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Biomedical subjects

L Steiner

Publications and source records attributed to L Steiner.

At least 19 recordsLinked to original sources

[Lipomatous hypertrophy of the cardiac interatrial septum].

Lipomatous hypertrophy of the interatrial septum (LHIS) is a rare lesion of unknown origin usually diagnosed as an incidental finding during autopsy. It can be associated with supraventricular arrhythmias, venous return obstruction and sudden cardiac death. Five necropsy cases (4 females, 1 male) of LHIS were encountered during the last 31 years; only one case from this series was diagnosed ante mortem. The patients' mean age was 68 years; their mean BMI was 28.4. The mean size of the lesion was 31 mm. In three patients the LHIS was asymptomatic, two patients experienced relapsing multifocal atrial tachycardia and sick sinus syndrome, respectively. Histologically, all cases consisted of a mixture of mature and brown adipose tissue with foci of cardiomyocytes. For a pathologist the knowledge of LHIS is important because of an increasing possibility of its ante mortem diagnosis by imaging methods with a following endomyocardial biopsy, and also because it may appear as a cause of sudden cardiac death.

Adipose Tissue↗

ICM+: software for on-line analysis of bedside monitoring data after severe head trauma.

ICM software was developed in 1986 in Warsaw, Poland and has been in use at the University of Cambridge Neurocritical Care Unit for 10 years collecting data from bed-side monitors in nearly 600 severely head injured patients and calculating secondary indices describing cerebral autoregulation and pressure-volume compensation. The new software ICM+ includes a much extended calculation engine that allows easy configuration and on-line trending of complex parameters. The program records raw signals, and calculates time trends of summary parameters. Configuration and analysis utilises arithmetic expressions of signal processing functions to calculate various statistical properties for each signal, frequency spectrums and derivatives, as well as correlations/cross-correlations between signals. The software allows configuration of several levels of analysis before calculating the final time trends. The final data are displayed in a variety of ways including simple time trends, as well as time window based histograms, cross histograms, correlations etc. All this allows complex information coming off the bed-side monitors to be summarized in a concise fashion and presented to medical and nursing staff in a simple way that alerts them to the development of various pathological processes. The system provides a universal tool for clinical and academic purposes. Its flexibility and advanced signal processing is specialized for the needs of multidisciplinary brain monitoring.

Craniocerebral Trauma↗

Concept of "true ICP" in monitoring and prognostication in head trauma.

OBJECTIVE: To propose a new coefficient, which contains information about both the absolute ICP and the position of the 'working point' on the pressure-volume curve. METHOD: ICP was monitored continuously in 187 sedated and ventilated patients. The RAP coefficient was calculated as the running (3 minutes) correlation coefficient between slow changes in pulse amplitude and mean ICP. RAP has value 0 on the flat part of the Pressure-Volume Curve and +1 on the ascending exponential part. Then RAP decreases to zero or becomes negative when ICP increases further and affects cerebrovascular pressure-reactivity (which flattens the pressure-volume curve). Variable tICP = ICP* (1 - RAP) has been called 'trueICP'. It magnifies the critical values of ICP when cerebrovascular reactivity is exhausted and dampens those states where absolute ICP is elevated but vascular reactivity is not affected. RESULTS: Both Mean ICP and RAP were independently correlated with outcome (ANOVA:ICP-GOS: F = 22; p < 0.00001, RAP-GOS: F = 9; p < 0.001). 'TrueICP' had stronger association with outcome: F = 28; p < 0.000001. Mortality in those patients having 'trueICP' above the threshold of 19 mm Hg was above 80%, while the mortality in those having cICP below 19 mm Hg was only 20% (F = 80; p < 10(-8)). 'TrueICP' was also suitable for continuous monitoring: sustained rise in tICP above 19 mm Hg was strongly associated with fatal complications. CONCLUSION: The proposed variable is a powerful predictor of fatal outcome following head injury. It is sensitive to both the rising absolute ICP and the critical loss of cerebrovascular regulation.

Adolescent↗

Multi-locus interactions predict risk for post-PTCA restenosis: an approach to the genetic analysis of common complex disease.

