bluuebunny/crossref_metadata_2025 huggingface dataset:
Mediators and Mechanisms of Change in Psychotherapy Research
Authors: Kazdin Alan E.
Published: March 2007

There has been enormous progress in psychotherapy research. This has culminated in recognition of several treatments that have strong evidence in their behalf. Even so, after decades of psychotherapy research, we cannot provide an evidence-based explanation for how or why even our most well studied interventions produce change, that is, the mechanism(s) through which treatments operate. This chapter presents central requirements for demonstrating mediators and mechanisms of change and reviews current data-analytic and designs approaches and why they fall short of meeting these requirements. The role of the therapeutic alliance in psychotherapy and cognitive changes in cognitive therapy for depression are highlighted to illustrate key issues. Promising lines of work to identify mediators and mechanisms, ways of bringing to bear multiple types of evidence, recommendations to make progress in understanding how therapy works, and conceptual and research challenges in evaluating mediators and mechanisms are also presented.
Relapse and Relapse Prevention
Authors: Brandon Thomas H. , Vidrine Jennifer Irvin , Litvin Erika B.
Published: March 2007

Most psychological disorders and problem behaviors are characterized by very high rates of postremittance relapse. Thus, advances in the long-term efficacy of psychological interventions require understanding the causes and processes of relapse, with the ultimate goal of developing strategies that reduce the probability of relapse. Existing psychological theory and interventions relevant to relapse and relapse prevention (RP) are reviewed, with a focus on addictive behaviors. The past two decades have produced increased attention toward the relapse problem and important advances in the conceptualization of relapse (i.e., as a process rather than a discrete event). Further progress will require the translation of basic theory into applied theory, the development of integrative theories of relapse, and the design and testing of theory-based, multimodal RP interventions.
Coping Resources, Coping Processes, and Mental Health
Authors: Taylor Shelley E. , Stanton Annette L.
Published: March 2007

Coping, defined as action-oriented and intrapsychic efforts to manage the demands created by stressful events, is coming to be recognized both for its significant impact on stress-related mental and physical health outcomes and for its intervention potential. We review coping resources that aid in this process, including individual differences in optimism, mastery, self-esteem, and social support, and examine appraisal and coping processes, especially those marked by approach or avoidance. We address the origins of coping resources and processes in genes, early life experience, and gene-environment interactions, and address neural underpinnings of coping that may shed light on evaluating coping interventions. We conclude by outlining possible intervention strategies for improving coping processes.
Dynamic Aspects of CNS Synapse Formation
Authors: McAllister A. Kimberley
Published: March 2007

The mammalian central nervous system (CNS) requires the proper formation of exquisitely precise circuits to function correctly. These neuronal circuits are assembled during development by the formation of synaptic connections between thousands of differentiating neurons. Proper synapse formation during childhood provides the substrate for cognition, whereas improper formation or function of these synapses leads to neurodevelopmental disorders, including mental retardation and autism. Recent work has begun to identify some of the early cellular events in synapse formation as well as the molecular signals that initiate this process. However, despite the wealth of information published on this topic in the past few years, some of the most fundamental questions about how, whether, and where glutamatergic synapses form in the mammalian CNS remain unanswered. This review focuses on the dynamic aspects of the early cellular and molecular events in the initial assembly of glutamatergic synapses in the mammalian CNS.
Copper and Iron Disorders of the Brain
Authors: Madsen Erik , Gitlin Jonathan D.
Published: March 2007

Copper and iron are transition elements essential for life. These metals are required to maintain the brain's biochemistry such that deficiency or excess of either copper or iron results in central nervous system disease. This review focuses on the inherited disorders in humans that directly affect copper or iron homeostasis in the brain. Elucidation of the molecular genetic basis of these rare disorders has provided insight into the mechanisms of copper and iron acquisition, trafficking, storage, and excretion in the brain. This knowledge permits a greater understanding of copper and iron roles in neurobiology and neurologic disease and may allow for the development of therapeutic approaches where aberrant metal homeostasis is implicated in disease pathogenesis.
Information Processing in the Primate Retina: Circuitry and Coding
Authors: Field G.D. , Chichilnisky E.J.
Published: March 2007

The function of any neural circuit is governed by connectivity of neurons in the circuit and the computations performed by the neurons. Recent research on retinal function has substantially advanced understanding in both areas. First, visual information is transmitted to the brain by at least 17 distinct retinal ganglion cell types defined by characteristic morphology, light response properties, and central projections. These findings provide a much more accurate view of the parallel visual pathways emanating from the retina than do previous models, and they highlight the importance of identifying distinct cell types and their connectivity in other neural circuits. Second, encoding of visual information involves significant temporal structure and interactions in the spike trains of retinal neurons. The functional importance of this structure is revealed by computational analysis of encoding and decoding, an approach that may be applicable to understanding the function of other neural circuits.
Molecular Architecture of Smell and Taste inDrosophila
Authors: Vosshall Leslie B. , Stocker Reinhard F.
Published: March 2007

The chemical senses—smell and taste—allow animals to evaluate and distinguish valuable food resources from dangerous substances in the environment. The central mechanisms by which the brain recognizes and discriminates attractive and repulsive odorants and tastants, and makes behavioral decisions accordingly, are not well understood in any organism. Recent molecular and neuroanatomical advances in Drosophila have produced a nearly complete picture of the peripheral neuroanatomy and function of smell and taste in this insect. Neurophysiological experiments have begun to provide insight into the mechanisms by which these animals process chemosensory cues. Given the considerable anatomical and functional homology in smell and taste pathways in all higher animals, experimental approaches in Drosophila will likely provide broad insights into the problem of sensory coding. Here we provide a critical review of the recent literature in this field and comment on likely future directions.
Neurobiology of Feeding and Energy Expenditure
Authors: Gao Qian , Horvath Tamas L.
Published: March 2007

