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Biomedical subjects

I Fried

Publications and source records attributed to I Fried.

At least 55 records · Page 3Linked to original sources
PubMed1997

Assessing the impact of open-access HMOs on providers.

Open-access model HMOs, in which HMO members may seek specialty care without having to be referred by a primary care physician, have been hailed as the next major growth area for the managed care industry. This model is attractive to HMO members because it offers greater freedom in selecting and accessing providers. Payment mechanisms, though, tend to differ from those used by traditional gatekeeper model HMOs. The preferred method of payment in most open-access HMOs is to reimburse primary care physicians on a fee-for-service basis and capitate specialists. Open-access HMOs may lead to more restrictions for providers however, and their continued growth could lead to less desirable payment arrangements and weaker market positions. What types of payment and care delivery systems will ultimately result from open-access HMOs remain to be seen.

Capitation Fee↗
PubMed1996

Aberrant hippocampal mossy fiber sprouting correlates with greater NMDAR2 receptor staining.

This study determined in temporal lobe epilepsy patients and rats injected with intrahippocampal kainate (KA) whether fascia dentata molecular layer mossy fiber sprouting was associated with increases in NMDAR2 immunoreactivity (IR). Patients with hippocampal sclerosis (n = 11) were compared with those with temporal mass lesions (n = 7) and material obtained at autopsies (n = 4); and unilateral KA-injected rat hippocampi (n = 7) were compared with the contralateral saline-injected side and non-lesioned animals (n = 7; control). Hippocampi were studied for neo-Timm's stained mossy fiber sprouting and NMDAR2 IR. The staining was quantified as gray values (GV) using computer image analysis. Hippocampal sclerosis patients and KA-injected rats showed the greatest inner molecular layer (IML) mossy fiber sprouting and NMDAR2 staining. Compared with autopsies and patients with mass lesions, hippocampal sclerosis patients had greater IML neo-Timm's (p = 0.0018) and NMDAR2 staining (p = 0.0063). Similarly, compared with controls and saline-injected rats, KA-injected hippocampi showed greater IML mossy fiber sprouting and NMDAR2 IR (p = 0.0001). Furthermore, IML mossy fiber sprouting positively correlated with greater IML NMDAR2 staining in both human and experimental rat groups (p < 0.0099). These results support the hypothesis that in severely damaged hippocampi abnormal mossy fiber sprouting and concordant increases in IML NMDAR2 receptor staining may contribute or partially explain granule cell hyperexcitability and the pathophysiology of hippocampal epilepsy.

Adult↗
PubMed1996

Extracellular slow negative transient in the dentate gyrus of human epileptic hippocampus in vitro.

We investigated extracellular slow negative transient in dentate granule cells of human epileptic hippocampus. Hippocampal slices were prepared from brain specimens removed from 23 patients who underwent surgical treatment for medically intractable seizures. In 15 patients, hippocampi were sclerotic and the aberrant anatomical reorganization of dentate granule cell axons (mossy fibers) was detected. In eight patients, hippocampi were non-sclerotic and nominal reorganization was detected. Single perforant path stimulation evoked field responses in dentate granule cells in all 23 hippocampi. In sclerotic hippocampi, evoked field responses were followed by a slow onset extracellularly negative potential, which appeared gradually in the course of low frequency stimulation of the perforant path. Single action potentials could be recorded from negative potentials indicating that these potentials represented dentate granule cell depolarization. A low concentration of bicuculline methiodide (10 microM), a GABAA receptor antagonist, facilitated the appearance of negative potentials suggesting that a reduction in functional inhibition could unmask these potentials. The application of D-2 amino-5-phosphonovaleric acid blocked extracellular negative potentials, but initial perforant path responses were spared. This finding suggested that negative potentials were at least in part mediated by the N-methyl-D-aspartate receptor subtypes in their generation. In contrast, in non-sclerotic hippocampi with nominal "reorganization", no extracellular negative potentials were observed. The present study suggests that dentate granule cell excitability could be amplified when their reorganized axonal pathways were present in human sclerotic hippocampus as previously proposed in animal models of epilepsy.

2-Amino-5-phosphonovalerate↗
PubMed1996

Comparison of seizure related amino acid release in human epileptic hippocampus versus a chronic, kainate rat model of hippocampal epilepsy.

