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J J López-Lozano

Publications and source records attributed to J J López-Lozano.

10 recordsLinked to original sources

Subgroups of parkinsonian patients differentiated by peptidergic immunostaining of caudate nucleus biopsies.

In this study, Met-enkephalin (Met-enk), substance P (SP) and tyrosine hydroxylase (TH) immunostaining was assessed in caudate nucleus biopsies from 15 Parkinson's disease patients who were treated surgically. According to the combination of changes in Met-enk, SP and TH immunostaining, several subgroups of parkinsonian patients were disclosed. Group I: Patients showing low SP and normal Met-enk immunostaining, and variably reduced TH immunoreactivity. Group II: both SP and Met-enk immunostaining were apparently of normal intensity in these PD patients, but they showed the greatest decrease in TH labeling. Group III: PD patients that showed normal SP, very low Met-enk and variably reduced TH immunostaining. Low Met-enk immunostaining tended to correlate with the severity of the disease as judged by higher Unified Parkinson's disease Rating Scale and gait scores. These results suggest that different neurochemical phenotypes may exist among Parkinson's disease patients. Peptidergic deficits should be taken into account for therapeutic intervention.

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Clinical outcome of cotransplantation of peripheral nerve and adrenal medulla in patients with Parkinson's disease. Clínica Puerta de Hierro Neural Transplantation Group.

OBJECT: Transplants of adrenal medulla (AM) and fetal ventral mesencephalon (FVM) are currently being tested as therapeutic alternatives in patients with Parkinson's disease (PD). At the Clínica Puerta de Hierro in Madrid, a controlled clinical trial is underway to establish which donor tissue, if any, is the best for open surgical implantation in patients with PD. METHODS: Since 1987, varying degrees of clinical improvement have been achieved in Grade IV and V parkinsonian patients by implanting perfused AM and FVM into the right caudate nucleus. To investigate further whether implantation of different types of donor tissues results in qualitatively and quantitatively different degrees of recovery, four patients with Grade IV or V PD received implants of pre-coincubated autologous AM and intercostal nerve in the caudate nucleus. Four nonsurgically treated patients served as a control group. Three years posttransplantation, longer on phases (46.2%+/-10.4% of the day presurgery to 87.5%+/-10.4% of the day 36 months postsurgery) and improved symptoms in on and off phases persist in all four cases, with reduced dyskinesias (67.1%+/-9.2% of the day in on phases presurgery to 17%+/-13.8% of the day in on phases 36 months postsurgery). Progress appears to be stepwise, starting within weeks of tranplantation and becoming clinically significant in the 2nd and 3rd months (similar to our AM- and sooner than in our FVM-implanted patients), followed by a period of stability and, after a second wave of improvement 12 to 18 months posttransplantation (similar to FVM implants), has continued (87.5+/-7 points presurgery to 46+/-5.6 points 36 months postsurgery). In the experimental group, doses of levodopa have been reduced by more than 60% and dopamine agonist use has not resumed. In contrast, there have been no significant clinical changes in the control group. CONCLUSIONS: Implantation of tissue other than fetal tissue can promote a long-term improvement in the clinical symptomatology of seriously disabled parkinsonian patients. This finding is supported by the autopsy report of a patient with PD who had undergone grafting of AM plus peripheral nerve in which it was demonstrated that a large number of tyrosine hydroxylase-positive cells survive 1 year after implantation. In addition, there was a dense network of host dopaminergic fibers around the graft.

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Long-term improvement in patients with severe Parkinson's disease after implantation of fetal ventral mesencephalic tissue in a cavity of the caudate nucleus: 5-year follow up in 10 patients. Clinica Puerta de Hierro Neural Transplantation Group.

Different groups worldwide have observed in recent years that stereotactic implantation of fetal tissue can ameliorate the clinical symptoms of Parkinson's disease. The authors therefore investigated whether implantation of fetal ventral mesencephalic (FVM) tissue via open surgery is also capable of producing an improvement and whether this improvement is transient or long lasting. The authors report their findings in a 5-year follow-up study in 10 patients with Hoehn and Yahr Grade IV or V Parkinson's disease in whom a single FVM graft was implanted in a cavity created in the right caudate nucleus. The results indicate that the implants improved motor function and that clinical recovery persisted in seven of the 10 patients 5 years after implantation. Amelioration was observed in both the on and off phases and was accompanied by a 64% reduction in the levodopa dose and withdrawal of the dopamine agonist. The on phase was prolonged from 39% of the waking day to 72%, with reduced intensity and duration of dyskinesias. All symptoms that were analyzed showed improvement, although they differed in intensity and time of onset. The course of improvement seemed to be stepwise, with significant improvement between 5 and 7 months postimplantation followed by two waves of progress peaking in Months 15 and 36. Withdrawal of cyclosporine in three patients after more than 2 years of administration produced a decline in the patients' clinical conditions. In conclusion, the results indicate that open surgery implantation of FVM tissue in the caudate nucleus improves the clinical condition of parkinsonian patients and that this improvement can persist for at least 5 years. In comparison with two earlier series reported by the authors, which involved implants of perfused adrenal medulla and coimplantation of adrenal medulla and peripheral nerve, the course and pattern of improvement in these implant recipients suggests that their recovery can be attributed to more than one factor.