The complexity of recognizing the potential contribution of a number of possible predictors of complex disorders is increasingly challenging with the application of large-scale single nucleotide polymorphism (SNP) typing. In the search for putative genetic factors predisposing to coronary artery restenosis following balloon angioplasty, we determined genotypes for 94 SNPs representing 62 candidate genes, in a prospectively assembled cohort of 342 cases and 437 controls. Using a customized coupled-logistic regression procedure accounting for both additive and interactive effects, we identified seven SNPs in seven genes that, together, showed a statistically significant association with restenosis incidence (P <0.0001), accounting for 11.6% of overall variance observed. Among them are candidate genes for cardiovascular pathophysiology (apolipoprotein-species and NOS), inflammatory response (TNF receptor and CD14), and cell-cycle control (p53 and p53-associated protein). Our results emphasize the need to account for complex multi-gene influences and interactions when assessing the molecular pathology of multifactorial medical entities.

Angioplasty, Balloon, Coronary↗

Radiosurgery-induced microvascular alterations precede necrosis of the brain neuropil.

OBJECTIVE: Radiosurgery is used as a therapeutic modality for a wide range of cerebral disorders. It is important to understand the underlying causes of deleterious side effects that may accompany gamma-irradiation of brain tissue. In this study, structural alterations in rat cerebral vessels subjected to gamma knife irradiation in vivo were examined, for elucidation of their potential role in necrosis formation. METHODS: A maximal center dose of 75 Gy was delivered to the rat parietal cortex with a 4-mm collimator, and changes occurring before necrosis formation were assessed 3.5 months after irradiation. Transmission electron microscopy, using horseradish peroxidase as a tracer, and scanning electron microscopy with vascular casting were performed. RESULTS: The capillary network in the irradiated area exhibited thickening and vacuolation of the basement membrane. The capillary density in the irradiated area was lower and the average capillary diameter was larger, compared with the nonirradiated side. These results indicate that substantial changes in the neuropil do not occur 2 weeks before the time of definite necrosis formation, whereas changes in the basement membrane are prominent. CONCLUSION: The necrotic response to intermediate doses of focused-beam irradiation appears after a considerable latency period and then progresses rapidly. This contrasts with previously reported responses to fractionated whole-brain irradiation, in which damage occurs slowly and gradually. Alterations in the microvascular basement membrane precede overt cellular changes in neuronal and vascular cells and provide an early index of cerebrovascular dysfunction in regions destined to undergo necrosis.

Animals↗

Strategies for disseminating evidence-based practices to staff who treat people with serious mental illness.

Evidence-based practices have not been widely implemented in real-world treatment settings for several reasons, including existing state laws, administrative policies, funding priorities, advocates' concerns, and program staffing. Dissemination strategies focus largely on program staffing and the question of why treatment teams that are responsible for assisting people with serious mental illness fail to use evidence-based practices. In a review of the research literature, two barriers to staff dissemination emerge: individual service providers lack the necessary knowledge and skills to assimilate these practices, and certain organizational dynamics undermine the treatment teams' ability to implement and maintain innovative approaches. Three sets of strategies are useful for overcoming these barriers and fostering dissemination: packaging evidence-based practices so that specific interventions are more accessible and user-friendly to service providers; educating providers about relevant knowledge and skills; and addressing the organizational dynamics of the team to facilitate the implementation of innovations. Research on dissemination is relatively new and is less well developed than the clinical and services research enterprise that has led to evidence-based practices. Implications for future studies are discussed.

Chronic Disease↗

Anticonvulsant effects of gamma surgery in a model of chronic spontaneous limbic epilepsy in rats.

