[Therapeutic approach to motor fluctuation in patients with Parkinson disease].
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Antiparkinson Agents↗
Biomedical subjects
M Schwartz
Publications and source records attributed to M Schwartz.
Stereotactic radiosurgery: comparing different technologies.
Radiosurgery can be defined as 3-dimensional stereotactic irradiation of small intracranial targets by various radiation techniques. The goal is to deliver, with great accuracy, a large, single fraction dose to a small intracranial target, while minimizing the absorbed dose in the surrounding tissue. This article describes certain technical aspects of radiosurgery and compares the different methods of performing such treatment. The 2 most frequently used types of devices for radiosurgery are units with multiple cobalt sources (e.g., the Gamma Knife) and those based on a linear accelerator. In the former, highly collimated beams of radiation from the cobalt sources intersect at the target. In the latter, the source of a highly collimated beam of high-energy photons directed at the target turns through an arc or set of arcs. The accuracy of target localization, the steepness of fall-off of the radiation dose outside the target and the ability to irradiate an irregularly shaped target are all comparable for these 2 types of devices, despite claims to the contrary.
Humans↗
Effect of melittin on PD, resistance and short-circuit current in the frog gastric mucosa.
In an in-vitro preparation of gastric mucosae of Rana pipiens, the effect of adding melittin to a concentration of 5x10-6 M in the secretory solution on the transepithelial potential difference (PD), resistance (R) and short-circuit current (Isc) was studied. In 20 min, melittin decreased the PD by 9.3 mV and R by 148 ohm cm2. These changes can be explained by a decrease in the resistance, RP, of the paracellular pathway. To determine whether specific-ion pathways were responsible for the decrease in R, the effect of melittin on the partial conductances of Cl-, K+ and Na+ was also studied using the ion substitution method. Melittin decreased the PD response to changes in nutrient Na+, K+ and Cl- and the PD response to changes in secretory Cl-, but did not affect PD responses to changes in secretory Na+ or K+. Therefore, melittin decreased the nutrient membrane partial conductances of Cl-, K+ and Na+ and secretory membrane partial conductance of Cl-, without affecting the secretory partial conductances of Na+ or K+. Initially, melittin increased Isc in regular and Cl--free but not in Na+-free solutions. There was a delayed decrease in Isc. The results indicate that melittin decreases RP, increases the Na+ conductance of the secretory membrane and inhibits, eventually, the Na+/K+-ATPase pump.
Animals↗
[Adrenogenital syndrome--molecular biology and prenatal diagnosis].
Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive disorders affecting the synthesis of adrenal corticosteroids. CAH is caused by a functional defect in any one of five enzymatic steps required for the biosynthesis of cortisol. Deficiency of 21-hydroxylase is the most frequent of these disorders, accounting for approximately 95% of all CAH cases. 21-hydroxylase deficiency is due to mutations in the gene CYP21 encoding the enzyme. Using molecular biology techniques mutations in the involved families can be characterized, thereby allowing prenatal diagnosis in following pregnancies. Likewise fast and reliable carrier diagnosis can be offered to relatives of the patient.
Adrenal Hyperplasia, Congenital↗
Elevation of intraocular glutamate levels in rats with partial lesion of the optic nerve.
BACKGROUND: Acute partial lesion of the rat optic nerve, although not a model for glaucoma, mimics some of the features of the disease. OBJECTIVE: To learn whether degeneration of rat optic nerve fibers and death of their retinal ganglion cells induced by an acute partial lesion are associated with elevated levels of glutamate, known to occur in the eyes of humans and monkeys with glaucoma. MATERIALS AND METHODS: Rat optic nerve was subjected to a partial crush injury. Aqueous humor samples were aspirated from the anterior and posterior aqueous chambers at specified times and their amino acid contents were determined by means of high-performance liquid chromatography. RESULTS: Three and 7 days after injury, intraocular glutamate and aspartate levels were found to be significantly higher than in normal or sham-operated-on eyes, and returned to normal by day 14. CONCLUSIONS: Degeneration of the optic nerve, induced by a mechanical injury of the axons, leads to intraocular elevation of glutamate and aspartate levels. These results illustrate that the model of the partial optic nerve lesion exhibits another feature typical of a long-term optic neuropathy, such as glaucoma.
