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P Cesaro

Publications and source records attributed to P Cesaro.

At least 19 recordsLinked to original sources
PubMed1995

Rationale for intrastriatal grafting of striatal neuroblasts in patients with Huntington's disease.

Huntington's disease is a genetic disease, autosomal and dominant, that induces motor disorders, an inexorable deterioration of higher brain functions and psychiatric disturbances. At present, there are no known therapeutics against Huntington's disease. The Network of European CNS Transplantation and Restoration (NECTAR) has begun a program aimed at defining the conditions under which intrastriatal transplantation of fetal striatal cells could be attempted as an experimental treatment for Huntington's disease. This review presents the reasons why our group is considering participating in these trials. The validity of this therapeutic approach is supported by three main series of data: (i) neuropathological, clinical and imaging data indicate that Huntington's disease is, above all, a localized affection of a specific neuronal population ("medium-spiny" neurons) in the striatum; (ii) a large body of experimental results, obtained in rats and non-human primates, demonstrates that transplanted fetal striatal cells are able to integrate the host brain and to substitute for previously lesioned host striatal neurons; (iii) expertise in clinical neural transplantation has now been acquired from the treatment of patients with Parkinson's disease. These different sets of data are presented and discussed in this review. There are a number of problems which do not yet appear to be entirely resolved, nor are they likely to be using the experimental models currently available. These problems are identified and explicitly presented as working hypotheses. (1) Anatomo-functional results obtained in rodents and non-human primates with excitotoxic striatal lesions can serve as a basis for the extrapolation of what can be obtained from patients with Huntington's disease. (2). Huntington's disease can be efficiently fought by substituting degenerated striatal neurons alone. (3) Huntington's disease is due to a genetic defect which either hits the neurons that carry it directly or hits them indirectly only after several decades. Transplanted neurons, because they do not carry the gene or because they are of fetal origin, will not be rapidly affected by the ongoing disease process. Given the current state of knowledge, intracerebral transplantation appears to be the most serious opportunity (if not the only one that has been experimentally validated) for clinical improvement to be obtained in patients with Huntington's disease. The purpose of this review is to open a scientific discussion on its experimental bases before actual clinical trials start.

Animals↗
PubMed1991

[Multiple sclerosis. From lesion to symptoms].

Clinical manifestations of multiple sclerosis cannot be exactly correlated with lesions identified by brain imaging, electrophysiology or even anatomy. It is generally accepted that a continuous conduction is possible within some demyelinated fibers, and a conduction block may occur in the CNS white matter without demyelinization. These data explain the possible occurrence of brief, repetitive deficits besides the classical relapses. Among the latter, at least some are not correlated with demyelinization. The knowledge of these mechanisms suggest the possibility of therapy to restore the conduction without a direct action on the demyelinating process.

Animals↗
PubMed1991

Muscle mitochondrial DNA in encephalomyopathy and ragged red fibres: a Southern blot analysis and literature review.

Various mitochondrial DNA abnormalities have been described in patients with encephalomyopathies. We performed Southern blot analysis of skeletal muscle mitochondrial DNA in nine adult patients with clinical features and ragged red fibres suggesting mitochondrial dysfunction. Two patients with encephalomyopathy and two with the MERRF syndrome (myoclonus epilepsy with ragged red fibres) had the normal PvuII restriction pattern of muscle mitochondrial DNA. In contrast, mitochondrial DNA deletion was observed in two of six patients with ophthalmoplegia. One suffered from typical Kearns-Sayre syndrome and the other from isolated external ophthalmoplegia. None of these patients had affected relatives. The detection of mitochondrial DNA deletion in external ophthalmoplegia and their site and size support previously reported data.

Blotting, Southern↗
PubMed1991

Multifocal multinucleated giant cell myelitis in an AIDS patient.

A 19-year-old male intravenous drug abuser, was admitted to hospital with a one-week history of lower limb weakness and urinary retention. He was known to have been HIV-seropositive for 3 years and had been treated for cerebral toxoplasmosis. Neurological examination confirmed flaccid paraparesis with weak ankle jerks and bilateral extensor plantar responses. There was no obvious sensory deficit. Neurological examination was otherwise normal. CSF contained 63 mg/dl protein and 10 leucocytes/mm3. Myelography was normal. He died 1 month later from septic peritonitis. Neuropathological examination showed chronic lesions of toxoplasmosis in brain. Small necrotic foci with myelin loss, proliferation of microglia, macrophages and multinucleated giant cells (MGC) were disseminated in the whole spinal cord, mostly in the white matter, but the brain was spared. Immunohistochemistry demonstrated p24 and p17 HIV antigens in macrophages, MGC and microglial cells. These lesions resemble those of so called 'multifocal giant cell encephalitis'. The present case demonstrates that HIV-related multifocal inflammatory changes may be restricted to the spinal cord and may be a cause of myelopathy in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1990

"Luxury perfusion" with 99mTc-HMPAO and 123I-IMP SPECT imaging during the subacute phase of stroke.