Significant advancements have been made in the past century regarding the neuronal control of feeding behavior and energy expenditure. The effects and mechanisms of action of various peripheral metabolic signals on the brain have become clearer. Molecular and genetic tools for visualizing and manipulating individual components of brain homeostatic systems in combination with neuroanatomical, electrophysiological, behavioral, and pharmacological techniques have begun to elucidate the molecular and neuronal mechanisms of complex feeding behavior and energy expenditure. This review highlights some of these advancements that have led to the current understanding of the brain's involvement in the acute and chronic regulation of energy homeostasis.
Orbitofrontal Cortex and Its Contribution to Decision-Making
Authors: Wallis Jonathan D.
Published: March 2007

Damage to orbitofrontal cortex (OFC) produces an unusual pattern of deficits. Patients have intact cognitive abilities but are impaired in making everyday decisions. Here we review anatomical, neuropsychological, and neurophysiological evidence to determine the neuronal mechanisms that might underlie these impairments. We suggest that OFC plays a key role in processing reward: It integrates multiple sources of information regarding the reward outcome to derive a value signal. In effect, OFC calculates how rewarding a reward is. This value signal can then be held in working memory where it can be used by lateral prefrontal cortex to plan and organize behavior toward obtaining the outcome, and by medial prefrontal cortex to evaluate the overall action in terms of its success and the effort that was required. Thus, acting together, these prefrontal areas can ensure that our behavior is most efficiently directed towards satisfying our needs.
Peripheral Regeneration
Authors: Chen Zu-Lin , Yu Wei-Ming , Strickland Sidney
Published: March 2007

Whereas the central nervous system (CNS) usually cannot regenerate, peripheral nerves regenerate spontaneously after injury because of a permissive environment and activation of the intrinsic growth capacity of neurons. Functional regeneration requires axon regrowth and remyelination of the regenerated axons by Schwann cells. Multiple factors including neurotrophic factors, extracellular matrix (ECM) proteins, and hormones participate in Schwann cell dedifferentiation, proliferation, and remyelination. We describe the current understanding of peripheral axon regeneration and focus on the molecules and potential mechanisms involved in remyelination.
Dysregulation of intestinal crypt cell proliferation and villus cell migration in mice lacking Krüppel-like factor 9
Authors: Simmen Frank A. , Xiao Rijin , Velarde Michael C. , Nicholson Rachel D. , Bowman Margaret T. , Fujii-Kuriyama Yoshiaki , Oh S. Paul , Simmen Rosalia C. M.
Published: March 2007

Krüppel-like factor 9 (Klf9), a zinc-finger transcription factor, is implicated in the control of cell proliferation, cell differentiation, and cell fate. Using Klf9-null mutant mice, we have investigated the involvement of Klf9 in intestine crypt-villus cell renewal and lineage determination. We report the predominant expression of Klf9 gene in small and large intestine smooth muscle (muscularis externa). Jejunums null for Klf9 have shorter villi, reduced crypt stem/transit cell proliferation, and altered lineage determination as indicated by decreased and increased numbers of goblet and Paneth cells, respectively. A stimulatory role for Klf9 in villus cell migration was demonstrated by bromodeoxyuridine labeling. Results suggest that Klf9 controls the elaboration, from intestine smooth muscle, of molecular mediator(s) of crypt cell proliferation and lineage determination and of villus cell migration.
Sp1 and Sp3 mediate NHE2 gene transcription in the intestinal epithelial cells
Authors: Hua Ping , Xu Hua , Uno Jennifer K. , Lipko Maciej A. , Dong Jiali , Kiela Pawel R. , Ghishan Fayez K.
Published: March 2007

Our previous studies have identified a minimal Sp1-driven promoter region (nt −36/+116) directing NHE2 expression in mouse renal epithelial cells. However, this minimal promoter region was not sufficient to support active transcription of NHE2 gene in the intestinal epithelial cells, suggesting the need for additional upstream regulatory elements. In the present study, we used nontransformed rat intestinal epithelial (RIE) cells as a model to identify the minimal promoter region and transcription factors necessary for the basal transcription of rat NHE2 gene in the intestinal epithelial cells. We identified a region within the rat NHE2 gene promoter located within nt −67/−43 upstream of transcription initiation site as indispensable for the promoter function in intestinal epithelial cells. Mutations at nt −56/−51 not only abolished the DNA-protein interaction in this region, but also completely abolished NHE2 gene promoter activity in RIE cells. Supershift assays revealed that Sp1 and Sp3 interact with this promoter region, but, contrary to the minimal promoter indispensable for renal expression of NHE2, both transcription factors expressed individually in Drosophila SL2 cells activated rat NHE2 gene promoter. Moreover, Sp1 was a weaker transactivator and when coexpressed in SL2 cells it reduced Sp3-mediated NHE2 basal promoter activity. Furthermore, DNase I footprinting confirmed that nt −58/−51 is protected by nuclear protein from RIE cells. We conclude that the mechanism of basal control of rat NHE2 gene promoter activity is different in the renal and intestinal epithelium, with Sp3 being the major transcriptional activator of NHE2 gene transcription in the intestinal epithelial cells.
Cardiac atrophy in women following bed rest
Authors: Dorfman Todd A. , Levine Benjamin D. , Tillery Tommy , Peshock Ronald M. , Hastings Jeff L. , Schneider Suzanne M. , Macias Brandon R. , Biolo Gianni , Hargens Alan R.
Published: March 2007

