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1.
J Clin Oncol ; 17(7): 2208-12, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10561277

ABSTRACT

PURPOSE: To determine the maximum-tolerated dose, dose-limiting toxicities, and potential antitumor activity of twice-weekly gemcitabine and concurrent radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Nineteen patients with histologically confirmed adenocarcinoma of the pancreas were studied at the Wake Forest University Baptist Medical Center and the University of North Carolina at Chapel Hill. The initial dose of gemcitabine was 20 mg/m(2) by 30-minute intravenous infusion each Monday and Thursday for 5 weeks concurrent with 50.4 Gy of radiation to the pancreas. Gemcitabine doses were escalated in 20-mg/m(2) increments in successive cohorts of three to six additional patients until dose-limiting toxicity was observed. RESULTS: The dose-limiting toxicities at 60 mg/m(2) given twice-weekly were nausea/vomiting, neutropenia, and thrombocytopenia. Twice-weekly gemcitabine at a 40-mg/m(2) dose was well tolerated. Of the eight patients eligible for a minimum follow-up of 12 months, three remain alive, one of whom has no evidence of disease progression. CONCLUSION: A dose of twice-weekly gemcitabine at 40 mg/m(2) produced mild thrombocytopenia, neutropenia, nausea, and vomiting when delivered with concurrent radiation to the upper abdomen in patients with advanced pancreatic cancer. These data suggest this regimen is well tolerated and may possess significant activity. These data and other observations have resulted in a phase II Cancer and Leukemia Group B study to ascertain the efficacy of this treatment regimen in patients with locally advanced pancreatic cancer.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Deoxycytidine/analogs & derivatives , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/pharmacology , Combined Modality Therapy , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Dose-Response Relationship, Drug , Humans , Middle Aged , Gemcitabine
2.
Stereotact Funct Neurosurg ; 72(2-4): 219-24, 1999.
Article in English | MEDLINE | ID: mdl-10853081

ABSTRACT

This study was undertaken to investigate the outcomes, complication rates and risk factors of stereotactic intrastriatal neurotransplantation for Parkinson's disease (PD). Bilateral stereotactic neurotransplantation was performed (as previously described) in 60 patients with idiopathic PD. Clinical outcome was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS). The incidence of complication was evaluated by retrospective analysis of the clinical outcomes of the transplanted patients. Patients demonstrated significant improvement in UPDRS scores 12 months after transplantation. Nine patients experienced adverse effects after neurotransplantation, 3 requiring surgical intervention. Patients showed a significant overall improvement and no greater incidence of risk than that of other intracranial procedures.


Subject(s)
Brain Tissue Transplantation , Fetal Tissue Transplantation , Parkinson Disease/surgery , Stereotaxic Techniques , Aged , Antiparkinson Agents/therapeutic use , Brain Damage, Chronic/epidemiology , Brain Damage, Chronic/etiology , Brain Diseases/epidemiology , Brain Diseases/etiology , Brain Tissue Transplantation/adverse effects , Cerebral Hemorrhage/epidemiology , Cerebral Hemorrhage/etiology , Combined Modality Therapy , Cysts/epidemiology , Cysts/etiology , Female , Fetal Tissue Transplantation/adverse effects , Humans , Incidence , Male , Middle Aged , Parkinson Disease/drug therapy , Postoperative Complications/epidemiology , Seizures/epidemiology , Seizures/etiology , Surgical Wound Infection/epidemiology , Surgical Wound Infection/etiology , Treatment Outcome
3.
Stereotact Funct Neurosurg ; 70(1): 19-31, 1998.
Article in English | MEDLINE | ID: mdl-9691238

ABSTRACT

Surgical interventions have been employed to alleviate symptoms of Parkinson's disease (PD) for decades, with improving success. One such treatment has been pallidotomy, the lesioning of a portion of the globus pallidus. Early pallidotomy procedures have paved the way for more accurately targeted methods. Technological advancements in imaging and targeting have made modern pallidotomy a safe and well-tested means of treating PD patients that has reliably positive results. Numerous group studies in recent years have demonstrated effective relief of PD symptoms, and the neuroanatomical and physiological aspects which underlie its effects are being elucidated as well. Recent descriptions of pallidotomy as an experimental procedure must therefore be considered in light of these reports. This review will examine the development of the pallidotomy procedure and the neuroanatomical rationale which underlies it, and discuss recent studies of its efficacy in PD patients.