Recent microdialysis studies of excitatory and inhibitory amino acid release associated with paroxysmal hippocampal activity have found significant increases in the hippocampus of epileptic patients, but minimal or variable increases in animal models. One possible reason for the difference is that the animal models employed in these studies have not adequately reflected the pathophysiology of human epilepsy. The present study sought to verify the amino acid release reported in human epileptic hippocampus and then employs animal studies using a chronic rat model of epilepsy, in which rats exhibit spontaneous seizure activity 3 to 4 months after injection of kainic acid into the hippocampus. In agreement with earlier reports, we found increases in glutamate, aspartate and GABA during seizures in human hippocampus. In addition we found increases in taurine which have not previously been reported. The chronic rat model shows increases in the same amino acids as in the human epileptic hippocampus, both during spontaneous seizures and stimulation evoked after-discharges (ADs). In contrast, minimal increases are elicited by hippocampal stimulation in control (non-kainate injected) animals. These results correlate with the degree of mossy fiber reorganization found in the dentate gyrus of kainate rats or epileptic humans.

Amino Acids↗
PubMed1996

Intracranial electrode monitoring for seizure localization: indications, methods and the prevention of complications.

Surgery is a successful method of treatment for certain epilepsies. Patient evaluation is directed towards seizure classification and localization. In most cases patients are able to progress from a noninvasive evaluation utilizing extracranial electrodes directly to resective surgery. In a few complex situations patient evaluation requires the placement of intracranial electrodes for accurate localization of the epileptogenic focus. The placement of intracranial electrodes is a surgical procedure which carries significant risk. Meticulous multidisciplinary care is required to achieve a safe and successful surgical outcome. Astute nursing care is pivotal to the success of intracranial monitoring and essential to the prevention of complications.

Adult↗
PubMed1995

Human immunodeficiency virus 1 envelope proteins induce interleukin 1, tumor necrosis factor alpha, and nitric oxide in glial cultures derived from fetal, neonatal, and adult human brain.

Although microglia are the only cells found to be productively infected in the central nervous system of acquired immunodeficiency disease syndrome (AIDS) patients, there is extensive white and gray matter disease nonetheless. This neuropathogenesis is believed to be due to indirect mechanisms other than infection with human immunodeficiency virus 1 (HIV-1). Cytokines and toxic small molecules have been implicated in the clinical and histopathological findings in CNS AIDS. Previously, we have demonstrated in rodent glial cultures the presence of biologically active epitopes of gp120 and gp41 that are capable of inducing interleukin 1 and tumor necrosis factor alpha. In this study, we map the HIV-1 envelope epitopes that induce nitric oxide, inducible nitric oxide synthase, interleukin 1, and tumor necrosis factor alpha in human glial cultures. Epitopes in the carboxy terminus of gp120 and the amino terminus of gp41 induce these proinflammatory entities. In addition, we compare HIV-1 infection and pathology in glial cells derived from human brain taken at different states of maturation (fetal, neonatal, and adult brain) in an effort to address some of the clinical and histological differences seen in vivo. This study demonstrates that, in the absence of virus infection and even in the absence of distinct viral tropism, human glia respond like rodent glia to non-CD4-binding epitopes of gp120/gp41 with cytokine and nitric oxide production. Differences among fetal, neonatal, and adult glial cells' infectivity and cytokine production indicate that, in addition to functional differences of glia at different stages of development, cofactors in vitro and in vivo may also be critical in facilitating the biological responses of these cells to HIV-1.

Adolescent↗
PubMed1995

Magnetic resonance imaging and epilepsy: neurosurgical decision making.

