Analysis of surgical management of calvarial tumours and first results of a newly designed robotic trepanation system.

This study was performed to evaluate the surgical strategy in patients with calvarial tumours, in order to design and modify a robot-assisted trepanation system. A total of 75 patients underwent craniectomy for the treatment of calvarial tumours during the 10-year period from 1993 to 2002. The patients' complaints, the size, location and histology of the tumour, and the various cranioplasty techniques used were analysed retrospectively. In a second procedure several craniectomies at typical locations according to the study's results were performed in a laboratory setting using a hexapod robotic tool, constructed at the Helmholtz-Institute, RWTH Aachen University, and plastic model heads. The workflow was documented and the reproducibility and the accuracy of the procedure were registered. A total of 83 surgical procedures were performed on 75 patients. The majority (87 %) of lesions treated surgically were located in the frontal, temporal and anterior parts of the parietal region. Histological examination revealed benign lesions in 66 % of the patients and dural involvement in 46 %. According to these results craniectomies were performed using the robotic system. Mean positioning accuracy of the robotic system while milling was 0.24 mm, with a standard deviation of 0.04 mm, and maximum error under 1 mm. Craniectomies leaving a 1-mm layer of the tabula interna intact to ensure a healthy dura were performed in several regions successfully. The majority of calvarial tumours, requiring surgical treatment in our patients, were located in cosmetically relevant areas in which drilling can be carried out with the robotic trepanation system. Consequently, the surgical approach had to be planned carefully in order to achieve a good cosmetic outcome.     

Angiostatin overexpression in Morris hepatoma results in decreased tumor growth but increased perfusion and vascularization.

Growth of malignant tumors is dependent on sufficient blood supply. Thus, inhibition of tumor angiogenesis is emerging as a promising target in the treatment of malignancies. Human angiostatin (hANG) is one of the most potent inhibitors of endothelial cell proliferation, angiogenesis, and tumor growth in vivo. However, its mechanisms operating in vivo are not well understood. METHODS: To obtain more information about functional changes in the angiogenic process, we established Morris hepatoma (MH3924A) cell lines expressing hANG (hANG-MH3924A). The effects of hANG expression on proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) were measured in coculture experiments in vitro. To evaluate changes in tumor perfusion and blood volume, H2 15O and 68Ga-DOTA-albumin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid) were used for PET studies in vivo. Additionally, immunohistologic quantification of vascularization, apoptosis, and proliferation as well as gene array analyses were performed. RESULTS: Our in vitro experiments demonstrate reduced proliferation and increased apoptosis in HUVECs when being cocultured with hANG-MH3924A. In support, tumor growth of hANG-MH3924A is diminished by 95% in vivo. However, tumor perfusion and blood volume are increased in hANG-MH3924A corresponding to an increased microvessel density. Furthermore, hANG-transfected tumors show changes in expression of genes related to apoptosis, stress, signal transduction, and metabolism. CONCLUSION: hANG expression leads to inhibition of tumor growth, increased apoptosis, and changes in the expression of multiple genes involved in stress reactions, signal transduction, and apoptosis, which indicates a multifactorial reaction of tumors. An enhanced microvessel density is seen as part of these reactions and is associated with increased perfusion as measured by PET.     

Differential inhibition of cyclooxygenase-1 (COX-1) and-2 (COX-2) by NSAIDS: Consequences on anti-inflammatory activity versus gastric and renal safety

The discovery of an inducible isoform of cyclooxygenase (COX-2) requires a refinement of the theory that inhibition of cyclooxygenase activity is responsible for both therapeutic and side-effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Pharmacological results with developmental compounds suggest that COX-2 is the relevant target for the therapeutic (i.e. anti-inflammatory) effects of NSAIDs, whereas gastric and renal side-effects are related to inhibition of constitutive COX-1. However a role of COX-1 in inflammation cannot be excluded. Furthermore, more research effort is needed to investigate the functional relevance of COX-2 in normal tissue.     

The influence of caloric nystagmus on flash evoked transient and steady-state potentials.

OBJECTIVE: Caloric stimulation leads to a reduction of the cerebral blood flow in the visual cortex. This reduction has been attributed to the suppression of visual input caused by nystagmus induced by caloric stimulation. We investigated the influence of caloric stimulation on transient flash and steady-state flash visual evoked potentials. METHODS: Visual evoked potentials to 1 and 10 Hz flash stimulation were recorded in 12 normal subjects at baseline, during nystagmus induced by caloric stimulation with cold water, and after the cessation of nystagmus. RESULTS: Neither the amplitude of the transient flash visual evoked potentials (1 Hz stimulation) nor the amplitude of the steady-state flash visual evoked potentials (10 Hz stimulation) was influenced by caloric stimulation compared to baseline. CONCLUSIONS: The deactivation of the visual cortex by caloric stimulation does not seem to affect transient flash or steady-state flash visual evoked potentials. Reduction of cerebral blood flow in the visual cortex does not affect the processing of visual qualities (e.g., luminance and pattern). SIGNIFICANCE: Caloric stimulation does not reduce the amplitudes of transient flash or steady-state flash visual evoked potentials.     

