Neural transplantation and trophic factors in Parkinson's disease: special reference to chromaffin cell grafting, NGF support from pretransected peripheral nerve, and encapsulated dopamine-secreting cell grafting.

Since adrenal medullary chromaffin cells produce catecholamines as wel l as several kinds of neurotrophic factors which affect dopamine neurons, the authors have investigated the methods to increase the survival of grafted chromaffin cells in parkinsonian model animals. Measurement of nerve growth factor (NGF) showed that NGF level at the distal stump of the pretransected peripheral nerve increased significantly, thus, we have applied cografting of chromaffin cells with this stump of the peripheral nerve to animal models of Parkinson's disease since chromaffin cell survival have been reported to be increased by supplementation of nerve growth factor (NGF) in vitro and in vivo. By this cografting approach, not only the chromaffin cell survival but also the host intrinsic dopaminergic system recovery were enhanced. This effect continued 2 years in our long-term study The effects of donor and host ages were investigated and the results showed that the effects were more prominent when young donors or hosts were used compared with aging donors or hosts. Although cografting of adrenal medulla with peripheral nerve was applied successfully in parkinsonian patients with favorable results, it may be difficult to apply this procedure in aged patients since this is autografting and adrenal medulla itself may be affected by the disease in aged patients. Polymer-encapsulated dopamine-secreting cells are another donor candidates and can be applied combined with stereotaxic thalamotomy or pallidotomy for the patients with Parkinson's disease in the near future.

NGF-like trophic support from peripheral nerve for grafted rhesus adrenal chromaffin cells.

Autopsy results on patients and corresponding studies in nonhuman primates have revealed that autografts of adrenal medulla into the striatum, used as a treatment for Parkinson's disease, do not survive well. Because adrenal chromaffin cell viability may be limited by the low levels of available nerve growth factor (NGF) in the striatum, the present study was conducted to determine if transected peripheral nerve segments could provide sufficient levels of NGF to enhance chromaffin cell survival in vitro and in vivo. Aged female rhesus monkeys, rendered hemiparkinsonian by the drug MPTP (n-methyl-4-phenyl-1,2,3,6 tetrahydropyridine), received autografts into the striatum using a stereotactic approach, of either sural nerve or adrenal medulla, or cografts of adrenal medulla and sural nerve (three animals in each group). Cell cultures were established from tissue not used in the grafts. Adrenal chromaffin cells either cocultured with sural nerve segments or exposed to exogenous NGF differentiated into a neuronal phenotype. Chromaffin cell survival, when cografted with sural nerve into the striatum, was enhanced four- to eightfold from between 8000 and 18,000 surviving cells in grafts of adrenal tissue only up to 67,000 surviving chromaffin cells in cografts. In grafts of adrenal tissue only, the implant site consisted of an inflammatory focus. Surviving chromaffin cells, which could be identified by both chromogranin A and tyrosine hydroxylase staining, retained their endocrine phenotype. Cografted chromaffin cells exhibited multipolar neuritic processes and numerous chromaffin granules, and were also immunoreactive for tyrosine hydroxylase and chromogranin A. Blood vessels within the graft were fenestrated, indicating that the blood-brain barrier was not intact. Additionally, cografted chromaffin cells were observed in a postsynaptic relationship with axon terminals from an undetermined but presumably a host origin.

The significance of pelvic and para-aortic lymphadenectomy in the operative treatment of ovarian cancer.

Since 1980, 95 of 320 patients with ovarian cancer of Stages I to IV have undergone pelvic lymphadenectomy. A further 57 patients underwent pelvic and para-aortic lymphadenectomy. In the last three years, 83% of patients with Stage III disease had a lymphadenectomy, and 34% had no gross residual tumour after surgery. This entailed bowel resection in 33% of cases. After cytoreduction and chemotherapy, actuarial 5-year survival in Stages I and II was 90%, and was just over 40% in Stage III. Patients with positive nodes had markedly poorer survival than did those with negative nodes. Three years after only pelvic lymphadenectomy, 36.7% of patients with Stage III disease had no clinical, radiological or biochemical evidence of disease. If the abdomen had been cleared of gross disease at surgery, 70% of the patients had no evidence of disease at 3 years. The therapeutic effect of lymphadenectomy is also reflected in the marked improvement in survival of all patients with Stage III ovarian cancer after the introduction of lymphadenectomy.

[Residual arterial hypertension after excision of an extra-adrenal pheochromocytoma]. / Hypertension artérielle résiduelle après exérèse d'un phéochromocytome extra-surrénalien.

Residual arterial hypertension after excision of a pheochromocytoma of the Zuckerkandl organ, has brought the problem of its etiology. The short term approach consisted in performing, after specific biochemical dosages, a scintigram with IMBG, a scan and a magnetic resonance imaging, to look for a second pheochromocytoma. A negative workup enabled to conclude to an essential arterial hypertension. Nevertheless, this does not exclude the possibility of a long term malignancy, requiring clinical monitoring and IMBG scintigraphy.

Spectrum of catecholamine-secreting tumors of the organ of Zuckerkandl.

In a series of 24 pheochromocytomas, four were tumors in the organ of Zuckerkandl. Their presenting symptoms of headache, palpitation, diaphoresis, and anxiety were similar to symptoms of adrenal pheochromocytomas. Two patients had paroxysmal and two patients sustained hypertension. All four had elevated urinary vanillylmandelic acid, metanephrine or catecholamine levels. Two of the tumors were localized with angiography before the availability of computerized tomography. Two patients underwent initial computerized tomography, which was nondiagnostic. Later scans looking specifically for organ of Zuckerkandl tumors were positive. Organ of Zuckerkandl tumors, like other ectopic pheochromocytomas, have a higher rate of malignancy. Two of the four were malignant tumors. One patient died 4 years after operation, but the other patient remains stable despite metastatic disease 8 years after operation. The two patients with benign tumors remain well 2 and 3 years after resection and treatment with alpha-blockade.