Animals↗
Electrical properties of glucose-sensitive hydrogels: swelling and conductivity relationships.
The electrical characteristics of a glucose-sensitive polymeric hydrogel have been studied. The hydrogel matrices were prepared by radical polymerization of solutions containing 2-hydroxyethyl methacrylate, N,N-dimethyl aminoethyl methacrylate, tetraethylene glycol dimethacrylate, ethylene glycol, water, and glucose oxidase. The hydrogels displayed faster and higher swelling rates for lower levels of a crosslinking agent. Electrical conductivity was found to be a sensitive measurement of the state of the swelling. A simple model that relates hydrogel swelling and conductivity has been proposed.
Electric Conductivity↗
Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): review and report of thirty novel mutations.
Glutaric acidemia type I (GA1) is caused by mutations in the gene encoding the enzyme glutaryl-CoA dehydrogenase (GCD). Sixty-three pathogenic mutations identified by several laboratories are presented, 30 of them for the first time, together with data on expression in Escherichia coli and relationship to the clinical and biochemical phenotype. In brief, many GCD mutations cause GA1, but none is common. There is little if any relationship between genotype and clinical phenotype, but some mutations, even when heterozygous, seem especially common in patients with normal or only minimally elevated urine glutaric acid.
Amino Acid Metabolism, Inborn Errors↗
Differential effects of central and peripheral nerves on macrophages and microglia.
The poor ability of injured central nervous system (CNS) axons to regenerate has been correlated, at least partially, with a limited and suppressed postinjury inflammatory response. A key cell type in the inflammatory process is the macrophage, which can respond in various ways, depending on the conditions of stimulation. The aim of this study is to compare the activities of macrophages or microglia when encountering CNS and peripheral nervous systems (PNS), on the assumption that nerve-related differences in the inflammatory response may have implications for tissue repair and thus for nerve regeneration. Phagocytic activity of macrophages or of isolated brain-derived microglia was enhanced upon their exposure to sciatic (PNS) nerve segments, but inhibited by exposure to optic (CNS) nerve segments. Similarly, nitric oxide production by macrophages or microglia was induced by sciatic nerve segments but not by optic nerve segments. The previously demonstrated presence of a resident inhibitory activity in CNS nerve, could account, at least in part, for the inhibited phagocytic activity of blood-borne macrophages in CNS nerve as well as of microglia resident in the brain. It seems that the CNS microglia are reversibly immunosuppressed by the CNS environment, at least with respect to the activities examined here. It also appears from this study that the weak induction of early healing-related activities of macrophages/microglia in the environment of CNS might explain the subsequent failure of this environment to acquire growth-supportive properties in temporal and spatial synchrony with the needs of regrowing axons.
Animals↗
Degeneration of spared axons following partial white matter lesion: implications for optic nerve neuropathies.
Neuroprotective therapy is a relatively new development in the approach to the treatment of acute and chronic brain damage. Though initially viewed in the framework of acute CNS injuries, the concept was recently extended to include chronic injuries, in which at any given time there are some neurons in an acute phase of degeneration coexisting with others that are healthy, marginally damaged, or dead. The healthy neurons and those that are only marginally damaged are the potential targets for neuroprotection. For the development of neuroprotective therapies, it is essential to employ an animal model in which the damage resulting from secondary degeneration can be quantitatively distinguished from primary degeneration. This is of particular relevance when the site of the damage is in the white matter (nerve fibers) rather than in the gray matter (cell bodies). In the present work we reexamine the concepts of secondary degeneration and neuroprotection in white matter lesions. Using a partial crush injury of the adult rat optic nerve as a model, we were able to assess both primary and secondary nerve damage. We show that neurons whose axons were not damaged or only marginally damaged after an acute insult will eventually degenerate as a consequence of their existence in the degenerative environment produced by the injury. This secondary degeneration does not occur in all of the neurons at once, but affects them in a stepwise fashion related to the severity of the damage inflicted. These findings, which may be applicable to the progression of acute or chronic neuropathy, imply that neuroprotective therapy may have a beneficial effect even if there is a time lag between injury and treatment.