Both chronic microgravity exposure and long-duration bed rest induce cardiac atrophy, which leads to reduced standing stroke volume and orthostatic intolerance. However, despite the fact that women appear to be more susceptible to postspaceflight presyncope and orthostatic hypotension than male astronauts, most previous high-resolution studies of cardiac morphology following microgravity have been performed only in men. Because female athletes have less physiological hypertrophy than male athletes, we reasoned that they also might have altered physiological cardiac atrophy after bed rest. Magnetic resonance imaging was performed in 24 healthy young women (32.1 ± 4 yr) to measure left ventricular (LV) and right ventricular (RV) mass, volumes, and morphology accurately before and after 60 days of 6° head-down tilt (HDT) bed rest. Subjects were matched and then randomly assigned to sedentary bed rest (controls, n = 8) or two treatment groups consisting of 1) exercise training using supine treadmill running within lower body negative pressure plus resistive training ( n = 8), or 2) protein (0.45 g·kg−1·day−1increase) plus branched-chain amino acid (BCAA) (7.2 g/day) supplementation ( n = 8). After sedentary bed rest without nutritional supplementation, there were significant reductions in LV (96 ± 26 to 77 ± 25 ml; P = 0.03) and RV volumes (104 ± 33 to 86 ± 25 ml; P = 0.02), LV (2.2 ± 0.2 to 2.0 ± 0.2 g/kg; P = 0.003) and RV masses (0.8 ± 0.1 to 0.6 ± 0.1 g/kg; P < 0.001), and the length of the major axis of the LV (90 ± 6 to 84 ± 7 mm. P < 0.001), similar to what has been observed previously in men (8.0%; Perhonen MA, Franco F, Lane LD, Buckey JC, Blomqvist Zerwekh JE, Peshock RM, Weatherall PT, Levine BD. J Appl Physiol 91: 645–653, 2001). In contrast, there were no significant reductions in LV or RV volumes in the exercise-trained group, and the length of the major axis was preserved. Moreover, there were significant increases in LV (1.9 ± 0.4 to 2.3 ± 0.3 g/kg; P < 0.001) and RV masses (0.7 ± 0.1 to 0.8 ± 0.2 g/kg; P = 0.002), as well as mean wall thickness (9 ± 2 to 11 ± 1 mm; P = 0.02). The interaction between sedentary and exercise LV and RV masses was highly significant ( P < 0.0001). Protein and BCAA supplementation led to an intermediate phenotype with no change in LV or RV mass after bed rest, but there remained a significant reduction in LV volume (103 ± 14 to 80 ± 16 ml; P = 0.02) and major-axis length (91 ± 5 to 88 ± 7 mm; P = 0.003). All subjects lost an equivalent amount of body mass (3.4 ± 0.2 kg control; 3.1 ± 0.04 kg exercise; 2.8 ± 0.1 kg protein). Cardiac atrophy occurs in women similar to men following sedentary 60 days HDT bed rest. However, exercise training and, to a lesser extent, protein supplementation may be potential countermeasures to the cardiac atrophy associated with chronic unloading conditions such as in spaceflight and prolonged bed rest.
Simulation of the apparent diffusion of helium-3 in the human acinus
Authors: Verbanck Sylvia , Paiva Manuel
Published: March 2007

Functional MRI of the lungs with hyperpolarized helium provides an index of apparent diffusion measured over several seconds (ADCsec) that is only 2% of its free diffusion in air (0.88 cm2/s). The potential of ADCsec to noninvasively assess in vivo lung structure of diseased lungs at the length scales corresponding to several seconds is critically dependent on the exact link between ADCsec and lung peripheral structure. To understand the intruigingly small ADCsec, numerical simulations of gas transport were performed in 1) a trumpet model, 2) a symmetrical, and 3) an asymmetrical multiple-branch-point model of the human acinus. For initial gas boluses in different locations of the acinar models, ADCsec was quantified as follows. At different time intervals, we computed a coefficient of variation (CoV) of the concentration distributions within each acinar model. The slope in the semilog plot of log(CoV) vs. time was proportional to the ADCsec generated by the internal model structure, provided that the outer model boundaries were similar across all models (i.e., similar cumulative cross section vs. average path length). The simulations revealed an ADCsec that amounted to ∼1% of free diffusion in the trumpet model of the acinus, i.e., corresponding to free diffusion within the acinar geometric boundaries. Our simulations show that for initial conditions corresponding to those used in MRI experiments, intra-acinar branching introduces a dramatic diffusion delay, comparable to what is observed experimentally.
Alterations in autonomic function and cerebral hemodynamics to orthostatic challenge following a mountain marathon
Authors: Murrell Carissa , Wilson Luke , Cotter James D. , Lucas Samuel , Ogoh Shigehiko , George Keith , Ainslie Philip N.
Published: March 2007