To compare the merits of 123I-isopropyl-iodoamphetamine (123I-IMP) and 99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with 123I-IMP and 99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal 99mTc-HMPAO SPECT and abnormal 123I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on 99mTc-HMPAO in areas corresponding to defects on the 123I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination, 99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on 123I-IMP. Crossed cerebellar diaschisis was found in 7 patients with 99mTc-HMPAO and was absent for both 123I-IMP and 99mTc-HMPAO in 3. We suggest that SPECT with 99mTc-HMPAO could show transient hyperemia not demonstrated by 123I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with 99mTc-HMPAO than with 123I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.

Adult↗
PubMed1990

Diffuse noxious inhibitory controls in man. Involvement of the spinoreticular tract.

In normal subjects, heterotopic painful stimuli induce simultaneous and parallel decreases in the sensation of pain and in the spinal nociceptive flexion (RIII) reflex evoked by electrical stimulation of the sural nerve. This inhibition of the RIII reflex is not seen in tetraplegic patients with clinically complete spinal cord transection, suggesting that supraspinal structures are involved in this type of inhibition, mediated through 'Diffuse Noxious Inhibitory Controls' (DNIC). In the present study, the effects of heterotopic nociceptive stimuli on the RIII reflex were examined in 3 patients with unilateral thalamic vascular lesions and in 3 with Wallenberg's syndrome (WS). In the former, as in normal subjects, nociceptive electrical conditioning stimuli applied to the analgesic hand produced a profound inhibition of the RIII reflex followed by long-lasting after-effects. No inhibition was observed in the WS patients. The same conditioning procedure applied to the nonanalgesic hand of the WS patients resulted in inhibition and after-effects similar to those observed in normal subjects. The fact that noxious but nonpainful stimuli triggered DNIC in the patients with thalamic lesions excludes the possibility that masking of pain by a second painful focus is mainly due to attentional processes. It is also concluded that lemniscal and spinothalamic pathways are not involved in the triggering of DNIC in man and it is suggested that the brainstem and probably the spinoreticular tract are key neuronal links in the loop subserving DNIC in man.

Adult↗
PubMed1990

A case-control epidemiological study of MS in the Paris area with particular reference to past disease history and profession.

A retrospective case-control study was carried out on 230 patients with multiple sclerosis (MS) and 230 controls matched for year of birth and sex. The geographical distribution of residence of MS patients and controls was similar. Two peak ages of onset of MS were observed among woman patients (20-24, 30-34 years). There was no difference in histories of infectious diseases and autoimmune diseases between the two groups. A greater number of hairdressers was noticed among the patient group (p less than 0.05) and three patients (no control) had had professional contact with pathology specimens.

Adolescent↗
PubMed1990

In vitro covalent binding of new brain tracer, para-125I-amphetamine, to rat liver and lung microsomes.

p-125I-amphetamine (I-Amp) is retained significantly in liver and lung during brain tomoscintigraphy. To attempt to explain this clinical observation, we have investigated the interaction of I-Amp with rat liver and lung microsomal proteins. Studies using spectral shift technique indicate that low concentration of I-Amp gives a type I complex and high concentration appears very stable type II complex with cytochrome P-450 Fe III. In the presence of NADPH, I-Amp gives rise to a 455 nm absorbing complex with similar properties to the Fe-RNO complexes. This complex formation was greatly enhanced with phenobarbital treated liver microsomes. The in vitro binding study shows that I-Amp and/or its metabolites was covalently bound to macromolecules in the presence of the molecular oxygen and NADPH-generating system. Incubation in the presence of glutathione, cystein and radical scavengers decreases binding. Mixed function oxydase (MFO) inhibitors diminish the amount of covalent binding and alter the extent of metabolite formation. The total covalent binding level increased with liver microsomes from PB pretreated rats as it was observed with the 455nm complex formation. The radioactivity distribution on microsomal proteins was examinated with SDS polyacrylamide gel electrophoresis and autoradiography. This experiment proves that the radiolabelled compounds are bound on the cytochrome P-450. The radioactivity bound increased when the PB induced rat liver microsomes were used. All these results indicate that I-Amp was activated by an oxydative process dependent on the MFO system which suggests a N-oxydation of I-Amp and the formation of reactive entities which covalently bind to proteins.

Amphetamine↗
PubMed1989

Nonathymulin treatment of multiple sclerosis: double-blind pilot study.

