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1
المؤلفون: Haruo Okazaki, Patrick J. Kelly, Jon A. van Heerden, Susan L. Stoddard, Gertrude M. Tyce, J. Eric Ahlskog, Stephen W. Carmichael, Albert N. Nelson, Elliott Richelson
المصدر: Annals of Neurology. 30:185-191
مصطلحات موضوعية: Adult, Spiperone, medicine.medical_specialty, Caudate nucleus, Down-Regulation, Receptors, Dopamine, Levodopa, Dopamine, Dopamine receptor D2, Internal medicine, Muscarinic acetylcholine receptor, Muscarinic acetylcholine receptor M4, Humans, Medicine, Brain Tissue Transplantation, Receptors, Cholinergic, Receptor, Bromocriptine, Pergolide, Receptors, Dopamine D2, business.industry, Parkinson Disease, Middle Aged, Receptors, Muscarinic, Receptors, Neurotransmitter, Quinuclidinyl Benzilate, Endocrinology, Neurology, Neurology (clinical), Caudate Nucleus, business, medicine.drug
الوصف: Binding of spiperone and 3-quinuclidinyl benzilate (QNB), both labeled with hydrogen 3 (3H), were measured in caudate tissue obtained from 8 living parkinsonian patients at the time of cerebral transplantation. This was clinically homogeneous group of patients. All remained predominantly responsive to levodopa, although with marked disability secondary to clinical fluctuations (short-duration responses) and medication-induced dyskinesias; all were receiving substantial doses of levodopa and 6 of the 8 patients were additionally receiving bromocriptine or pergolide. Binding densities of dopamine D2 receptors, as measured by [3H]spiperone binding, were reduced in this group of patients, compared to caudate specimens from autopsy control subjects. This findings may reflect medication-induced receptor downregulation. Parallel changes occurred with muscarinic cholinergic receptors; [3H]QNB binding was significantly reduced, compared to autopsy control values. This reduction of muscarinic receptors might be due to loss of nigrostriatal terminals that are known to contain muscarinic receptors. Alternatively, muscarinic receptors may have been downregulated by increased corticostriatal glutamatergic input to cholinergic cells, inferred to be present based on the prominent levodopa-induced dyskinesias. Finally, receptor deficits could have been a reflection of more widespread degenerative cerebral disease, although levodopa-refractory symptoms were generally not pronounced in these patients.
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2
المؤلفون: Patrick J. Kelly, Gertrude M. Tyce, Patricia A. Bailey, Marceil D. Blexrud, Stephen W. Carmichael, Anthony J. Windebank, Susan L. Stoddard, Jon A. van Heerden, Gaye N. Bell, J. Eric Ahlskog
المصدر: Mayo Clinic proceedings. 65(3)
مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Epinephrine, Hydrocortisone, Dopamine, Caudate nucleus, Levodopa, Norepinephrine, chemistry.chemical_compound, Internal medicine, Activities of Daily Living, medicine, Humans, Nerve Growth Factors, Cells, Cultured, Movement Disorders, business.industry, Homovanillic acid, Homovanillic Acid, Parkinson Disease, General Medicine, Middle Aged, Transplantation, Endocrinology, medicine.anatomical_structure, chemistry, Adrenal Medulla, Caudate Nucleus, business, Adrenal medulla, Glucocorticoid, medicine.drug, Follow-Up Studies
الوصف: Transplantation of adrenal medulla into the caudate nucleus as treatment for Parkinson's disease was performed in eight patients. Although our previous 6-month follow-up revealed early modest improvement, an extension of that follow-up to 1 year disclosed no additional gains in any patient. At the end of 1 year, only one patient could be categorized as moderately improved; three patients were mildly improved, and four patients were unimproved. The rationale for transplanting adrenal medulla was to reestablish a physiologic source of dopamine to the striatum. We measured cerebrospinal fluid (CSF) and plasma catecholamines and metabolites before and after transplantation. Conjugated dopamine (the predominant form of dopamine found in the CSF) and homovanillic acid (the major dopamine metabolite) were modestly and inconsistently increased in the CSF. Conjugated and free epinephrine and norepinephrine, as well as 3-methoxy-4-hydroxyphenylglycol concentrations were not increased in CSF after graft placement, an indication that the adrenal chromaffin cells were no longer producing high levels of these nondopamine catecholamines and metabolites. CSF cortisol concentrations were not increased after transplantation, compared with values from controls, consistent with low numbers of functioning adrenal cortical cells contaminating the graft (or poor survival). Posttransplantation CSF did not induce a neurotrophic effect in cell cultures of 15-day embryonic rat dorsal root ganglion or PC12 (rat pheochromocytoma) cell lines. Survival of samples of patients' adrenal medullary tissue for 2 weeks in tissue culture attested to the viability of the graft at the time of transplantation. The relative concentrations of dopamine to epinephrine or norepinephrine increased in these cultured adrenal medullary cells, presumably because of loss of the glucocorticoid influence on catecholamine synthesis. A wide variety of factors could have contributed to our failure to replicate the earlier impressive results of adrenal-to-brain transplantation reported by others. Continued transplantation studies in animal models of parkinsonism are necessary for better elucidation of these factors.