We examined potential mechanisms (autonomic function, hypotension, and cerebral hypoperfusion) responsible for orthostatic intolerance following prolonged exercise. Autonomic function and cerebral hemodynamics were monitored in seven athletes pre-, post- (<4 h), and 48 h following a mountain marathon [42.2 km; cumulative gain ∼1,000 m; ∼15°C; completion time, 261 ± 27 (SD) min]. In each condition, middle cerebral artery blood velocity (MCAv), blood pressure (BP), heart rate (HR), and cardiac output (Modelflow) were measured continuously before and during a 6-min stand. Measurements of HR and BP variability and time-domain analysis were used as an index of sympathovagal balance and baroreflex sensitivity (BRS). Cerebral autoregulation was assessed using transfer-function gain and phase shift in BP and MCAv. Hypotension was evident following the marathon during supine rest and on standing despite increased sympathetic and reduced parasympathetic control, and elevations in HR and cardiac output. On standing, following the marathon, there was less elevation in normalized low-frequency HR variability ( P < 0.05), indicating attenuated sympathetic activation. MCAv was maintained while supine but reduced during orthostasis postmarathon [−10.4 ± 9.8% pre- vs. −15.4 ± 9.9% postmarathon (%change from supine); P < 0.05]; such reductions were related to an attenuation in BRS ( r = 0.81; P < 0.05). Cerebral autoregulation was unchanged following the marathon. These findings indicate that following prolonged exercise, hypotension and postural reductions in autonomic function or baroreflex control, or both, rather than a compromise in cerebral autoregulation, may place the brain at risk of hypoperfusion. Such changes may be critical factors in collapse following prolonged exercise.
Laser Treatment in Diabetic Retinopathy
Authors: Neubauer Aljoscha S. , Ulbig Michael W.
Published: March 2007

Diabetic retinopathy is a leading cause of visual impairment and blindness in developed countries due to macular edema and proliferative diabetic retinopathy (PDR). For both complications laser treatment may offer proven therapy: the Diabetic Retinopathy Study demonstrated that panretinal scatter photocoagulation reduces the risk of severe visual loss by >50% in eyes with high-risk characteristics. Panretinal scatter coagulation may also be beneficial in other PDR and severe nonproliferative diabetic retinopathy (NPDR) under certain conditions. For clinically significant macular edema the Early Treatment of Diabetic Retinopathy Study could show that immediate focal laser photocoagulation reduces the risk of moderate visual loss by at least 50%. When and how to perform laser treatment is described in detail, offering a proven treatment for many problems associated with diabetic retinopathy based on a high evidence level.
Evidence-Based Therapy of Diabetic Retinopathy
Authors: Hoerle S. , Kroll P.
Published: March 2007

Introduction: Evidence-based medicine is often misunderstood as ‘cookbook medicine with standard recipes’ that does not take clinical experience into account. It is, however, supposed to be a basis for decision making in caring for individual patients under consideration of patients’ preferences. This seems to be very important, since diabetic retinopathy continues to be the most frequent cause of vision loss in working age adults with negative consequences for patients’ quality of life and for health economics. Materials and Methods: The most important evidence-based therapy for diabetic retinopathy and maculopathy is laser coagulation. Vitrectomy for proliferative stages has also been proven effective by clinical studies. For more recent treatment options like triamcinolone injection and vitrectomy for diabetic macular edema there is a lower level of evidence so far. Results: The Diabetic Retinopathy Study was the first to show the effectiveness of panfundus laser coagulation for a larger group of patients. The Early Treatment Diabetic Retinopathy Study in turn serves as a basis for laser coagulation of retinopathy and maculopathy. The Diabetic Retinopathy Vitrectomy Study could show the advantages of timely vitrectomy. Both the Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study could show the value of intensive blood glucose control. Discussion: Evidence-based medicine on the basis of the studies mentioned above is practiced quite self-evidently in ophthalmo-diabetology. It should be regarded as a helpful tool for special therapeutic situations which still leaves room for one’s personal clinical experience to be included. It is somewhat problematic that the term evidence-based medicine seems to be restricted to the results of large randomized studies, because even special problems and very individual, difficult therapeutic questions can be placed on an evidence-based foundation, although at a lower level of evidence, using today’s modern means of literature research.
Applications and Implications of Advances in Human Genetics: Perspectives from a Group of Black Americans
Authors: Sheldon Jane P. , Epstein Jayaratne Toby , Feldbaum Merle B. , DiNardo Courtney D. , Petty Elizabeth M.
Published: March 2007

Objectives: We explored the opinions of 40 Black Americans regarding: (1) what they thought most Blacks and Whites believe about genetic causes for perceived race differences in human traits, and (2) the impact of genetic science on them, their families, and Black people. Methods: We conducted in-depth telephone interviews with 40 self-identified Black men and women. Transcripts of the interviews were recorded and examined for common themes. Results: The majority of our respondents felt that most Whites, unlike most Blacks, attribute differences between these groups to genetic factors. Many in our sample felt that genetic advances may provide benefits in the area of health care, but many also recognized potential harm. Conclusions: Our results provide a glimpse as to what some Blacks believe about genetic science in the context of racial issues.
Knowledge of and Attitudes about Alzheimer Disease Genetics: Report of a Pilot Survey and Two Focus Groups
Authors: Moscarillo T.J. , Holt H. , Perman M. , Goldberg S. , Cortellini L. , Stoler J.M. , DeJong W. , Miles B.J. , Albert M.S. , Go R.C.P. , Blacker D.
Published: March 2007