OBJECT: The management of intractable epilepsy remains a challenge, despite advances in its surgical and nonsurgical treatment. The identification of low-risk, low-cost therapeutic strategies that lead to improved outcome is therefore an important ongoing goal of basic and clinical research. Single-dose focal ionizing beam radiation delivered at necrosis-inducing and subnecrotic levels was investigated for its effects on seizure activity by using an established model of chronic recurrent spontaneous limbic seizures in rats. METHODS: A single 90-minute period of repetitive electrical stimulation (inducing stimulus) of the hippocampus in rats elicited a single episode of status epilepticus, followed by a 2- to 4-week seizure-free period. Spontaneous recurrent seizures developed subsequently and persisted for the duration of monitoring (2-10 months). Simultaneous computerized electroencephalography and video recording were used to monitor the animals. After the establishment of spontaneous recurrent seizures, bilateral radiation centered in the ventral hippocampal formation was administered with the Leksell gamma knife, aided by a stereotactic device custom made for small animals. A center dose of 10, 20, or 40 Gy was administered using a 4-mm collimator. Control animals were subjected to the same seizure-inducing stimulus but underwent a sham treatment instead of gamma irradiation. In a second experiment, the authors examined the effects of gamma irradiation on the proclivity of hippocampal neurons to display epileptiform discharges. Naive animals were irradiated with a single 40-Gy dose, as already described. Slices of the hippocampus were prepared from animals killed between 1 and 178 days postirradiation. Sensitivity to penicillin-induced epileptiform spiking was examined in vitro in slices prepared from control and irradiated rat brains. CONCLUSIONS: In the first experiment, single doses of 20 or 40 Gy (but not 10 Gy) reduced substantially, and in some cases eliminated, behaviorally and electrographically recognized seizures. Significant reductions in both the frequency and duration of spontaneous seizures were observed during a follow-up period of up to 10 months postradiation. Histological examination of the targeted region did not reveal signs of necrosis. These findings indicate that single-dose focal ionizing beam irradiation at subnecrotic dosages reduces or eliminates repetitive spontaneous seizures in a rat model of temporal lobe epilepsy. In the second experiment, synaptically driven neuronal firing was shown to be intact in hippocampal neurons subjected to 40-Gy doses. However, the susceptibility to penicillin-induced epileptiform activity was reduced in the brain slices of animals receiving 40-Gy doses, compared with those from control rats that were not irradiated. The results provide rational support for the utility of subnecrotic gamma irradiation as a therapeutic strategy for treating epilepsy. These findings also provide evidence that a functional increase in the seizure threshold of hippocampal neurons contributes to the anticonvulsant influence of subnecrotic gamma irradiation.

Animals↗

Gamma surgery for hemangiopericytomas.

A retrospective analysis of a consecutive series of 12 patients with 15 intracranial hemangiopericytomas treated at the University of Virginia using Gamma surgery is presented. Clinical and radiographic follow up of 3 to 56 months is available for 10 patients with 12 tumors. There was one tumor present at the time of initial Gamma surgery in each patient. Two new tumors occurred in patients previously treated. Nine of the tumors decreased in volume and three remained stable. Four of the nine tumors that shrank later progressed at an average of 22 months after treatment. Of the tumors that decreased in volume and have not progressed, the response has been for an average of 11 months. The follow-up for two tumors that remained unchanged was 10 and 34 months (average 22 months). A third tumor was unchanged at 42 months but the patient died of new disease adjacent to the treated area in the anterior skull base. There were no complications and the quality of life following the procedure was maintained or improved in every case. Gamma surgery is effective in palliating the patients by decreasing tumor volume and delaying recurrence.

Adult↗

Gamma surgery for vestibular schwannoma.

OBJECT: The goal of this study was to assess the results of gamma surgery (GS) for vestibular schwannoma (VS) in 200 cases treated over the last 10 years and to review the role of this neurosurgical procedure in the management of VS. METHODS: Follow-up reviews ranging from 1 to 10 years were available in 153 of these patients. Follow-up images in these cases were analyzed using computer software that we developed to obtain volume measurements for the tumors, and the clinical condition of the patients was assessed using questionnaires. Gamma surgery was the primary treatment modality in 96 cases and followed microsurgery in 57 cases. Tumors ranged in volume from 0.02 to 18.3 cm(3). In the group in which GS was the primary treatment, a decrease in volume was observed in 78 cases (81%), no change in 12 (12%), and an increase in volume in six cases (6%). The decrease was more than 75% in seven cases. In the group treated following microsurgery, a decrease in volume was observed in 37 cases (65%), no change in 14 (25%), and an increase in volume in six (11%). The decrease was more than 75% in eight cases. Five patients experienced trigeminal dysfunction; in three cases this was transient and in the other two it was persistent, although there has been improvement. Three patients had facial paresis (in one case this was transient, lasting 6 weeks; in one case there was 80% recovery at 18 months posttreatment; and in one case surgery was performed after the onset of facial paresis for presumed increase in tumor size). Over a 6-year period, hearing deteriorated in 60% of the patients. Three patients showed an improvement in hearing. No hearing deterioration was observed during the first 2 years of follow-up review. CONCLUSIONS: Gamma surgery should be used to treat postoperative residual tumors as well as tumors in patients with medical conditions that preclude surgery. Microsurgery should be performed whenever a surgeon is confident of extirpating the tumor with a risk-benefit ratio superior to that presented in this study.

