Glial cell-line derived neurotrophic factor (GDNF) is a potent survival factor for embryonic midbrain dopaminergic, spinal motor, cranial sensory, sympathetic, and hindbrain noradrenergic neurons, and is available to these cells in vivo. It is therefore considered a physiological trophic factor and a potential therapeutic agent for Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. Here we show that at postnatal day 0 (P0), GDNF-deficient mice have deficits in dorsal root ganglion, sympathetic and nodose neurons, but not in hindbrain noradrenergic or midbrain dopaminergic neurons. These mice completely lack the enteric nervous system (ENS), ureters and kidneys. Thus GDNF is important for the development and/or survival of enteric, sympathetic and sensory neurons and the renal system, but is not essential for catecholaminergic neurons in the central nervous system (CNS).

There are many conflicting results in the literature comparing quality of life following breast-conserving therapy (BCT) and mastectomy. This study compared long-term quality of life between breast cancer patients treated by BCT or mastectomy in three age groups. Patients (n = 990) completed a quality of life survey, including the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), at regular intervals over 5 years. In the cross-sectional data, mastectomy patients had significantly (p < 0.01) lower body image, role, and sexual functioning scores and their lives were more disrupted than BCT patients. Emotional and social functioning and financial and future health worries were significantly (p < 0.01) worse for younger patients. There were no differences in body image and lifestyle scores between age groups. There was also no interaction between age and surgery method. Even patients > or =70 years of age reported higher body image and lifestyle scores when treated with BCT. The repeated measures analysis indicated that four functioning scores, half the symptom scores, future health, and global quality of life improved significantly (p < 0.01) over time. All these variables increased significantly for BCT patients and those 50 to 69 years of age. Body image, sexual functioning, and lifestyle disruption scores did not improve over time. BCT should be encouraged in all age groups. Coping with appearance change should be addressed in patient interventions.

Anterior resection and nonstoma patients, despite suffering micturition and defecation problems, had better quality of life scores than abdominoperineal extirpation and stoma patients. Comparisons between abdominoperineal extirpation and anterior resection patients should consider the effect of temporary stomas. Improvements in quality of life scores over time may be explained by reversal of temporary stomas or physiologic adaptation.

Glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor j33 Parkinson disease is one of the most common neurological disorders of the elderly. It is characterized by a progressive degeneration of the dopaminergic neurons in the substantia nigra of the midbrain, leading to a loss of dopamine in the striatum, which constitutes the main projection field of these cells. Although therapeutically relevant augmentation of striatal dopamine can be achieved by drug therapy or intrastriatal transplantation of fetal dopaminergic neurons (1), there is at present no means by which the primary nigral degeneration can be halted. Neurotrophic factors capable of sustaining the survival of otherwise degenerating dopamine neurons are thus of considerable interest (2). GDNF was initially purified and cloned as a potent neurotrophic factor for cultured dopaminergic neurons of the developing substantia nigra (3), and it has been shown that the related transforming growth factors 32 and ,B3 (TGF-f32 and TGF-f33) exert a similar survival-promoting activity on this cell population in vitro (4-6). The expression patterns of GDNF, TGF-j32, and TGF-,B3 mRNAs in the developing rat striatum and substantia nigra further support the notion that one or several of these factors play important physiological roles for immature nigral dopamine neurons (4, 7-9). More recently, administration of GDNF to the basal ganglia has been shown to partially attenuate the disappearance of tyrosine hydroxylase (TH)-immunoreactive nigral neurons following surgical axotomy (10) and the acute toxic effects of systemic doses of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in adult mice (11) or of intracerebral 6-hydroxydopamine (6-OHDA) in rats (12).The aim of the present study was (i) to investigate whether GDNF would exert a protective effect in a model of delayed and progressive nigral cell death more closely related to the cell death seen in human Parkinson disease and (ii) to compare GDNF and the related TGF-f33 with respect to their capacity to counteract nigral dopamine cell degeneration in the adult rat brain.To do so, we used a recent modification of the standard 6-OHDA lesion of the rat nigrostriatal projection (13-15). Unilateral 6-OHDA-lesioning of the dopaminergic terminals in the striatum rather than the medial forebrain bundle or the substantia nigra itself produces a delayed and progressive degeneration of ipsilateral nigral dopamine neurons with an onset 1 week after 6-OHDA injection (15). One week prior to striatal 6-OHDA lesion, nigral cells were retrogradely labeled at the site of subsequent striatal toxin injection with the fluorescent retrograde tracer fluorogold. This allows a specific examination of those nigrostriatal neurons projecting to, or through, the focus of the 6-OHDA lesion. For within-animal controls, fluorogold injections were performed bilaterally, and only one of the labeled striata was subsequently lesioned with 6-OHDA. into both striata at sites 1 mm anterior to bregma and 3 mm later...

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Glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neuroprotective effects on dopamine (DA) neurons in vivo. Here we report long-term rescue of nigral DA neurons after delayed short-term GDNF administration in a rat lesion model that reproduces the slowly progressing degenerative process seen in Parkinson's disease. GDNF injected close to the substantia nigra provided near-complete protection and persistent survival of the lesioned nigral neurons for at least 4 months after discontinuation of GDNF treatment. Long-term rescue of the nigral cells, however, was not accompanied by any significant reinnervation of the lesioned striatal target or any signs of functional recovery in either drug-induced or spontaneous motor behaviors. We conclude that not only preservation of the nigral DA neurons but also restoration of striatal DA function is necessary for functional recovery in the rat Parkinson model.

Research has indicated that several demographic and clinical factors may affect the quality of life of breast cancer patients. Few studies, however, have sufficient sample sizes for multivariate analyses to be tested. Furthermore, several important factors, such as arm morbidity, communication and comorbid illness, have not been included in quality of life models The aim of this study was to predict the simultaneous effect of these factors on long-term quality of life. Breast cancer patients (n = 990) completed a quality of life survey, including the EORTC QLQ-C30, over five years. Clinical details were registered in the Munich Cancer Registry. Eleven predictors across eight quality of life domains were analyzed over a period of five years using a logistic regression model. Arm problems, communication, comorbidity, age, surgery. and, to a lesser extent, marital, educational and employment status were significantly associated with quality of life. Adjuvant therapy, medical insurance and pT category were not significant predictors. This study is the first to demonstrate the consistency and strength of arm dysfunction and doctor-patient communication on breast cancer patients' quality of life. These important factors in breast cancer care can be improved and should be regarded as a priority.

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