Objectives: In preparation for the development of an educational intervention on Alzheimer disease (AD) genetics, we undertook a pilot survey of knowledge in this area and attitudes toward genetic testing for AD among individuals with a family history of AD. Methods: For the pilot study, we administered a 30-min questionnaire to 57 unaffected individuals from a genetic linkage study. For the focus groups, we interviewed two groups of subjects, ages 44–70 years, with a family history of AD, one of 10 Caucasians and the other of 6 African-Americans. Results: The pilot study showed that there was limited knowledge of genetics overall and AD genetics in particular, considerable concern about personal risk, and little knowledge of or interest in genetic testing for the disease. The focus groups reinforced and fleshed out these impressions and highlighted the importance of caregiving experience in the attitudes toward personal risk for AD. Conclusions: These results underscore the value of genetics education for this and other complex diseases and suggest specific foci for educational interventions.
Is Cystic Fibrosis Carrier Screening Cost Effective?
Authors: Wei S. , Quigg M.H. , Monaghan K.G.
Published: March 2007

Between 2001 and 2005, 6,166 females underwent cystic fibrosis (CF) carrier screening at our institution. Only 36% were Caucasian. We identified 143 carrier females and subsequently tested 85 of their partners. The observed carrier frequency was not significantly different than expected for any racial or ethnic group tested. We identified 6 positive couples (5 Caucasian, 1 Arab American) and 1 affected fetus. In just under 4 years, our institution spent approximately USD 334,000 on CF population screening. Comparing this to the lifetime medical cost for a CF patient, CF population-based carrier screening is cost effective at our institution, despite the high number of non-Caucasians being screened.
Genetic Alterations in Sporadic and Hereditary Colorectal Cancer: Implementations for Screening and Follow-Up
Authors: Souglakos John
Published: March 2007

The genetics underlying an inherited predisposition to cancer are rapidly being uncovered. This fact may ultimately lead to the routine use of molecular tools to diagnose these disorders, and establish interventions to prevent the development of cancer. Among the multiple cancer family syndromes, several are known to be associated with the development of colon cancer. These disorders may be diagnosed during evaluation of the index patient or during screening of family members who are at risk. Although the effectiveness of screening and surveillance strategies is unproven in controlled clinical trials for any of these syndromes, the high cancer risk warrants screening, and reasonable recommendations can be made. Several other genetic syndromes are associated with gastrointestinal polyposis. The risk of colon cancer in these diseases is uncertain, and may not be increased and they are not mentioned in this review. Examples include Cowden disease, intestinal ganglioneuromatosis, Ruvalcaba-Myhre-Smith syndrome, Devon family syndrome, and Cronkite-Canada syndrome.
Detection of Colorectal Cancer Hepatic Metastases with Contrast-Enhanced Ultrasound: Comparison with Conventional B-Mode Ultrasound
Authors: Yarmenitis S.D. , Karantanas A. , Bakantaki A. , Papantoniou Y. , Gourtsoyiannis N.
Published: March 2007

The aim of this study was to assess whether contrast-enhanced ultrasound (CE-US) could provide improved diagnostic information in detecting liver metastases from colorectal cancer as compared to B-mode non-enhanced ultrasound (B-US). 32 patients (M/F 23/9, age range 48–82 years, mean 58.2 years) under chemotherapy for colorectal cancer were examined with B-US and CE-US using a second-generation ultrasound contrast agent and a dedicated protocol for contrast detection. The presence of focal liver lesions along with the number, size, pre- and post-contrast sonographic features were recorded digitally. Lesion conspicuity with a three-grade scoring scale was performed on both techniques and contrast intensity measurements were calculated for each focal lesion. CE-US detected 17% more metastases in patient-by-patient and lesion-by-lesion analysis. A statistically significant difference was found between the scoring mean values with regard to conspicuity of the lesions. Accurate characterization of the liver lesions was achievable only with contrast-enhanced technique. A quantitative contrast intensity measurement method confirmed the invariably washing-out vascular pattern in all metastases at sinusoidal-parenchymal liver phase. In conclusion, CE-US is superior to B-US and provides an effective tool in the investigation of colorectal cancer liver metastases.
WITHDRAWN: Irinotecan plus Weekly 5-Fluorouracil and Leucovorin as Salvage Treatment for Patients with Metastatic Colorectal Cancer: A Phase II Trial
Authors: Souglakos J. , Vardakis N. , Androulakis N. , Kakolyris S. , Kourousis C. , Mavroudis D. , Pallis A. , Agelaki S. , Kalbakis K. , Georgoulias V.
Published: March 2007

Previously published as: J BUON 2005;10(1):47–52
Variations in Biological and Immunological Activity of Growth Hormone during the Neonatal Period
Authors: Pagani S. , Chaler E.A. , Radetti G. , Travaglino P. , Meazza C. , Bozzola E. , Sessa N. , Belgorosky A. , Bozzola M.
Published: March 2007