Advances in magnetic resonance imaging (MRI) techniques have had an important impact on the decision-making process leading to surgical resection for chronic seizures. The MRI is now obtained relatively early in the work-up, and, when it shows abnormality, it assumes a crucial role in the detection of specific surgically remediable syndromes. These syndromes, when diagnosed by MR and other confirmatory studies such as electroencephalography (EEG), positron emission tomography (PET), magnetoencephalography (MEG), and neuropsychological testing, define the essential part of the surgical plan; that is, removal of the disease substrate. The availability of a host of MR techniques enable us to investigate epilepsy not only as a structural pathology but as physiological pathology reflected in abnormal blood flow, metabolism, and synaptic transmission. The mainstay of surgical treatment is the removal of the anatomic pathology, but other MR techniques may be helpful in the delineation of dual pathology in lesional cases, in appreciation of the full extent of microscopic pathology in developmental lesions, and in the imposition of restrictions on the resection based upon functional mapping. Finally, functional and anatomic maps obtained preoperatively can be related directly to the spatial coordinates of the exposed brain in the operating room using MRI-based frameless stereotactic methods. The final outcome, then, is the removal of the disease substrate without injury to adjacent, functionally salient cortical regions.

Brain Diseases↗
PubMed1995

The anatomy of epileptic auras: focal pathology and surgical outcome.

An aura is generally understood to be the beginning of a seizure. Yet, following successful surgery for intractable epilepsy, patients may have persistent auras even though they are otherwise seizure free. Ninety patients with intractable seizures and auras underwent resective surgery. Forty-three patients had hippocampal sclerosis and 47 had temporal or extratemporal lesions such as glial tumors or vascular malformations. The semiology of the auras was found to have value in localization but not lateralization of the pathology. Epigastric auras as well as gustatory and olfactory auras were significantly more frequent in patients with hippocampal sclerosis than in those with temporal or extratemporal lesions. Auras of vertigo or dizziness were most frequent in patients with extratemporal pathology. There was a significant difference between the pathology groups in the efficacy of resection in eliminating the auras. Of the patients with hippocampal sclerosis who were rendered seizure free, 18.9% had persistent auras, whereas only one (2.6%) of the patients with temporal or extratemporal lesions who were rendered seizure free had persistent auras. These findings suggest that for patients with hippocampal sclerosis an anatomical dissociation between seizure and aura may occur, whereas this dissociation is not present in patients with lesions. Patients suspected of having hippocampal sclerosis should be counseled preoperatively as to the significant likelihood of persistent auras even if seizures are successfully abolished.

Brain Diseases↗
PubMed1995

Functional MR and PET imaging of rolandic and visual cortices for neurosurgical planning.

Magnetic resonance (MR) imaging has recently been used to demonstrate physiological activation of the human brain. This development is of considerable interest to the neurosurgeon planning procedures near brain regions involving specific functions. In the present study, rolandic and visual cortices were imaged with a conventional 1.5-tesla clinical MR imager using a spoiled gradient-recalled acquisition in the steady state sequence. Two patients, one with a right frontal astrocytoma and the other with a left parietal meningioma, underwent MR imaging of rolandic cortex while performing a repetitive finger apposition task. Two patients with complex partial seizures referable to the temporal and occipital regions underwent MR imaging of visual cortex while exposed to repetitive photic stimulation (8.3 Hz). Significant signal intensity changes up to 15% between the activation and rest conditions were observed near the surgical targets at the expected anatomical location of the rolandic and visual cortices. In two of these cases activation measured by MR was compared and found similar to the activation measured at the same plane by H2(15)O positron emission tomography (PET). These results suggest that functional MR and PET techniques can be used to obtain preoperative brain mapping in individual patients considered for neurosurgical procedures.

Adult↗
PubMed1995

Mellansjö school-home. Psychopathic children admitted 1928-1940, their social adaptation over 30 years: a longitudinal prospective follow-up.