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Clinical experience with cotransplantation of peripheral nerve and adrenal medulla in patients with Parkinson's disease.

Coimplants of adrenal medulla (AM) and peripheral nerve (PN) in animal models of Parkinson's disease (PD) have shown that AM cells survive longer, tend to show neuronal phenotype, and enhance sprouting of host fibers. Since 1987, our implants of perfused AM and fetal ventral mesencephalon (FVM) in PD patients have achieved varying degrees of clinical improvement. If the donor tissue determines the improvement, different types of implants should result in qualitatively and quantitatively different degrees of improvement. The purpose of this study is to determine whether or not the clinical course, improvement slope, and reduction of medication observed in PD patients who undergo tissue transplantation (Tx) depend on the donor tissue type. In a pilot study, four grade IV-V PD patients received implants of precoincubated autologous AM and intercostal nerve in the caudate nucleus (open surgery). Clinical assessment was based on international scales (UPD) as reported for Tx of FVM and perfused AM. There were no systemic or neurologic complications. Four years post-Tx, longer On phases and improved PD symptoms (ADL and motor-UPD) in On and Off persist in four cases, with reduced dyskinesias. Progress appears to be stepwise, starting within weeks of Tx (similar to AM and sooner than our FVM implants), followed by a period of stability and, after a second wave of improvement 12-18 months post-Tx (similar to FVM implants), continues to date. L-dopa medication has been reduced by more than 60% and dopamine agonist use has not resumed. We conclude that our recipients continue to be clinically better than prior to Tx. The course of recovery after co-Tx of AM and PN differs from that of FVM or AM implants. This fact may be related to the etiological factors that produce the improvement.

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Grafting of perfused adrenal medullary tissue into the caudate nucleus of patients with Parkinson's disease. Clinica Puerta de Hierro Neural Transplantation Group.

The authors report results obtained in 20 severely affected patients with Parkinson's disease (Grade IV or V) who received an autotransplant of perfused adrenal medullary tissue. This study seems to indicate that these autoimplants can improve the parkinsonian symptomatology and induce amelioration in the patients' performance of routine activities. All the symptoms analyzed showed improvement, although it differed in intensity and time of onset. Moreover, this improvement was accompanied by a reduction in the daily intake of L-dopa, with discontinuance of dopamine agonists and amantadine. A number of medical complications were encountered, including three deaths, probably related to performing abdominal surgery in seriously affected parkinsonian patients who were unable to tolerate the discontinuance of their medication. The transient psychiatric disorders observed appeared to be related to the postoperative dose of L-dopa and/or anticholinergic agents administered, and diminished or disappeared when the doses were reduced. The reasons for improvement, which was bilateral, remain unknown, although one cause may be the surgical trauma (minicaudotomy) together with the implantation of adrenal medullary tissue, which may promote the sprouting of surviving dopaminergic fibers. Moreover, in this series, perfusion of adrenal medulla increased the capacity for revascularization of the tissue and may have reduced the damaging effects of warm ischemia on the cells. This, together with the existence of fenestrated vessels, could hypothetically have served as an access point for drugs, and if the implanted cells were viable, they might have served to store and manufacture different factors and/or transmitters. These results as well as those of other groups justify the development of a controlled international clinical trial.

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Preparation of adrenal medullary tissue for transplantation in Parkinson's disease: a new procedure. Technical note.

The authors describe a technique by which adrenal medullary tissue can be easily dissected from the adrenal cortex. The method involves perfusion with Locke's modified buffer, dissection of adrenal gland in buffer free of calcium or magnesium, and storage in a culture medium before implantation into the caudate nucleus of patients with Parkinson's disease. This method seems to increase the viability and purity of adrenal medullary tissue. The results obtained in 15 parkinsonian patients implanted with perfused adrenal medulla indicate the potential value of this technique.

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[Neural transplants en Parkinson disease: clinical results of 10 years of experience. Group of Neural Transplants of the CPH].

INTRODUCTION: At the end of the 1970s people considered the possibility that transplants might be useful to replace degenerate specific cell populations, such as the mesencephalic dopaminergic neurones in Parkinson's disease (PD). Since then this has become an experimental alternative treatment for patients with degenerative diseases. The history of transplants of catecholamine producing tissues within the brain of patients with PD started in 1985, when Backlund et al published the results of the first implants of autologous adrenal medulla in two patients with Parkinsonism. Since then, many patients throughout the world have benefited from the results obtained using this method. Two main types of tissue have been used in this method: autologous adrenal medulla and human foetal ventral mesencephalic tissue. DEVELOPMENT: In this paper we first review the clinical effects of the diverse types of transplant done to date. Then in the second part we give a summary of the clinical results obtained by our group with the different types of transplant carried out. We explain their evolution, original hypothesis and justify the reasons which led us to use three different types of donor material: autologous adrenal medulla, fetal tissue and adrenal medulla co-incubated with peripheral nerve. Then, after showing that the clinical improvement is different depending on the type of tissue transplanted, we comment on the probable reason for the improvement seen in patients with implants. CONCLUSION: The transplantation of nervous tissue seems to us to be no longer an experimental alternative for the treatment of PD but has become an effective, lasting treatment for patients with Parkinson's disease.

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