Background/Aims: It was postulated that a high growth hormone (GH) bioactivity might explain the rapid growth rate of neonates. The aim of this study is to verify changes in serum GH biological potency (Bio-/Immuno-GH ratio) and their effects on serum growth factors during the first month of life in term and preterm babies. Methods: Blood samples were collected from 10 small-for-gestational-age preterm (SGAPT), 17 appropriate for gestational age preterm (AGAPT) and 26 AGA term (T) neonates on days 4, 15 and 30 of life to evaluate serum GH values measured by IFMA (IFMA-GH) and bioassay (Bio-GH), serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3). Results: High serum Bio-GH values on the first few days of life correspond to high IFMA-GH values, suggesting full biological potency of circulating GH. Furthermore, IGF-I/IGFBP-3 molar ratio values in preterm babies were higher than in full-term infants. Conclusions: These data confirmed the hypothesis that the higher growth velocity in the first month of life of preterm neonates is due to an increased bioavailability of IGF-I. A progressive maturation of the hypothalamic-pituitary-IGF-I axis without any alteration in the GH biological potency seems to underpin the increase of the growth factors early in life.
CCI-779 plus Cisplatin Is Highly Effective against Human Melanoma in a SCID Mouse Xenotranplantation Model
Authors: Thallinger C. , Poeppl W. , Pratscher B. , Mayerhofer M. , Valent P. , Tappeiner G. , Joukhadar C.
Published: March 2007

Background: This study set out to investigate the antitumor effects of a treatment strategy combining the mTOR inhibitor CCI-779 with cisplatin in vitro and in a human melanoma SCID mouse model. Methods: In vitro 518A2, Mel-JUSO or 607B cell lines were incubated with CCI-779, cisplatin and CCI-779 plus cisplatin. Based on these results, a 4-group, parallel, controlled experimental study design was initiated in vivo. SCID mice were injected with melanoma cells, and after the development of tumors the mice received daily injections of CCI-779 or solvent. On treatment days 2 and 6 cisplatin or mock solution were administered. Results: In vitro a synergistic antitumor effect was observed for the treatment regimen of CCI-779 plus cisplatin. In SCID mice after 2 weeks of therapy with CCI-779 plus cisplatin 4 of 6 tumors of the 518A2 cell line were completely eradicated. In the two remaining 518A2 xenografts this treatment strategy reduced the tumor weight by 94 ± 9% compared to solvent. CCI-779 plus cisplatin also exerted a significant antitumor effect in Mel-JUSO and 607B xenografts compared to mock-treated animals. Conclusion: We provide circumstantial evidence that the use of CCI-779 plus cisplatin might qualify as a promising strategy in the treatment of human melanoma.
Use of Tissue Oxygenation Index and Fractional Tissue Oxygen Extraction as Non-Invasive Parameters for Cerebral Oxygenation
Authors: Naulaers Gunnar , Meyns Bart , Miserez Marc , Leunens Veerle , Van Huffel Sabine , Casaer Paul , Weindling Michael , Devlieger Hugo
Published: March 2007

Objective: To evaluate the relation between cerebral tissue oxygenation index (TOI), measured with spatially resolved spectroscopy (SRS), and the different oxygenation parameters. To evaluate the relation between a new parameter named fractional tissue oxygen extraction (FTOE) and the cerebral fractional oxygen extraction (FOE). Methods: Six newborn piglets were measured at 33, 35, and 37°C and in hypocapnia. Mean arterial blood pressure (MABP), haemoglobin (Hb), peripheral oxygen saturation (SaO2) and PaCO2 were measured at each step. Cerebral blood flow (CBF) was measured by injection of coloured microspheres into the left atrium. Jugular bulb oxygen saturation (JVS), cerebral arterial and venous oxygen content (CaO2 and CvO2) and FOE were calculated. TOI of the brain was calculated and FTOE was introduced as (SaO2 – TOI)/SaO2. The correlation was calculated with an ANCOVA test. Results: There was a positive correlation (R = 0.4 and p = 0.011) between TOI and JVS. No correlation was found with CBF, MABP or Hb. There was a positive correlation between PaCO2 and cerebral TOI (R = 0.24 and p = 0.03). FTOE correlated well with FOE (R = 0.4 and p = 0.016) and there was a negative correlation between FTOE and PaCO2 (R = 0.24, p = 0.03). Conclusion: The measurement of TOI and FTOE by SRS correlated well with the cerebral venous saturation and FOE, respectively.
Present and Future Developments of Stereotactic Technology
Authors: Kelly Patrick J. , Kall Bruce A. , Goerss Stephan , Earnest Franklin
Published: March 2007

Incorporation of a surgical computer system into stereotactic methodology provides the facility for efficient utilization of the multiple data bases at the disposal of the modern stereotactician. Computed tomography, magnetic resonance imaging, and digital fluoroscopy data gathered in stereotactic conditions are digitized into a stereotactic surgical matrix for surgical planning and interactive surgical procedures. The advantages of this system are illustrated in stereotactic biopsy, interstitial irradiation, and laser resections of intracranial tumors.
Real-Time Three-Dimensional Graphic Reconstructions Using Brown-Roberts-Wells Frame Coordinates in a Microcomputer Environment
Authors: Heilbrun M. Peter , Brown Russell A. , McDonald Paul R.
Published: March 2007

A desktop microcomputer environment that utilizes Brown-Roberts-Wells (BRW) frame coordinates for creation of three-dimensional depiction of operator-defined intracranial structures has been developed. The system allows direct reading of Siemens CT scan images from a floppy disc, structural edge definition, and reconstruction of defined images. The system is used in the operating room to view scans, perform Standard BRW stereotactic functions, and create three-dimensional graphics for such tasks as defining tumor margins, conceptualizing positional relationships of intracranial structures, and radiation planning.
X-Ray and Magnetic Resonance Stereotaxy for Functional and Nonfunctional Neurosurgery
Authors: Birg W. , Mundinger F. , Mohadjer M. , Weigel K. , Fuermaier R.
Published: March 2007

