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Biomedical subjects

J Haller

Publications and source records attributed to J Haller.

At least 37 records · Page 2Linked to original sources

Ultrasonographic guidance for spinal extracranial radiosurgery: technique and application for metastatic spinal lesions.

OBJECT: The relatively stationary anatomy of the intracranial compartment has allowed the development of stereotactic radiosurgery as an effective treatment option for many intracranial lesions. Difficulty in accurately tracking extracranial targets has limited its development in the treatment of these lesions. The ability to track extracranial structures in real time with ultrasound images allows a system to upgrade and interface pretreatment volumetric images for extracranial applications. In this report the authors describe this technique as applied to the treatment of localized metastatic spinal disease. METHODS: The extracranial stereotactic system consists of an optically tracked ultrasonography unit that can be registered to a linear accelerator coordinate system. Stereotactic ultrasound images are acquired following patient positioning, based on a pretreatment computerized tomography (CT) simulation. The soft-tissue shifts between the virtual CT-based treatment plan and the actual treatment are determined. The degree of patient offset is tracked and used to correct the treatment plan. The ultrasonography-based stereotactic navigation system is accurate to within an approximate means of 1.5 mm based on testing with an absolute coordinate phantom. A radiosurgical treatment was delivered using the system for localization of a metastatic spinal lesion. Compared with the virtual CT simulation, the actual treatment plan isocenter was shifted 12.2 mm based on the stereotactic ultrasound image. The patient was treated using noncoplanar beams to a dose of 15.0 Gy to the 80% isodose shell in a single fraction. CONCLUSIONS: A system for high-precision radiosurgical treatment of metastatic spinal tumors has been developed, tested, and applied clinically. Optical tracking of the ultrasonography probe provides real-time tracking of the patient anatomy and allows computation of the target displacement prior to treatment delivery. The results reported here suggest the feasibility and safety of the technique.

Antineoplastic Combined Chemotherapy Protocols↗

The effect of glucocorticoids on the anxiolytic efficacy of buspirone.

RATIONALE: The serotonergic system and the hypothalamus-hypophysis-adrenocortical axis reciprocally influence each other. Therefore, the interaction between stress and serotonergic anxiolytics should be of major concern for both laboratory investigations and clinical treatment. OBJECTIVES: We have studied the effects of the serotonergic anxiolytic buspirone in rats in which basal levels of glucocorticoids were low and stable, while acute stress reactions were inhibited or exogenously induced. METHODS: Rats were adrenalectomised. Subcutaneous corticosterone pellets maintained basal glucocorticoid concentrations while acute changes were mimicked by corticosterone injections. Anxiety was assessed by the social interaction test. Temporal changes were evaluated by submitting rats to the same manipulations three times at two-day intervals. RESULTS: Buspirone applied to animals with stable and low plasma glucocorticoid concentrations induced a dramatic increase in social interactions. A slight locomotor suppressive effect was also noticed. The effects of buspirone proved to be stable over time in these animals. Acute treatment with corticosterone doubled the locomotor suppressive effects of buspirone and reversed its anxiolytic effects: the buspirone-corticosterone combination was anxiogenic after the first application. During the second and third treatment, the impact of corticosterone on buspirone efficacy gradually decreased, but the combined treatment remained about half as effective in reducing anxiety as buspirone alone.

Adrenalectomy↗

The link between stress and the efficacy of anxiolytics. A new avenue of research.

There is an important discrepancy between animal models of anxiety and human anxiety patients: while experimental animals are usually unstressed, patients usually have a long history of stress. Stressful life events not only contribute to the development and/or maintenance of mood disorders in humans but also affect the efficacy of anxiolytic treatment in both animals and humans. The effects are not trivial: sometimes stress may totally abolish the effects of certain anxiolytics. Therefore, the relationship between stress exposure and anxiolytic efficacy should be an important area of research and drug development. There are several benefits that may be derived from similar studies: (i) the effect of stress may unravel yet unknown aspects of the mechanism of action of different drugs; (ii) the relevance of laboratory studies would increase; and (iii) laboratory findings may provide cues regarding the clinical use of drugs.

Anti-Anxiety Agents↗

Non-genomic effects of glucocorticoids in the neural system. Evidence, mechanisms and implications.