Adolescent↗

Gamma surgery for intracranial metastases from renal cell carcinoma.

OBJECT: The goal of this study was to evaluate the effectiveness and limitations of gamma surgery (GS) in the treatment of renal cell carcinoma that has metastasized to the brain. METHODS: The authors performed a retrospective analysis of a consecutive series of 21 patients with 37 metastatic brain deposits from renal cell carcinoma who were treated with GS at the University of Virginia from 1990 to 1999. Clinical data were available in all patients. No patient died of progression of intracranial disease or deteriorated neurologically following GS. Eight patients clinically improved. Follow-up imaging studies were available for 23 tumors in 12 patients. Nine patients did not undergo follow-up imaging. One patient lived 17 months and succumbed to systemic disease: no brain imaging was performed in this case. Another patient refused further imaging and lived 7 months. Seven patients lived up to 4 months after the procedure; however, their physicians did not require these patients to undergo follow-up imaging examinations because of their general conditions-all had systemic progression of disease. Of the 23 tumors that were observed posttreatment, one remained unchanged in volume, 16 decreased in volume, and six disappeared. No tumor progressed at any time, and there were no radiation-induced changes on follow-up imaging an average of 21 months after GS (range 3-63 months). CONCLUSIONS: Gamma surgery provides an alternative to surgical resection of metastatic brain deposits from renal cell carcinoma. Neurological side effects were seen in only one case; freedom from progression of disease was achieved in all cases.

Adult↗

Gamma surgery for vein of Galen malformations.

OBJECT: The goal of this study was to evaluate the results of gamma surgery in nine patients treated for vein of Galen malformations (VGMs). METHODS: A consecutive series of nine VGMs in eight children aged 4 to 14 years and in one adult were treated with gamma surgery. Six of the patients were male, including the adult, and three were female. Among these patients there were three Yasargil Type I, one Type II, two Type III, and three Type IV malformations. Previous embolization had failed in four cases. Three VGMs were treated with gamma surgery twice. An additional patient with a Type III VGM underwent stereotactic angiography in preparation for gamma surgery but was judged to be suitable for direct embolization. Follow-up angiograms were obtained in eight of the VGMs treated. Four no longer filled; one has probably been obliterated, but this cannot be confirmed because the patient refused to undergo final angiography; one patient has residual fistulas not included in the initial treatment field, which were retreated recently; and two other patients have marked reduction of flow through their VGMs. CONCLUSIONS: Gamma surgery is a viable option in the treatment of VGMs in clinically stable patients. Combined endovascular therapy and gamma surgery is of benefit in complex malformations.

Adolescent↗

Gamma knife surgery for previously irradiated arteriovenous malformations.

OBJECTIVE: The goal was to report the treatment results after a second gamma knife treatment and to compare them with the results obtained after a first gamma knife treatment, as well as to investigate whether the models to predict the results after a first treatment are also applicable after gamma knife treatment of previously irradiated arteriovenous malformations. METHODS: The number of complications and the posttreatment hemorrhage rate were recorded for 112 patients in the study, and the number of obliterations was recorded for the 101 patients for whom conclusive angiograms were obtained. The results were compared with the expected results after a first gamma knife treatment. RESULTS: The observed number of obliterations was 62, which is not significantly different from the predicted number of 65. There were 14 observed and 5 predicted complications. When the risk from the preceding radiation treatment was added, the observed number of complications was similar to the predicted number. Six hemorrhages were observed after the second treatment. Of the 5 patients with unchanged arteriovenous malformation size after both the first and second treatments, 2 experienced hemorrhages after the second treatment, compared with none among the 81 patients for whom the malformation was obliterated or significantly decreased in size after the second treatment. CONCLUSIONS: The obliteration rate after gamma knife surgery for previously irradiated arteriovenous malformations is similar to that after primary gamma knife treatment. The complication rate increases with the amount of radiation previously given. The incidence of posttreatment hemorrhages is lower in the latency period if the malformation is affected by the radiation.

Adolescent↗

Radiosurgery for cavernous malformations.