The school-home for "psychopathic" children, Mellansjö, was founded in 1928. The initiator was Alice Hellström, a teacher and physician. She was a child psychiatric pioneer in Sweden. She had no formal education in child and adolescent psychiatry but with support from Professor of Paediatrics Isaac Jundell she received education in pediatrics and from Professor of Psychiatry Bror Gadelius she was trained in psychiatry. Hellström made a study trip to Europe where she visited child psychiatry clinics. She visited Summerhill in England and professors Aichhorn and Lazar in Austria. When Hellström opened the school-home she had been influenced by a number of factors, including the ideas behind the Swedish Child Welfare Law of 1924. She was also influenced by curative education and the psychoanalysis theory. She regretted that she lacked psychoanalytical training, however. Hellström was responsible for Mellansjö during the period 1928-56. Total admissions of 387 boys and 235 girls were recorded. Hellström planned a prospective longitudinal study with support from Jundell. Her intention was to describe the outcome of the children. She collected background and follow-up data from 1928 to 1968. She was unable to complete her project before she died in 1981 at the age of 95. The study has been completed with a consistent examination and follow-up of the 242 children treated between 1928 and 1940. This can help us to understand child psychiatric patients from the 1930s and obtain knowledge about their outcome. Such knowledge is important for understanding how evolution in society can activate child and adolescent psychiatry and how new forms of treatment have something to provide beyond those that already exist. The follow-up showed that 55% of the boys and 89% of the girls had an outcome without criminality and/or alcoholism in spite of difficult adjustment problems during childhood and were considered to be "psychopaths" in the 30s. However, 45% of the boys developed criminality and/or alcoholism despite early discovery and treatment. This group of boys is characterized by heredity for mental insanity, criminality or alcoholism, low social class, word-blindness and pilfering--a special hypothesis put forward in accordance with Hellström's own intentions. "Children who have a heredity of addictions, criminality and mental disease, a vulnerability revealed in behaviour problems and learning difficulties in the absence of mental retardation run a greater risk of developing addictions and criminality."(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

Management of low-grade gliomas: results of resections without electrocorticography.

Low-grade gliomas associated with chronic seizures constitute a distinct clinicopathologic group of tumors that arise in young hosts, are based in gray matter of limbic or adjacent cortex, and usually have an indolent course. The most important factor in achieving long-term seizure control in these patients is complete removal of the lesion, to tumor-free margins. For low-grade gliomas in the temporal lobe, additional mesial temporal resection may be required, but there is no evidence that it need be based on ECoG. Using this procedure to define the epileptogenic zone for surgery may result in resections that are larger than necessary. The decision on extralesional hippocampal resection should be based on evaluation of the structural and functional status of the hippocampus by considering several variables, including seizure history, proximity of the tumor to the hippocampus, and the neuropsychologic profile of the patient, especially with regard to memory function.

Astrocytoma↗
PubMed1994

Callosal transmission time before and after partial commissurotomy.

Interhemispheric transmission time was measured in a patient, before and after partial commissurotomy sparing the splenium of the corpus callosum, using a simple reaction time paradigm with unimanual responses to lateralized flashes at 4 degrees and 8 degrees of eccentricity. Post-operative transfer time was longer than pre-operative transfer time at 8 degrees but not at 4 degrees of eccentricity. These data do not support the notion that the callosal transfer time is always faster through motor rather than visual fibers. They rather suggest that the callosal transfer time through visual fibers is longer than the callosal transfer time through motor fibers only for flashes at large eccentricities.

Adult↗
PubMed1994

Dynamic magnetic resonance imaging of human Rolandic cortex.

Rolandic cortex was imaged with magnetic resonance (MR) in nine subjects while performing a motor activation task. Imaging was performed by a volumetric, T2-weighted pulse sequence in a conventional 1.5 Tesla scanner during both resting conditions and volitional toe flexion and extension of the dominant foot. Significant changes in MR signal intensity of 7.8 +/- 2.3% (mean +/- s.e.m.) were observed in the medial Rolandic cortex contralateral to the active foot. Changes were maximal in the vicinity of the central sulcus, but were also identified anteroposteriorly, across successive coronal planes. No significant changes were found in the ipsilateral Rolandic cortex or in other brain structures. Volumetric functional MRI strategies may provide an important non-invasive tool for assessment of cortical motor function.

Adolescent↗
PubMed1994

Direct measurement of extracellular lactate in the human hippocampus during spontaneous seizures.