Complementing the classical concept of genomic steroid actions, here we (i) review evidence showing that important neural effects of glucocorticoids are exerted by non-genomic mechanisms; (ii) describe known mechanisms that may underlie such effects; (iii) summarize the functions and implications of non-genomic mechanisms and (iv) outline future directions of research. The role of non-genomic mechanisms is to shape the response of the organism to challenges that require a substantial reorganization of neural and somatic functions and involve massive behavioral shifts. Non-genomic effects may (i) prepare the cell for subsequent glucocorticoid-induced genomic changes, (ii) bridge the gap between the early need of change and the delay in the expression of genomic effects and (iii) may induce specific changes that in some instances are opposite to those induced by genomic mechanisms. The latter can be explained by the fact that challenging situations require different responses in early (acute) and later (chronic) phases. Data show that non-genomic mechanisms of glucocorticoid action play a role in both pathological phenomena and the expression of ameliorative pharmacological effects. Non-genomic mechanisms that underlie many glucocorticoid-induced neural changes constitute a for long overlooked controlling factor. Despite the multitude and the variety of accumulated data, important questions remain to be answered.

Animals↗

Deviant forms of aggression in glucocorticoid hyporeactive rats: a model for 'pathological' aggression?

Deviant forms of aggressiveness have been associated with low plasma glucocorticoid concentrations in humans. Here, we report data on the development of aggressive behaviour in rats in which glucocorticoid secretion was inhibited by adrenalectomy. Such rats were compared with both sham operated rats and adrenalectomized rats in which the fight-induced elevation of plasma glucocorticoids was mimicked by acute injections. Low and stable corticosterone plasma concentrations were maintained by subcutaneous glucocorticoid pellets in adrenalectomized rats. The development of aggressive behaviour was followed over three trials performed at 2-day intervals. Adrenalectomy lead to high aggressiveness already at the first encounter, a decreased threatening (attack signalling) behaviour and a change in attack targeting. While control rats targeted biting attacks towards less vulnerable dorsal parts of the opponent's body, adrenalectomized rats attacked the head frequently. Corticosterone injections that mimicked the fight induced adrenocortical reaction abolished this behavioural pattern. Thus, a reduced responsiveness of the adrenocortical system may be causally linked to deviant forms of aggression in rats.

Adrenalectomy↗

Accessory salivary tissue in the mylohyoid boutonnière: a clinical and radiologic pseudolesion of the oral cavity.

BACKGROUND AND PURPOSE: Though classically depicted as a continuous muscular barrier between the sublingual and submandibular spaces, the mylohyoid muscle is often discontinuous. These areas of discontinuity may contain fat, blood vessels, salivary tissue, or combinations thereof that may be mistaken both clinically and radiologically for pathologic abnormalities. We sought to demonstrate the prevalence and radiologic appearance of dehiscence of the mylohyoid muscle. METHODS: One hundred axial, contrast-enhanced CT studies of the neck, obtained over a 10-month period, were retrospectively reviewed. Inclusion criteria included 3-mm-thick slices and absence of pathologic abnormalities or surgical changes in the oral cavity. Scans were assessed for the presence and contents of mylohyoid defects such as accessory salivary tissue, defined as nonlymphoid tissue within defects in the mylohyoid, having attenuation and enhancement characteristics similar to those of orthotopic sublingual and submandibular salivary tissue. RESULTS: Mylohyoid defects were identified in 77 of 100 individuals. The deficiencies were bilateral in 67% and unilateral in 33%. Accessory salivary tissue was identified in 37 of 100. Fat and blood vessels were commonly identified within the mylohyoid defects. Sixty-one percent of the defects contained only fat. Thirty-five percent of the defects contained blood vessels. CONCLUSION: Deficiencies in the mylohyoid muscle were visible in 77% of individuals who underwent scanning. The defects may contain fat, blood vessels, salivary tissue, or all three characteristics. Accessory salivary tissue was identified in 37% of individuals who underwent scanning. Recognition of mylohyoid deficiencies and the typical appearance of accessory salivary tissue will allow accurate diagnosis of this benign, anatomic variant.

Adipose Tissue↗

Fruit and vegetable servings in ten SENECA towns and the impact of the midday meal.

OBJECTIVE: Assessing fruit, vegetable and potato servings in relation to meal pattern. DESIGN: Longitudinal study including dietary assessment in 1988/9 and 1993. SETTING: 10 small European towns. SUBJECTS AND METHODS Counting the number of fruit, vegetable and potato servings in dietary records of 1275 men and women born 1913 to 1918. RESULTS: In the northern towns less than 12% of the subjects consumed 5 or more fruit and vegetable servings and up to 84% consumed only 2 or less servings per day. In the southern towns more than 30% consumed 5 or more servings and less than 20% had only 2 or less servings per day. In 9 of 10 towns a cooked meal at midday contained more fruit and vegetable servings than a cooked meal eaten in the evening. The weight of one serving as calculated from the regression line was 137 g for fruit, 145 g for vegetables and 196 g for potatoes. A significant relationship was found between antioxidant status and vegetables with regard to the number of servings but not to the intake in gram. CONCLUSIONS: RESULTS strengthen the hypothesis that a cooked meal at midday mediated a healthier diet than a cooked meal in the evening. Number of fruit and vegetable servings is a more accurate indication of diversity in vegetable consumption than intake in gram.