By means of new plastic stereotactic ring and head fixers, stereotactic procedures can be combined with MRI, with stereotactic coordinates obtained from the MRI images. The method was rechecked against CT stereotaxy and shows a good correspondence of the target coordinates. With MRI stereotaxy, structures near boney regions will be more accessible than with CT stereotaxy. Moreover, the MRI procedure seems to have advantages for functional therapy without the necessity of contrast ventriculography.
Computer Tomography-Controlled Stereotactic Surgery
Authors: Matsumoto Keizo , Shichijo Fumio , Masuda Tsutomu , Miyake Hajime
Published: March 2007

In computed tomography (CT)-controlled stereotactic surgery, the coordinate system of the CT scanner is applied to determine the target depth and direction as well as for readjustment of final probe direction. This method can be used for all types of stereotactic surgery for the brain.
Use of the Brown-Roberts-Wells Stereotactic Frame for Functional Neurosurgery
Authors: Hadley Mark N. , Shetter Andrew G. , Amos M. Rob
Published: March 2007

The Brown-Roberts-Wells (BRW) stereotactic unit has proven itself to be a highly accurate instrument for biopsying or locating pathologic intracranial lesions based on CT scan information. We utilized the BRW frame to select 18 target sites in 12 patients undergoing functional stereotactic procedures. Two patients had bilateral cingulumotomies, 5 had thalamotomies for movement disorders, and 5 underwent electrode implantations for the treatment of chronic pain. Stereotactic frame settings were determined using a positive contrast ventriculogram, orthogonal radiographs, and a computer program provided with the BRW system. In addition, attempts were made to select targets based on CT scan landmarks alone, and these were compared to those derived using ventriculography.We found the BRW frame to be a satisfactory device for performing functional neurosurgical procedures based on ventriculographic landmarks. Coordinates derived from CT scans were similar to those obtained with ventriculography, but were not accurate enough to permit the use of CT scanning as the sole means of target identification. Although future improvements in imaging techniques and computer software are likely to occur, our experience supports ventriculography as the current method of choice for the precise localizafion of functional targets with the BRW stereotactic system.
Simultaneous Recordings in the Human Thalamus and Cortex of an Early Evoked Component
Authors: Albe-Fessard D. , Tasker R.R. , Yamashiro K. , Chodakiewitz J. , Dostrovsky J.
Published: March 2007

Evoked potentials have been simultaneously recorded in 9 patients at thalamic and scalp cortical levels. The similarity of wave characteristics at both levels seems to demonstrate the origin in a thalamic near-field of the P14–16 cortical wave. A thalamic origin of at least a part of N18–20 is also indicated.
Stereotactic Radiosurgery Utilizing a Linear Accelerator
Authors: Colombo F. , Benedetti A. , Pozza F. , Zanardo A. , Avanzo R.C. , Chierego G. , Marchetti C.
Published: March 2007

The authors have developed a radiosurgical technique based on multiple arc irradiations. The target is fixed to the rotational isocenter of a Varian 4 MV linear accelerator. The first irradiation is carried out while the radiating source is rotating on a 100–140° arc. The patient is then rotated around a vertical axis passing through the target, and arc irradiations are repeated in different angular positions. By this technique it is possible to obtain very steep dose gradients at the borders of the target volume. High doses are usually delivered in two shots.
Stereotactic Intracavitary Irradiation of Cystic Neoplasms of the Brain
Authors: Lunsford Dade , Gumerman L. , Levine G.
Published: March 2007

Ten patients with intracranial cystic tumors underwent stereotactic intracavitary irradiation using 32P colloidal chromic phosphate. Accurate dosimetry (25,000–30,000 rad to the cast wall) was achieved by volume estimation using computed tomography. Between 1 and 15 months after surgery both craniopharyngioma and astrocytoma cysts regressed. Neurological, visual, and endocrinological deficits either stabilized or improved. Intracavitary irradiation should be the primary method of treating solitary cystic tumors of the brain.
Changes in Local Cerebral Glucose Utilization Induced by Electrical Stimulation of the Parafascicular and VPL Thalamic Nuclei in Rats
Authors: Aiko Yasutaka , Shima Fumio , Kato Motohiro , Kitamura Katsutoshi
Published: March 2007

A parallel bipolar stimulating electrode was stereotactically inserted in Pf and VPL. The parameter of Pf stimulating was adjusted so the withdrawal response of rats to tail-pinch was diminished. The stimulation started immediately before 14C-deoxyglucose injection and lasted for 45 min, following which the rat was sacrificed. Coronal sections of the frozen brain were made and autoradiographs of these sections were prepared. LCGU was measured by Sokoloff’s 2-deoxyglucose method.
Clinicoanatomical Study of Thalamic Stimulation for Pain Relief
Authors: Kuroda R. , Nakatani J. , Ioku M. , Koshino K.
Published: March 2007

Our small experiences with electrical stimulation in the VPL and VPM for dysesthetic pain show that it provoked only paresthesia and induced some relief of pain. It does not increase the beta-endorphin level in CSF. To clarify the anatomical substrata in VPL stimulation, neuroanatomical studies were done about the inputs to VPL in man, monkey and cat by the Fink-Heimer method. The spinothalamic tract terminates in VPL in a patchy fashion in the monkey. The corticothalamic fibers from SI and SII cortex project to VPL and VPM in somatotopical organization in the cat. SI and SII cortices have reciprocal connections, in addition to projections to area 5 or SIII cortex. The corticofugal fibers to the magnocellular and gigantocellular tegmental fields are suggested in addition to the dorsal column nuclei, spinal trigeminal nuclei and spinal posterior horn in cat. The medial lemniscus input to VPL and the above neural circuits are thought to be associated with VPL stimulation.
Chronic Stimulation of the Septal Area for the Relief of Intractable Pain
Authors: Schvarcz Jorge R.
Published: March 2007