We carried out a randomized, double-blind, placebo-controlled trial of Nonathymulin (NT, synthetic serum thymic factor) in patients with evolutive multiple sclerosis (MS) and moderate disability. Forty matched patients were treated with subcutaneous NT or placebo for 6 months and followed for another 6 months. There was no significant difference in treatment and control groups in the Kurtzke. Disability scores, Ambulation Index and Functional Scale. No significant side effects were recorded. NT is not effective in treating evolutive and moderately disabled MS.

Adult↗
PubMed1988

Tumor-simulating giant serpentine aneurysm of the posterior cerebral artery.

A case of a giant aneurysm of the proximal segment of the posterior cerebral artery is reported. Complete neuroradiologic (computed tomography scan, angiography, magnetic resonance imaging) and pathological studies were performed. This type of aneurysm is extremely rare and may be difficult to differentiate from a cerebral tumor, both clinically and on computed tomography scan. Vertebral angiography is usually necessary to make, or confirm, the diagnosis.

Aged↗
PubMed1987

Early and delayed SPECT using N-isopropyl p-iodoamphetamine iodine 123 in cerebral ischemia. A prognostic index for clinical recovery.

Sixteen patients with stroke, five patients with permanent regressive ischemic neurologic deficit, and three patients with transient ischemic attacks were studied by single photon emission computed tomography performed within the first hour (early scan) and four hours (delayed scan) after injection of N-isopropyl-p-iodoamphetamine-iodine-123 (IMP). These patients were classified into three groups according to their clinical improvement three months later, and results of single photon emission computed tomography were compared with computed tomographic scan results and correlated to the clinical outcome. Regional brain hypoactivity of IMP differed in some cases between early and delayed IMP scans, showing in those cases a "redistribution" activity. The amplitude of this redistribution was significantly correlated with the clinical outcome of patients with stroke, whereas the value of hypoactivity on early IMP scan did not show such a correlation. The higher the redistribution amplitude was, the better was the clinical outcome. Comparative regional brain hypoactivity of IMP on early and delayed scans could represent a prognostic index of clinical recovery inasmuch as it gives information concerning viability of ischemic brain tissue.

Adult↗
PubMed1987

Amines for brain tomoscintigraphy.

Amines like N-isopropyl-p-123I-iodoamphetamine (IMP) and hydroxy 123I-iodobenzyl propyl diamine (HIPDM) associated with brain tomoscintigraphy have proved their worth for detecting ischaemic abnormalities. Even though the chemistry of their metabolism and their biodistribution are not fully understood, their application in the study of parenchymal impairment in stroke and reversible ischaemia yields additional information compared to the other methods of imaging like CT or MRI. The concept of a steady state in brain with a wash in/wash out model has been considered especially with IMP, to explain the evolution of the activity pattern with time when comparing early and delayed images. (This review leads to foresee the prognosis of of ischaemic diseases when redistribution is taken into account.)

Amphetamines↗
PubMed1987

Temporal evolution of brain distribution of IMP and HIPDM. Concise communication.

Early and late brain distribution of iodine-labelled N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine (HIPDM) and iodine labelled N-isopropyl-p-iodoamphetamine (IMP) were compared in rat and one human patient with a recent stroke in the right middle cerebral artery area. In rat, an important 'redistribution' of cerebral activity was observed in various areas of the brain, mainly white matter, whereas no such observation was made with HIPDM. In the patient, the right area was hypoactive during the early SPECT with IMP and HIPDM, and redistribution was observed in the late SPECT only with IMP. We suggest that while HIPDM appears to reflect regional cerebral perfusion, IMP distribution is dependent upon metabolic brain activity.

Aged↗
PubMed1986

Monstrocellular heavily lipidized malignant glioma.

A man of 32 years was admitted with a 3-month history of temporal lobe epilepsy. CT-Scan showed a well-circumscribed area of heterogenous contrast enhancement in the right temporal lobe. Gross total resection was performed but the tumor recurred: the patient died 6 months after the onset of symptoms. There was no autopsy. Histology revealed a highly pleomorphic neoplasm with extensive zones of necrosis. Monster cells, up to several hundred micrometers in diameter, with multiple and/or multi-lobed nuclei were numerous and showed emperipolesis for polymorphonuclear, mononuclear, and small tumor cells. Abundant mitoses were observed. Tumor cells of all sizes had ground-glass or vacuolated cytoplasm which obscured their glial nature. GFAP was demonstrated in some neoplastic cells. Reticulin fibers were confined to perivascular areas where mononuclear inflammatory cells were sometimes noted. Vascular proliferation was mild. Electromicroscopic study revealed that the cytoplasms of the tumor cells contained abundant lipid droplets, numerous mitochondria, and glio-filaments. Such a tumor has been reported recently as "malignant glioma with heavily lipidized tumor cells". This rare entity, previously reported as xanthosarcoma of the brain, represents a subgroup of primitive monstrocellular cerebral tumors.

Adult↗