Aged↗

Effects of two acute stressors on the anxiolytic efficacy of chlordiazepoxide.

RATIONALE: Limited published data show that drug efficacy can be influenced by stressors. Thus, drug testing in stressed animals may unravel important variables determining drug effects. OBJECTIVES: The experiments tested the anxiolytic efficacy of the benzodiazepine chlordiazepoxide under conditions of acute stress. METHODS: Previously group-housed rats were injected with 0, 3, and 10 mg/kg chlordiazepoxide, thereafter being exposed to two types of stress: novelty (transfer to an individual cage) and social defeat. Controls were group-housed animals. Anxiety was assessed on the plus maze. RESULTS: Speed of locomotion was increased by chlordiazepoxide in both stressed groups but not in controls. Chlordiazepoxide exerted a marked reduction in anxiety in controls and defeated rats but not in novelty exposed animals. The effects of novelty exposure were considerably weaker when drug testing was performed 24 h later. CONCLUSIONS: Stress exposure had an impact on the behavioral effects of chlordiazepoxide. Changes in locomotor activity induced by the drug appear to depend on the presence of a stressor, while anxiolytic efficacy appears to depend on the type of the stressor. Since it has been shown that drug efficacy changes in a variety of behavioral situations and drug classes, it is suggested that experimental background is an important variable in determining behavioral effects of drugs.

Acute Disease↗

Surgical management of recurrent iris stromal cyst.

PURPOSE: To report the clinical history and surgical management of recurrent congenital iris stromal cyst. METHOD: Case report. Argon laser endophotocoagulation and cryotherapy were used to treat a recurrent iris stromal cyst in an 18-month-old boy. RESULTS: At 43 months of follow-up, there was no recurrence or evidence of epithelial ingrowth. CONCLUSION: Treatment with argon laser endophotocoagulation and cryotherapy resulted in complete resolution of a recurrent congenital iris cyst.

Cryotherapy↗

Distribution of serum apolipoproteins A-I and B and lipoprotein(a) in European elderly. The SENECA study.

The purpose of this study is to describe sex and geographic differences in apolipoproteins (apo) A-I and B and lipoprotein(a) [Lp(a)] concentrations in elderly Europeans. Subjects were 2164 elderly participants of the SENECA study from different regions of Europe. Sera for apo A-I, apo B, and Lp(a) measurement were available for 1703 individuals. In men, mean values ranged from 1.38 to 1.79 g/l for apo A-I, 1.03-1.36 g/l for apo B, and 0.26-0.67 g/l for Lp(a). In women, mean values ranged from 1.54 to 1.98, 1.20-1.51, and 0.26-0.68 g/l for apo A-I, apo B, and Lp(a), respectively. A comparison of northern (Norway, Denmark, Netherlands), middle (France, Switzerland), and southern (Portugal, Spain, Italy, Greece) communities showed a less atherogenic profile in the south, including lower LDL cholesterol, apo B, TC/HDL cholesterol ratio, and apoB/apo A-I ratio. Men, but not women, also had significantly higher HDL cholesterol and apo A-I concentrations in the South. Paradoxically, Lp(a) concentrations were generally high among all elderly and were significantly higher in the southern communities. These data show that the elderly in Europe are very heterogeneous with respect to plasma lipoproteins, including apo A-I, apo B, and Lp(a).

Aged↗

Fast algorithm for soft straightening of the colon.

RATIONALE AND OBJECTIVES: In this study, the authors developed a fast algorithm for soft straightening of the colon with computed tomographic data that greatly accelerates the unraveling process based on the interpolation of representative electric force lines. MATERIALS AND METHODS: Each curved cross section of the colon is defined by electric force lines of a common origin on an electrically charged central path and is constructed by interpolating most of these force lines from a limited number of representative force lines that are traced directly. Both a synthetic colon phantom and a colon in a living patient were used to demonstrate the feasibility of the fast interpolation algorithm compared with direct implementation for soft straightening of the colon. RESULTS: The interpolation-based soft-straightening algorithm ran approximately 40 times faster than the direct implementation of the electric field-based soft-straightening algorithm. CONCLUSION: The fast algorithm for soft straightening of the colon has potential for use in computed tomographic colonography.