Although brain stimulation techniques have changed the treatment of pain, their rationale has not yet been fully proved, and their clinical results are still frequently erratic or contradictory. In an attempt to provide alternate sites for stimulation, 10 patients were, in addition to conventional targets, chronically implanted at the septal area. Satisfactory relief of dysesthetic pain was induced by septal stimulation in 60% of the cases overall, without untoward effects. The follow-up ranged from 1 to 42 months. The available data conceivably suggest other mechanisms than the presumed exclusive activation of opiomimetic structures. They also seem to indicate that the septal area may be a suitable target for chronic stimulation.
The Spread of Somatosensory-Evoked Potentials Within the Nervous System
Authors: Sólyom A. , Tóth S. , Holczinger I. , Vajda J. , Tóth Z. , Kálmánchey R.
Published: March 2007

Four thalamic and cortical recordings were carried out in 5 patients. The thalamic-evoked potentials were typical and revealed a triphasic complex, but their latencies showed a relatively high Standard deviation. They could be divided into two groups according to their latencies, both of which had low SD. These data suggested that there could be two types of latency of thalamic SEP, because the 4 patients’ body sizes were very similar. More detailed surface, cortical and depth recordings are needed to resolve these questions.
An Animal Model for Neuron-Specific Spinal Cord Lesions by the Microinjection of N-Methylaspartate, Kainic Acid, and Quisqualic Acid
Authors: Pisharodi Madhavan , Nauta Haring J.W.
Published: March 2007

It has been shown that N-methylaspartate (NMA), kainic acid (KA), and quisqualic acid (QA) can produce preferential neuronal damage in various parts of the striatum, hippocampus, and thalamus with relative sparing of axons in transit. Thus far, the evidence that axons in transit escape destruction has been based largely on histological observations. To test the functional integrity of axons in passage, we made unilateral lesions with these agents in the cervical spinal cord of rats and compared the subsequent functional deficits with those seen after spinal cord hemisections. Observations were made in 14 rats. In each case, a laminectomy at the C6-C7 level was performed under general anesthesia. Animals receiving microinjections of KA, QA, or NMA showed motor and sensory deficits only in the ipsilateral forepaw and remained able to use the hindpaws normally. By contrast, animals undergoing spinal cord hemisection developed obvious motor deficits in the ipsilateral hindpaw in addition to the deficits in the forepaw. Histological observations of the spinal cords confirmed an extensive gray matter destruction with relative preservation of the long tracts in animals injected with KA, QA, and NMA. In addition, it was noted that spinal cord neurons appear relatively less sensitive to KA and more sensitive to QA than neurons in the thalamus, striatum, or hippocampus. The possible application of these findings for the production of dorsal root entry zone lesions will be discussed.
Woroschiloff’s Locating Device for Interventions on the Spinal Cord and lts Influence on Spinal Stereotaxis
Authors: Nádvornik P.
Published: March 2007

111 years ago the first locating device for the spinal cord was constructed, which became the basis for the contemporary spinal cord stereotaxy. Woroschiloff invented this device to operate stereotactically in different spinal cord segments. Nowadays only the fixation of the spinal cord stereotactic device to the wound retractor has changed from his concept, and control of the surgical instrument has been improved in three perpendicular planes corresponding to the special stereotactic maps of the human spinal cord.
Cerebral-Evoked Responses Elicited by Direct Stimulation of the Lateral Spinothalamic Tract in the Human
Authors: Taira T. , Amano K. , Kawamura H. , Tanikawa T. , Kitamura K.
Published: March 2007

The authors recorded cerebral-evoked responses elicited by direct stimulation of the human lateral spinothalamic tract (LST) during percutaneous cordotomy to investigate central conduction of noxious stimuli. These responses consisted of four negative potentials, peak latency being 3.8 (N1), 8.4 (N2), 12.2 (N3) and 21.9 (N4) ms respectively. N1 showed wide distribution over the scalp and was considered to be of subcortical origin. N2–N4 were distributed in both the temporal and central area. The different distribution pattern of N2–N4 from conventional somatosensory-evoked potential suggested a different projection of LST from the medial lemniscus system.
A Method for Bulbospinal Trigeminal Nucleotomy in the Treatment of Facial Deafferentation Pain
Authors: Siqueira José M.
Published: March 2007

Many types of facial pain are difficult to treat, such as postherpetic, posttraumatic, or pain following denervation procedures used in the treatment of trigeminal neuralgia (anesthesia dolorosa), all of which involve deafferentation of the spinal trigeminal nucleus.
Stereotactic Pallidotomy in Extrapyramidal Disorders
Authors: Burzaco J.
Published: March 2007

The results of stereotactic pallidotomy in 37 patients with extrapyramidal disorders are presented. All patients had the same RF lesions and target coordinates. The patients are classified into 5 groups according to the clinical picture. These results are compared with those obtained by thalamotomy in a similar group of patients. The main indications for pallidotomy are given. The spatial representation of globus pallidus medialis according to Andrews and Watkins, Talairach and the author are shown and their differences discussed.