OBJECT: The authors examined 22 patients with cavernous malformations (CMs) who had undergone gamma knife radiosurgery (GKRS) to assess the value of this procedure in treating these lesions. METHODS: At the Karolinska Hospital, GKRS was used to treat 23 patients with CMs during the period of 1985 through 1996. One of the patients was lost to follow up and the treatment results of the 22 remaining patients were analyzed. In the first half of the series, the CMs were treated with high doses of radiation (> 15-Gy dose to the periphery); in the second half of the series, lower doses were used. Nine of the 22 patients suffered a post-GKRS hemorrhage and six developed a radiation-induced complication (two of these patients experienced both). Some time after GKRS was performed, surgical removal of the CM had to be undertaken in four patients because of hemorrhage and in two patients because of radiation-induced complications. Four of the nine patients who experienced no post-GKRS hemorrhage or radiation-induced complication were treated before 1990; recent magnetic resonance imaging revealed a decrease in the size of the CM in three of these individuals and no size change in the other. The annual post-GKRS hemorrhage rate was 8% in this group. There was a trend in the hemorrhage rate to decrease 4 years postsurgery. There was also a trend for higher radiation doses administered to the periphery of the lesion to result in a lower risk of posttreatment hemorrhage. However, it could not be concluded whether GKRS affects the natural course of a CM. The incidence of radiation-induced complications was approximately seven times higher than that expected if the same number of patients had been treated by GKRS with the same radiation dose distributions for arteriovenous malformations instead of CMs. CONCLUSIONS: The high incidence of radiation-induced complications does not seem to justify the limited protection the treatment may afford in only exceptional cases. A prospective randomized study is needed before the role of radiosurgery in the management of these lesions can be defined. Until such a study has proved differently, a caveat must be raised for the treatment of CM with GKRS.

Cavernous Sinus↗

Endothelial cells as cytotoxic effector cells: cytokine-activated rat islet endothelial cells lyse syngeneic islet cells via nitric oxide.

In vivo, each beta cell is located in proximity to at least one capillary islet endothelial cell. Rat aorta and islet endothelial cells can be activated in vitro to express inducible nitric oxide synthase by a cytokine mixture of tumour necrosis factor-alpha, gamma-interferon, and interleukin-1 beta and to produce high concentrations of nitric oxide. We have performed co-culture experiments with rat islet endothelial cells together with isolated syngeneic islet cells at low target:effector ratios with or without previous cytokine challenge of endothelial cultures. Co-cultures were always free of exogenous cytokines, which were removed prior to addition of islet cells. We found that pre-activated, in contrast to resident islet endothelial cells, at a target:effector ratio as low as 1:1 almost completely lysed syngeneic beta and non-beta cells with 24 h of co-culture. Lysis by pre-activated islet endothelial cells was found to be preceded by DNA damage found in 46% of islet cells after 8 h of co-culture with pre-activated vs 7% with resting islet endothelial cells. Lysis was blocked to control levels in the presence of the nitric oxide synthase inhibitor NG-methyl-L-arginine. With the results presented here, we demonstrate for the first time, that activated endothelial lining cells can express effector cell activity and thus can contribute to local tissue destruction, especially in organs that are densely capillarized such as pancreatic islets.

Animals↗

Calf health in cow-calf herds in Switzerland.

In 1993, an observational study was initiated to provide general information on animal health in extensive beef farms, to estimate disease frequency and the economic impact of calf diseases and to identify risk factors related to health and weight gain. The longitudinal study was conducted from fall 1993 until winter 94/95 and included 100 farms in western Switzerland. The basic concept was to follow one generation of calves on these farms and record all events concerning animal health from birth to weaning. The study population included 1270 calves (most were Angus crossbreds). Farm-management data were collected with a questionnaire conducted on the farm. Birth and weaning weights were obtained from the beef cattle breeding association. Clinical diagnoses and treatment costs were provided by the farm veterinarians. Two thirds of the dead calves were submitted to a complete postmortem examination. Fifty-three percent of the farms in the study were primary type income farms while 47% were secondary type income farms. Thirty-eight percent of the farms were situated in the lower areas of Switzerland, 14% in the prealpine foothills, the remaining 48% were located in mountain areas. Preweaning calf mortality was 5%. The main causes of calf deaths were respiratory diseases and digestive disorders. Twenty-two percent of the calves were treated at least once by a veterinarian; 36% of the treatments administered by the veterinarian were applied because of diarrhea, 27% because of respiratory diseases. Disease incidence was highest during the months of November, December and January. The association of disease and potential farm-level risk factors was analysed using chi 2-statistics and multivariable regression methods including generalized estimating equations to adjusted for herd effects. Specific risk factors for disease were not identified. Treatment for disease was not associated with 250-day standardized weight gain.

Aging↗