Algorithms↗

The active phase-related increase in corticosterone and aggression are linked.

Recently we demonstrated that corticosterone exerts an acute facilitatory effect on aggression in male rats. Corticosterone production reaches a maximum at the onset of the dark period, while male rats are more aggressive in the dark. Here we present evidence demonstrating that the corticosterone increase at the beginning of the dark period is causally linked to the increase in aggressiveness. We measured plasma corticosterone and quantified aggressive behaviour of male territorial rats at various time points of the day-night transition. Low aggression levels were observed in the full light period when plasma concentrations of corticosterone were low. An increase in plasma corticosterone occurred just prior to the dark phase, when aggressive responding was the highest. Aggressive behaviour remained high in the early dark period when corticosterone was still high. We found that blocking the high affinity mineralocorticoid receptor (MR) with spironolactone (5 or 10 mg/kg) during the early dark period dramatically and specifically reduced territorial aggression.

Aggression↗

Ultradian corticosterone rhythm and the propensity to behave aggressively in male rats.

Ultradian fluctuations in plasma glucocorticoids have been demonstrated in a variety of species including humans. The significance of such rhythms is poorly known, although disorganized ultradian glucocorticoid rhythms have been associated with behavioural disorders. Here we report that ultradian glucocorticoid rhythms may establish the propensity to behave aggressively in male rats. Male rats were significantly more aggressive in the increasing phase of their corticosterone fluctuation when confronting a male intruder than counterparts in the decreasing phase of their corticosterone fluctuations facing such opponents. Corticosterone fluctuations were mimicked by a combination of treatments with the corticosterone synthesis inhibitor metyrapone and corticosterone. Again, males with increased plasma corticosterone levels were more aggressive than counterparts with a decreased plasma corticosterone concentration. These data suggest that the behavioural response to an aggressive challenge may vary in the same animal across the day due to the pulsating nature of corticosterone secretion. Aggressive behaviour is also episodic in humans; moreover, intermittent explosive behaviour is recognized as a psychological disorder. It can be hypothesized that a temporal coincidence between the occurrence of a challenge and a surge in plasma corticosterone concentration may be one of the factors that promote episodic aggressive outbursts.

Activity Cycles↗

Housing conditions and the anxiolytic efficacy of buspirone: the relationship between main and side effects.

Serotonergic anxiolytics yield contradictory results both in the laboratory and clinically. In an attempt to investigate the cause of discrepancies, the anxiolytic effect of buspirone (0, 3 or 10 mg/kg, single treatment) was tested 1 h and 4 h after injection in rats in different housing conditions. At 1 h after drug administration, buspirone increased corticosterone production and decreased locomotor behaviour in both the elevated plus-maze and the social interaction tests. No anxiolytic-like effect was produced in either test. At 4 h after drug injection, no corticosterone or locomotor effects of buspirone were observed. In contrast, anxiolytic effects emerged in this phase. Open arm exploration and social investigation were increased in the plus-maze and social interaction test, respectively. In the plus-maze, the anxiolytic effect was significant in isolated animals only. In the social interaction test, the anxiolytic effect was stronger in isolated than in group-housed animals. When corticosterone secretion was inhibited by adrenalectomy, a full anxiolytic effect of buspirone was observed 1 h after drug administration. It appears that the side effects of buspirone have a shorter duration than the main anxiolytic effect. The buspirone-induced increase in corticosterone may have abolished the anxiolytic effects of the drug shortly after injection. Individual housing enhanced the anxiolytic efficacy of buspirone 4 h after administration.

Animals↗

Diuretic use: a risk for subclinical thiamine deficiency in elderly patients.

Long term diuretic therapy represents one central pharmacologic therapy of heart insufficiency and hypertension. Diuretics lead not only to an increased urinary excretion of electrolytes but also of water soluble vitamins. In this prospective study we evaluated the effect of hospitalization on the overall biochemical vitamin status in subjects older than 50 years (n=149, mean +/- SD age 70 +/- 10 years). Vitamin nutriture and other parameters were assessed at admission and discharge (duration of the hospitalization 19 +/- 1 day). Only vitamin B1 nutriture worsened during the hospitalization and in a multivariate procedure the only significant predictor of the change in the vitamin B1 nutriture was the use of diuretics during the hospitalization (F=4.06, p < 0.001). The changes in the ETK (erythrocyte transketolase activity in whole blood) and a-ETK (ETK activity coefficient) during the hospital stay correlated with the cumulative dosage of furosemide adjusted for the duration of the therapy (r = 0.36, p < 0.001 and r = - 0.28, p > 0.03). Our data suggest that hospitalized elderly are at increased risk for vitamin B1 deficiency especially when on a diuretic treatment. It is possible that a low dose thiamine supplementation my help to prevent the development of a subclinical wet-beriberi in older subjects on diuretics.