The effect of clinical, spontaneous-onset seizures on extracellular fluid lactate was investigated by the method of lactography, the in vivo on-line measurement of lactate levels using microdialysis. Studies of experimental animals have suggested that generation of extracellular lactate as measured by microdialysis is an index of local glucose utilization and is dependent on the activity of neurons under physiological conditions. Patients with medically refractory complex partial epilepsy underwent stereotactic implantation of combination depth electrode/microdialysis probes into both hippocampi for 7-16 days. During spontaneous complex partial seizures with secondary generalization, extracellular lactate levels rose by 91 +/- 32%. Moreover, this increase persisted for 60-90 min. During a unilateral hippocampal seizure that did not propagate to the contralateral hippocampus, the increase in lactate content was restricted to the side of seizure activity. Between seizures, extracellular lactate levels correlated with the frequency of interictal spikes. In summary, these data suggest that brief clinical seizures increase nonoxidative glucose metabolism significantly as measured by the generation of extracellular lactate. Furthermore, the increase in extracellular lactate levels is limited to the site of seizure activity. Lactate is transported extracellularly via a lactate/proton cotransporter, therefore, the rise in extracellular lactate level may mediate the drop in pH0 associated with seizure activity. As acidification of the extracellular compartment has an inhibitory effect on neuronal excitability, the rise in extracellular lactate content may be a mechanism of seizure arrest and postictal refractoriness. Moreover, extracellular lactate may also mediate the decreased seizure susceptibility associated with frequent interictal spikes.

Adolescent↗
PubMed1994

Limbic and neocortical gliomas associated with intractable seizures: a distinct clinicopathological group.

The authors studied 65 patients with intractable seizures and glial tumors who were treated between 1978 and 1991. Most of the tumors were in the temporal (63%) or occipital lobe (18%) and were commonly found in limbic or perilimbic neocortical locations. The majority of these gliomas (83%) involved the gray matter of allocortex, neocortex, or transitional cortex. These tumors spanned a wide range of glial differentiation: Most (61%) were low-grade astrocytomas, but 17% were histologically malignant. However, their biological behavior was strikingly indolent, as suggested by a stable clinical history during many years of chronic seizures (mean, 15 yr). The median follow-up time since the onset of symptoms in these patients was 17.2 years, and only one patient in the entire series died from the tumor. The mainstay of the surgical treatment was resection of the gliomas to histologically confirmed, tumor-free margins. The resection was not guided by intraoperative electrocorticography. Of the 60 patients who had a postoperative follow-up of more than 1 year, 82% were seizure free. Of the 31 patients who had auras with their seizures, 87% did not retain their auras postoperatively. Of the patients who were rendered seizure free, only one patient continued to have auras. Failure in seizure control was associated with an incomplete resection of the lesion. In patients with temporal lobe tumors, seizure outcome was not significantly related to the extent of medial temporal resection. It is suggested that limbic and perilimbic gliomas associated with intractable seizures constitute a distinct clinicopathologic group of glial tumors that involve the gray matter, arise in a young host, and exhibit stable biological behavior over many years. Surgical treatment that includes complete resection of these tumors can achieve excellent seizure control.

Adolescent↗
PubMed1993

Low-grade astrocytomas may arise from different astrocyte lineages.

The management of low-grade astrocytomas remains a challenge. Although the majority of these tumors have common histological features, they may have very different clinical manifestations and rates of proliferation. Because low-grade astrocytomas are composed of relatively well-differentiated neoplastic cells that closely resemble the astrocytic phenotype, it is possible that some of these lesions express antigens that characterize astrocyte lineages. The authors performed an immunohistochemical analysis of 20 low-grade astrocytomas with A2B5, a monoclonal antibody to a ganglioside found in early postnatal Type 2 (fibrillary) astrocytes, but absent in Type 1 (protoplasmic) astrocytes, and anti-glial fibrillary acidic protein to determine whether the expression of these antigens could be used to determine the histogenesis of these tumors. These findings were compared with the clinical and imaging features of these tumors. The percentages of cells positive for A2B5 and glial fibrillary acidic protein was strongly correlated with the location of the tumor within the cortex or white matter and with the length of preoperative symptoms. Tumors based in the cortex contained significantly fewer A2B5-positive and glial fibrillary acidic protein-positive cells than white matter tumors. In addition, lesions that caused a relatively short period of preoperative symptoms (< 1 year) had significantly more A2B5-positive and glial fibrillary acidic protein-positive cells than lesions responsible for a long preoperative history (mean, 12.9 years). These findings suggest that slow-growing, cortically based low-grade astrocytomas have a phenotype consistent with the Type 1 (protoplasmic) astrocyte lineage, while white matter low-grade astrocytomas express antigens consistent with the Type 2 (fibrillary) astrocyte lineage.

Adolescent↗