Animals↗
Diffuse brain stem gliomas. Are we improving outcome?
We reviewed our experience with diffuse brain stem glioma (dBSG) to evaluate whether any improvement of outcome had occurred in our patients over the years. Of the 24 children referred to our department with suspected dBSG from 1981 to 1997, 5 had a different final diagnosis based on the clinical course. Mean survival in the remainder was 16+/-9.8 months from diagnosis. Survival increased with a longer interval from onset of symptoms to diagnosis (12.9+/-9.0 months with an interval of 1-4 weeks; 19.50+/-10.8 months with a longer interval). Visual symptoms at presentation were associated with a poorer prognosis. Survival was better in the 3- to 5-year age group (at diagnosis). Overall, a trend toward a slight improvement in survival was seen over the years, which we presumptively attribute to the introduction of intensive chemotherapy for these patients. We suggest that chemotherapy may be important in the management of dBSG until a better modality is found.
Adolescent↗
Is infertility after surgery for cryptorchidism congenital or acquired?
We evaluated whether deletions of the DAZ (deleted in azoospermia) gene, abnormal karyotypes or hypogonadotropic hypogonadism (HH) were demonstrable in infertile men who had undergone surgery in childhood for cryptorchidism with a simultaneous testicular biopsy that demonstrated no or almost no germ cells. In six men with infertility after surgery for cryptorchidism, the adult karyotype and analyses for the DAZ gene, serum follicle-stimulating hormone, luteinizing hormone, and testosterone were performed from a peripheral blood sample. Testicular volume was also measured. All patients exhibited a 46,XY karyotype. There were no deletions of the DAZ-gene, no HH and no testicular atrophy. The infertility was thus not proved to be congenital, and consequently, surgical treatment is indicated before the germ cells disappear from undescended testes. This appears to be before 15 months of age.
Adult↗
The human glutaryl-CoA dehydrogenase gene: report of intronic sequences and of 13 novel mutations causing glutaric aciduria type I.
Glutaric acidemia type I (GAI) (McKusick 231670) is an autosomal recessive disease affecting the catabolism of the amino acids lysine, hydroxylysine and tryptophan, caused by a defect in the gene encoding glutaryl-coenzyme A dehydrogenase (GCDH) and associated with severe neurological symptoms. Several pathogenic mutations in GCDH have been reported to cause GAI. One mutation, R402W, is more common than the others, which seem to be private" mutations. Here we report the entire sequences of introns 1, 2, 3, 6, 7, 8 and 9, and part of those of introns 4, 5 and 10 as well as 21 different mutations in 20 patients with GAI, corresponding to 38 out of 40 alleles.
Amino Acid Metabolism, Inborn Errors↗
Elbow arthrography.
Elbow arthrography provides useful information that is not available with noninvasive imaging. This article describes normal elbow anatomy as seen by arthrography. Technical aspects of arthrography with regard to radiographs and CT and MR imaging are reviewed. Indications for MR arthrography include identification of loose bodies, chondral and osteochondral fractures, collateral ligament tears, and synovial and capsular abnormalities.
Arthrography↗
Cholesterol levels long-term after liver transplant.
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Cholesterol↗
Restricted inflammatory reaction in the CNS: a key impediment to axonal regeneration?