Quantitative topographical analysis of effects of single thiopental bolus on human electroencephalogram.

The aim of present study was to characterize the topographical effect of thiopental on the EEG during induction of anesthesia. A multichannel (19 channels) digital EEG was recorded in 10 patients undergoing surgical treatment. The period during induction of anaesthesia before intubation was investigated in regard to peak frequency, amplitude, topography, and amplitude in conventional frequency bands. The main findings were a slowing of the EEG with a simultaneous increase of amplitude in the predominant EEG frequency (peak frequency) during induction. The topographical analysis showed a clear change of localization of the peak frequency in the occipito-frontal direction. Berger described the effect of thiopental on electrical cortical activity as early as 1933. Since then, many studies have investigated its influence on the EEG, but few have tried to characterize the effects of topographical changes in a quantitative way.     

Effect of cholesterol deprivation on piglet small intestine and serum lipids

Using the neonatal piglet, the effects of dietary cholesterol deprivation on growth, intestinal enzyme activity, intestinal and hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), and serum lipid were studied. Six litters of piglets were randomly assigned to one of two feeding regimens: restricted (800 ml of formula/24 h) versus unrestricted (1,200 ml of formula/24 h). Within litters, piglets were separated by sex, then randomly assigned to a formula containing low cholesterol (less than 2 mg/dl) or high cholesterol (145 mg/dl). Piglets were fed for 2 weeks. Male piglets in the restricted low cholesterol group gained significantly less weight per milliliter of formula than the restricted high cholesterol males. No effect was observed in the females. Microvillus membrane lactase activity was greater in males fed a high versus low cholesterol diet. Intestinal and hepatic HMG-CoA reductase activities and serum lipid profiles showed a trend toward compensation for dietary cholesterol deprivation but did not differ statistically between the cholesterol-fed versus -deprived groups. It is concluded that dietary cholesterol deprivation in the male neonatal pig causes alterations in growth, but no other statistically significant responses were detectable in this study.     

Passive electrical properties of motoneurons in aged cats following axotomy

The objective of this study was to determine whether the aging process influences the changes in the electrophysiological properties of motoneurons that occur as a consequence of axotomy. Accordingly, using intracellular recording and stimulating techniques, the basic electrical properties of control (unaxotomized) and axotomized spinal cord motoneurons of aged cats were determined. Compared with control motoneurons, axotomized motoneurons exhibited increases in input resistance (R_in), membrane time constant (τ_b) and the equalizing time constant (τ_c). While the electrotonic length (L) remained unchanged, axotomy induced a decrease in the total cell capacitance (C_cell. The post-axotomy reduction of C_cell indicates that the motoneuron surface area was reduced and the increased membrane time constant indicates that there was an increase in membrane resistivity (R_m). The post-axotomy conservation of L accompanied by an increase in R_m suggests that aged axotomized motoneurons undergo geometrical changes. Furthermore, calculations based on cable theory suggest that the diameter of the equivalent cylinder (d) decreased following axotomy, whereas the equivalent cylinder length (l) remained unaffected. It is concluded that axotomy produces significant alterations in the soma-dendritic portion of aged spinal motoneurons, as indicated by the changes found in their passive electrophysiological properties, and that the pattern of the response that occurs in axotomized motoneurons of adult cats is also present in axotomized motoneurons of aged animals.     

Reversal of gelatin-impaired wound healing in rats by exogenous fibronectin.

Animal experiments have shown that administration of gelatin results in a deprivation of plasma fibronectin (FN) and impaired wound healing. For further elucidation of these findings a therapy study with purified human FN was performed in rats. Fifty animals received a standard burn injury of 1% body surface and were divided into five experimental groups. Positive controls given no further treatment or treated with solvent only served for estimation of normal healing. For a negative control, 10 animals received three intraperitoneal injections of gelatin (58 mg/kg body wt) on Days 0, 1, and 2 after injury. They exhibited a striking lack of plasma FN (Day 1) and a significant delay of wound contraction (Days 7 and 14). In the therapy groups each administration of gelatin was followed by an intraperitoneal or intracardiac injection of FN (58 mg/kg body wt) 1 hr later. In these animals the negative effect of gelatin upon plasma FN and wound contraction was prevented. According to this study wound healing is menaced by FN deficiency and can be optimized by substitution of exogenous FN.