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المؤلفون: Stephen W. Carmichael, Patrick J. Kelly, Susan L. Stoddard, J. Eric Ahlskog, Jon A. van Heerden, Gaye N. Bell
المصدر: Mayo Clinic Proceedings. 64:282-290
مصطلحات موضوعية: Adult, Male, Dyskinesia, Drug-Induced, medicine.medical_specialty, Levodopa, Parkinson's disease, Caudate nucleus, Placebo, Stereotaxic Techniques, Postoperative Complications, medicine, Humans, business.industry, Carbidopa, Parkinson Disease, General Medicine, Perioperative, Middle Aged, medicine.disease, Surgery, Transplantation, Drug Combinations, Dyskinesia, Adrenal Medulla, Caudate Nucleus, medicine.symptom, business, Somnolence, Follow-Up Studies, medicine.drug
الوصف: In eight patients with advanced Parkinson's disease, we performed autograft transplantation of adrenal medulla to the head of the caudate nucleus. Our technique was similar to that developed by Madrazo and co-workers in Mexico City. No major perioperative complications occurred except for somnolence in one patient for 8 days postoperatively. The follow-up period has been at least 6 months in seven of the patients, and only limited benefit has been apparent. The early morning Parkinson examination score in the "off" (unmedicated) state was significantly improved in one patient and slightly better in the other six. Diary card entries suggested a mild trend toward improvement (not statistically significant). Four of the seven patients were taking less levodopa 6 months after the operation than they had been preoperatively; three of five patients were no longer taking dopamine agonists postoperatively. We cannot exclude a placebo effect contributing to any of this improvement. A reduction in medication-induced dyskinesia was also noted, but this result may have been due to adjustments in doses or a slightly less potent effect of medication (or both factors). In summary, we have not yet been able to replicate the dramatic success reported for adrenal medullary transplantation by Madrazo's group, although our patients may have experienced mild to moderate improvement. We continue to maintain follow-up surveillance of these patients.
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المؤلفون: Alan R. Zinsmeister, Gertrude M. Tyce, Patrick J. Kelly, Susan L. Stoddard, Stephen W. Carmichael, Jon A. van Heerden, J. Eric Ahlskog
المصدر: Experimental Neurology. 104:218-222
مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Pathology, Medullary cavity, medicine.medical_treatment, Urology, Caudate nucleus, Nephrectomy, Transplantation, Autologous, Catecholamines, Developmental Neuroscience, Renal cell carcinoma, medicine, Humans, Autologous transplantation, business.industry, Parkinson Disease, Middle Aged, medicine.disease, Transplantation, medicine.anatomical_structure, Neurology, Adrenal Medulla, Catecholamine, Adrenal medulla, business, medicine.drug
الوصف: Adrenal medullary catecholamines were measured in tissue samples from eight patients who underwent autologous transplantation of the adrenal medulla to the caudate nucleus as a treatment for Parkinson's disease. These adrenal catecholamine levels were compared to a group of patients of similar age who underwent unilateral nephrectomy for renal cell carcinoma. The levels of each catecholamine, expressed as nanomoles per milligram wet weight tissue, were significantly lower (P less than or equal to 0.005) in the parkinsonian patients than in the nephrectomy patients. These observations support data reported previously from autopsy specimens and suggest that the adrenal medullae of parkinsonian patients may be a compromised source of dopamine-producing tissue; this may limit its effectiveness in eliciting maximum clinical improvement following transplantation.