Axons in the central nervous system (CNS) of adult mammals do not regenerate after injury. Mammalian CNS differs in this respect from other mammalian tissues, including the peripheral nervous system (PNS), and from the CNS of lower vertebrates. In most parts of the body, including the nervous system, injury triggers an inflammatory reaction involving macrophages. This reaction is needed for tissue healing; when it is delayed or insufficient, healing is incomplete. The CNS, although needing an efficient inflammatory reaction resembling that in the periphery for tissue healing, appears to have lost the ability to supply it. We suggest that restricted CNS recruitment and activation of macrophages are linked to regeneration failure and might reflect the immune privilege that characterizes the mammalian CNS. As macrophages play a critical role in tissue restoration, and because their recruitment and activation are among the most upstream of the events leading to tissue healing, overcoming the deficiencies in these steps might trigger a self-repair processing leading to recovery after CNS injury.
Animals↗
Hemorrhagic necrotic schwannoma presenting as purulent meningitis.
BACKGROUND: Intracranial schwannoma involving the XIIth cranial nerve is rare. We report an unusual clinical presentation and pathological verification of a schwannoma, which had become haemorrhagic and necrotic, simulating acute purulent meningitis. METHODS: A literature review of intracranial tumors presenting as acute purulent meningitis, with emphasis on schwannomas, was undertaken. RESULTS: Few cases of hypoglossal schwannoma have been reported; the association with purulent meningitis has not been previously documented. CONCLUSION: In patients presenting with sterile purulent meningitis, a necrotic tumor should be considered as a possible etiology.
Adult↗
Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats.
Postinjury recovery in most tissues requires an effective dialog with macrophages; however, in the mammalian central nervous system, this dialog may be restricted (possibly due to its immune-privileged status), which probably contributes to its regeneration failure. We circumvented this by implanting macrophages, pre-exposed ex vivo to peripheral nerve segments, into transected rat spinal cord. This stimulated tissue repair and partial recovery of motor function, manifested behaviorally by movement of hind limbs, plantar placement of the paws and weight support, and electrophysiologically by cortically evoked hind-limb muscle response. We substantiated these findings immunohistochemically by demonstrating continuity of labeled nerve fibers across the transected site, and by tracing descending fibers distally to it by anterograde labeling. In recovered rats, retransection of the cord above the primary transection site led to loss of recovery, indicating the involvement of long descending spinal tracts. Injection of macrophages into the site of injury is relatively non-invasive and, as the cells are autologous, it may be developed into a clinical therapy.
Animals↗
Failure of short-term mannose therapy of patients with carbohydrate-deficient glycoprotein syndrome type 1A.
Carbohydrate-deficient glycoprotein syndrome type 1A (CDGS1A) is an inherited disorder with multisystemic abnormalities resulting from failure to generate sufficient lipid-linked oligosaccharide precursor or to transfer the sugar chain to many glycoproteins. Cultured fibroblasts from these patients have reduced incorporation of mannose into glycoproteins which can be corrected by adding D-mannose to the culture medium. Providing dietary mannose to elevate mannose concentrations in vivo therefore might remedy some of the underglycosylation in the patients. Five children with CDGS1A aged 15 months to 14 y completed a protocol of enteral supplementation with D-mannose 100 mg/kg every 3 h for 9 d. The mean S-mannose level increased from 32 microM (range 22-42 microM) to a trough value of 72 microM (range 39-103 microM). No serious side effects were observed. Surprisingly, the mean serum concentration of four glycoproteins (transferrin, alpha1-antitrypsin, antithrombin, and thyroxine-binding globulin) tended to decrease, and the mean serum concentration of carbohydrate-deficient transferrin (CDT) increased. Furthermore, the initially present abnormal isoforms of these glycoproteins and of protein C became more prominent and/or additional abnormal isoforms appeared. This short-term trial does not support a benefit of mannose to the deficient glycosylation of CDGS1A patients.
Adolescent↗