (Melanoma) received the genes as follows: group C--day 8, IL-12; day 12, IL-2...; group D--day 8, IFN-gamma/B7.1; day 12, IFN-gamma/B7.1...; group E--day 8, IFN-gamma/B7.1; day 12, IL-12, day 16, IL-2.... Melanoma: Mean survival time was enhanced in all therapy groups significantly, whereby the greatest survival time was found in group C. Tumor growth was reduced in all therapy groups similarly (C and D significant). Lewis Lung: Only mice of group C had an enhanced survival and reduced tumor growth (both significant). An antimetastatic effect was seen in all therapy groups.

Animals↗

Functional neuroanatomy of altered states of consciousness: the transient hypofrontality hypothesis.

It is the central hypothesis of this paper that the mental states commonly referred to as altered states of consciousness are principally due to transient prefrontal cortex deregulation. Supportive evidence from psychological and neuroscientific studies of dreaming, endurance running, meditation, daydreaming, hypnosis, and various drug-induced states is presented and integrated. It is proposed that transient hypofrontality is the unifying feature of all altered states and that the phenomenological uniqueness of each state is the result of the differential viability of various frontal circuits. Using an evolutionary approach, consciousness is conceptualized as hierarchically ordered cognitive function. Higher-order structures perform increasingly integrative functions and thus contribute more sophisticated content. Although this implies a holistic approach to consciousness, such a functional hierarchy localizes the most sophisticated layers of consciousness in the zenithal higher-order structure: the prefrontal cortex. The hallmark of altered states of consciousness is the subtle modification of behavioral and cognitive functions that are typically ascribed to the prefrontal cortex. The theoretical framework presented yields a number of testable hypotheses.

Consciousness↗

Complex cancer gene therapy in mice melanoma.

OBJECTIVE: We investigated the effects of continuous cancer gene therapy, including APC engineering and local stimulation of the immune system in a mice melanoma model. MATERIALS AND METHODS: B16 melanoma cells were injected into C57/Bl6 mice intradermally. The overlying dermis or the tumor were shot with different plasmids using a gene gun every 4th day starting 8 days after tumor implantation. Control groups were mice without any therapy or gene therapy as described above with the empty plasmid. Therapy was: group I, IL-12 and IL-2; group II, IFN-gamma/B7.1; group III, IFN-gamma/B7.1, IL-12, and IL-2. RESULTS: The median survival time of all therapy groups was significantly enhanced. The longest median survival was in the IL-12/IL-2 group. Tumor growth was reduced in all therapy groups. Control groups suffered a higher rate of metastasis and had fewer inflammatory cells at the tumor site. CONCLUSIONS: Continuous therapy with the gene gun is easy to handle and shows good results. Therapy with genes for IL-12 and IL-2 was superior to that with additional IFN-gamma/B7.1 or IFN-gamma/B7.1 alone. APC engineering is clearly less sufficient in the case of the B16 melanoma.

Animals↗