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المؤلفون: Patrick J. Kelly, Stephen W. Carmichael, Ahlskog Je, J A van Heerden, Gertrude M. Tyce, Susan L. Stoddard
المصدر: Experimental neurology. 105(2)
مصطلحات موضوعية: Adult, Male, Levodopa, Serum albumin, Blood–brain barrier, Capillary Permeability, Cerebrospinal fluid, Developmental Neuroscience, Medicine, Humans, CSF albumin, Serum Albumin, Meglumine, biology, business.industry, Osmolar Concentration, Brain, Carbidopa, Parkinson Disease, Middle Aged, Transplantation, medicine.anatomical_structure, Neurology, Adrenal Medulla, Blood-Brain Barrier, Anesthesia, Immunoglobulin G, biology.protein, Caudate Nucleus, business, Tomography, X-Ray Computed, medicine.drug
الوصف: Cerebrospinal fluid (CSF) and serum or plasma concentrations of albumin, IgG and carbidopa were measured before and after adrenal-brain transplantation in patients with Parkinson's disease to indirectly assess blood-brain barrier (BBB) integrity. Previous studies in animals have suggested that the BBB is compromised by cerebral transplantation. CSF and plasma levodopa was also measured to permit comparison with the carbidopa values, recognizing that levodopa readily crosses the BBB via facilitated transport. Our patients underwent adrenal-brain transplantation in accordance with the method of Madrazo et al. (I. Madrazo, R. Drucker-Colin, V. Diaz, J. Martinez-Mata, C. Torres, and J. J. Becerril, 1987, N. Engl. J. Med. 316: 831-834) in which adrenal medullary pieces are implanted in the head of the caudate nucleus, in contact with the cerebrospinal fluid. All patients were maintained on oral carbidopa/levodopa therapy after surgery. CSF albumin/serum albumin and CSF IgG/serum IgG ratios were initially elevated above the preoperative baseline 6 weeks after the surgery; however, these values returned to the preoperative baseline by 6 months following the operation in six of seven patients. This suggested that the BBB was sufficiently intact to exclude these larger protein molecules from the CSF of these six patients. On the other hand, exogenously administered carbidopa, which normally is largely excluded from the cerebrospinal fluid by the BBB, was modestly increased in the CSF in four of the five patients in which it was measured. This suggests that the transplant BBB might be partially patent to small molecules for at least 6 months after the surgery. Whether increased passage of carbidopa into CSF and perhaps the transplant is of clinical significance has yet to be determined. Median CSF levodopa did not increase after surgery, probably because a limited defect in the BBB would be likely to be overshadowed by the effects of facilitated transport. CT scans performed following intravenous iothalamate meglumine contrast failed to reveal enhancement (dye leakage) near the transplantation site; however, artifact from the metal surgical clips used in the Madrazo procedure prevented good visualization of the area.
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المؤلفون: Tony L. Yaksh, Gertrude M. Tyce, Melton Lj rd, Haruo Okazaki, Stephen W. Carmichael, Stoddard Sl, Wilson Rj, Ahlskog Je, Brimijoin Ws
المصدر: The New England journal of medicine. 318(4)
مصطلحات موضوعية: Adult, medicine.medical_specialty, Adolescent, business.industry, Parkinsonism, Parkinson Disease, General Medicine, Middle Aged, medicine.disease, Endocrinology, medicine.anatomical_structure, Text mining, Catecholamines, Adrenal Medulla, Internal medicine, medicine, Humans, business, Adrenal medulla, Aged
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7
المؤلفون: Stephen W. Carmichael, Alan R. Zinsmeister, Ahlskog Je, Susan L. Stoddard, Gertrude M. Tyce
المصدر: Experimental neurology. 104(1)
مصطلحات موضوعية: Male, medicine.medical_specialty, Epinephrine, Dopamine, Autopsy, Norepinephrine, chemistry.chemical_compound, Degenerative disease, Catecholamines, Developmental Neuroscience, Internal medicine, medicine, Humans, Neurotransmitter, Aged, Aged, 80 and over, business.industry, Parkinson Disease, Middle Aged, medicine.disease, nervous system diseases, Endocrinology, medicine.anatomical_structure, Neurology, chemistry, Adrenal Medulla, Catecholamine, Female, Adrenal medulla, business, medicine.drug
الوصف: Autopsy specimens of adrenal medullae from parkinsonian and nonparkinsonian patients were analyzed for free catecholamines by high-performance liquid chromatography with electrochemical detection. The total free catecholamine content (nanomoles free catecholamine per milligram protein) was significantly lower in the parkinsonian patients than in the control population when the values were corrected for age and time from death to organ harvest. It is not established whether this decreased catecholamine content in the adrenals of parkinsonian patients is a concomitant of the disease itself or whether it is secondary to drug therapies used to treat the symptoms of Parkinson's disease.
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