Subject(s)
Globus Pallidus/surgery , Parkinson Disease/surgery , Basal Ganglia/physiopathology , Forecasting , Humans , Levodopa/therapeutic use , Parkinson Disease/drug therapy , Parkinson Disease/physiopathology , Treatment Outcome
4.
Exp Neurol ; 149(1): 97-108, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9454619

ABSTRACT

Fetal neural transplantation has been shown to be a feasible, safe, and according to a number of recent reports, effective treatment for Parkinson's disease (PD). Fetal striatal transplantation may be as feasible, safe, and effective a treatment for Huntington's disease (HD), a disorder for which there is currently no effective treatment. This report describes our experience with fetal striatal transplantation to adult striatum in three HD patients. Three moderately advanced, nondemented HD patients received transplantation of fetal striatal tissue. The striatal precursor was selectively obtained from the lateral ganglionic eminence. Each patient received bilateral grafts from five to eight donors, placed into the caudate nucleus (one graft on each side) and the putamen (four grafts on each side). All three patients had HD as documented by family history, DNA heterozygosity (17-20 and 48-51 repeats), magnetic resonance imaging (MRI) revealing striatal atrophy, and 2-deoxyglucose positron emission tomography revealing striatal hypometabolism. All patients had been evaluated using the Unified Huntington's Disease Rating Scale and appropriate neuropsychological tests for at least 3 months prior to transplantation. One year following transplantation, MRI of all three patients revealed that the grafts survived and grew within the striatum without displacing the surrounding tissue. No patients demonstrated adverse effects of the surgery or the associated cyclosporin immunosuppression, nor did any patient exhibit deterioration following the procedure. The limited experience provided by these three patients indicates that fetal tissue transplantation can be performed in HD patients without unexpected complications.


Subject(s)
Corpus Striatum/embryology , Corpus Striatum/surgery , Fetal Tissue Transplantation , Huntington Disease/surgery , Adult , Brain/pathology , Humans , Huntington Disease/diagnosis , Huntington Disease/physiopathology , Magnetic Resonance Imaging , Male , Nervous System/physiopathology , Neuropsychological Tests , Postoperative Period
5.
Cell Transplant ; 6(3): 203-12, 1997.
Article in English | MEDLINE | ID: mdl-9171153

ABSTRACT

Neurotransplantation has been proposed as a potential treatment for the neurodegenerative disorder of Huntington's disease (HD), which currently has no effective therapy. While patients with Parkinson's disease have received neurotransplantation, until recently no HD patients have undergone transplantation for HD with standardized evaluations of their progress following surgery. The current report presents the cognitive changes in three patients with HD who underwent bilateral transplantation of human fetal striatal tissue. As part of the pre- and postsurgical evaluation, all three patients were administered a neuropsychological battery sensitive to the cognitive effects of HD within 2 mo prior to surgery and at 4-6 mo following transplantation. Four to 6 mo subsequent to surgery, all patients demonstrated increased scores on some measures of cognitive functioning. However, the pattern of changes was not uniform across subjects. These findings suggest that fetal striatal transplantation may improve some of the cognitive symptoms associated with HD in the three reported patients.


Subject(s)
Brain Tissue Transplantation , Corpus Striatum/transplantation , Fetal Tissue Transplantation , Huntington Disease/surgery , Adult , Attention , Humans , Huntington Disease/diagnosis , Learning , Magnetic Resonance Imaging , Male , Memory , Middle Aged , Neuropsychological Tests , Treatment Outcome
6.
J Comp Neurol ; 363(3): 377-88, 1995 Dec 18.
Article in English | MEDLINE | ID: mdl-8847406

ABSTRACT

Although central neurons do not naturally recover following injury, damaged adult septal neurons can regenerate when nerve growth factor (NGF) is provided along with a suitable cellular substrate. This study investigates the outgrowth of axotomized septal neurons grafted with primary fibroblasts genetically modified to produce NGF. Confocal microscope images of double staining for neuritic markers (neurofilament or low-affinity NGF receptor) and the astrocytic marker glial fibrillary acidic protein (GFAP) demonstrated that regenerating neurites crossed dense buildups of astrocytic processes at the edges of NGF-producing grafts and were in apposition with astrocytic processes within NGF-producing grafts. Immunoreactivity for acetylcholinesterase and low-(p75) and high-affinity (TrkA) NGF receptors was dense in NGF-producing grafts but absent in control grafts. NGF-grafted rats exhibited significantly increased hippocampal density of p75-immunoreactive fibers and significantly decreased ectopic hippocampal sympathetic ingrowth as compared to control-grafted rats. Rats with unilateral fimbria-fornix lesions and NGF-producing grafts exhibited ameliorated performance on a simple memory task. These findings demonstrate that implantation of NGF-producing grafts to the lesion cavity allows axotomized septal cholinergic neurons to reinnervate the hippocampus, and that rats receiving these grafts show a partial recovery of function.


Subject(s)
Axons/physiology , Hippocampus/physiology , Nerve Regeneration/physiology , Neurons, Afferent/physiology , Animals , Brain Tissue Transplantation/physiology , Cell Transplantation/physiology , Denervation , Female , Fibroblasts/physiology , Hippocampus/anatomy & histology , Hippocampus/cytology , Immunohistochemistry , Maze Learning/physiology , Mice , Microscopy, Confocal , Motor Activity/physiology , Nerve Growth Factors/biosynthesis , Rats , Rats, Inbred F344 , Sympathetic Nervous System/cytology , Sympathetic Nervous System/growth & development
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