Aged↗

North Carolina macular dystrophy (MCDR1) locus: a fine resolution genetic map and haplotype analysis.

PURPOSE: We previously reported linkage of North Carolina macular dystrophy in a single isolated family to a broad region on chromosome 6q16. In order to refine the localization of the MCDR1 gene (North Carolina macular dystrophy), additional families with this disease and new markers were studied. METHODS: We ascertained 10 families with the North Carolina macular dystrophy phenotype (MCDR1). These families were of various ethnic and geographic origins such as Caucasian, Mayan Indian, African-American, French, British, German, and American of European decent. Two hundred thirty-two individuals in these families underwent comprehensive ophthalmic examinations and blood was collected for genotyping. One hundred seventeen were found to be affected. Linkage simulation studies were performed. Two-point linkage, haplotype analysis, and multipoint linkage was performed using VITESSE and FASTLINK. HOMOG was used to test for genetic heterogeneity. RESULTS: The clinical features were consistent with the diagnosis of North Carolina macular dystrophy in all families. Multipoint linkage analysis indicates that the MCDR1 gene is in the interval between D6D249 and D6S1671 with a maximum LOD score of 41.52. There was no evidence of genetic heterogeneity among the families studied. Families 765, 768, 772, 1193, and 1292 shared the same chromosomal haplotype in this region. CONCLUSIONS: This is the largest single data set of families with the MCDR1 phenotype. The single large family from North Carolina continues to be informative for the closest flanking markers and alone supports the minimal candidate region as suggested by previous studies. There remains no evidence of genetic heterogeneity in this disease. Most of the American families appear to have descended from the same ancestral mutation. The remaining families could each represent independent origins of the mutation in the MCDR1 gene.

Adolescent↗

Defeat is a major stressor in males while social instability is stressful mainly in females: towards the development of a social stress model in female rats.

Social stress models appear useful in elucidating the interrelationship between stress, mood disorders, and drug efficacy. However, reliable social stress models for females are virtually lacking. The aim of this study was to determine stress-related consequences of (a) defeat in aggressive encounters and (b) social instability, in male and female rats. Defeat in male and female subjects was induced by aggressive male residents and female residents made aggressive by surgery (mediobasal hypothalamic lesion [MBHL]), respectively. Aggressiveness of resident males and resident MBHL females was remarkably similar. Alternating isolation and mixed-sex crowding phases with membership rotation were used to induce social instability. Aggression was kept low in the latter paradigm by manipulating crowding group composition. Defeat stress reduced weight gain, and increased both adrenals and plasma corticosterone in males. Only adrenal weight was affected in females. Social instability reduced weight gain, and induced thymus involution, adrenal hypertrophy and elevated plasma corticosterone levels in females. Only weight gain and thymus weights were affected in males. It is concluded that defeat stresses males more than females, while social instability is more stressful for females than for males, if aggressive contacts are low. It is suggested that the social instability model is a good model of social stress in females.

Aggression↗

Virtual endoscopic environments in modern neurosurgical practice.

Modern radiographic techniques have allowed the creation of high-definition planar images that can provide important anatomical as well as physiological data. Planar imaging sets can be reformatted into three-dimensional (3-D) data sets that can then be manipulated to demonstrate important anatomical or gross pathological features. Three-dimensional data sets have been used with success in modern image-guided or frameless stereotactic surgery. Another potential application is so-called "virtual endoscopy" or "scopeless endoscopy," in which a 3-D anatomical data set is reformatted into a volume-rendered image that can then be viewed. By reformatting images in this way, a "surgeon's-eye" view can be obtained, which can aid in presurgical planning and diagnosis. The use of virtual endoscopy has the potential to increase our understanding of the appropriate anatomy and the anatomical relationships most apparent during neurosurgical approaches. In so doing, virtual endoscopy may serve as an important means of planning for therapeutic interventions. On the other hand, one must always be cognizant of the technical limitations of these studies regardless of the quality of the reconstructed images. Prospective, correlative, clinical studies in which the anatomical advantages of virtual-based endoscopy are evaluated in large cadaver or patient series must be performed. Until then, the only potential ways to compensate for errors that exist in the algorithms and reconstructions of 3-D endoscopic images are based on the surgeon's understanding of the clinical state of the patient and prior experience with the anatomy in the region of question.

Journal Article↗