Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer.

This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000 mg m(-2) bid on days 1-14 and oxaliplatin 130 mg m(-2) on day 1), followed by RT (1.8 Gy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825 mg m(-2) bid on days 22-35 and 43-56, and oxaliplatin 50 mg m(-2) on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13-36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer.

Una nueva hipótesis para el origen del déficit neuronal y las alteraciones de la diferenciación neuronal asociadas al síndrome de Down: implicación del gen Minibrain / A new hypothesis for the neuronal deficit and the alterations in neuronal differentiation associated to Down syndrome: implication of the Minibrain gene

La disminución de neuronas, diversos defectos en la diferenciación neuronal y la aparición de síntomas neurodegenerativos están entre las alteraciones neuropatológicas que hacen del síndrome de Down (SD) la causa más frecuente de retraso mental. El SD se debe a la triplicación del cromosoma 21. En base a estudios genéticos y a la secuenciación de este cromosoma se han podido identificar los genes posiblemente más relevantes para la generación del SD, entre los cuales destaca Minibrain (Mnb). Dos han sido los objetivos de este trabajo: estudiar si Mnb podría estar implicado en la diferenciación neuronal y ver si la sobreexpresión de Mnb tiene efectos sobre muerte neuronal. Paralelamente se han intentado ver la relaciones de estas funciones del gen Mnb con las neuropatologías asociadas al SD. Exoerimentos llevados a cabo en modelos exaerimentales transgi!nicos demuestran que la sobreexpresión de Mnb genera muerte neuronal. Asimismo. los estudios de exaresión de Mnb durante el desarrollo tardío del cerebro sugiere; un papel de las Mnb-quinasas como elemento de señalización celular en el proceso de diferenciación neuronal. Todo ello contribuye a confeccionar una nueva hipótesis sobre las bases moleculares del déficit neuronal y las alteraciones de la diferenciación neuronal que se producen en el SD (AU)

The decrease of neuronal number, diverse defects in neuronal differentiation, and neurodegeneration are among the neuropathologic alterations which make DS the most frequent cause of mental retardation. DS is originated by triplication of chromosome 21. Based on genetic studies and the sequencing of chromosome 21, the possible most relevant genes for DS generation have been identified. Among them Minibrain (Mnb) appears the most likely candidate to explain some DS neuropathologies. Our work has approached two objectives: to study if Mnb could be involved in neuronal differentiation and find out if the overexpression of Mnb has an effect on cell death. In parallel, we have tried to establish the correlation of these functions of Mnb with the DS associated neuropathologies. By using transgenic experimental models, we have found that overexpression of Mnb induces neuronal death. Also, the expression of Mnb during late brain development suggests a role of Mnb-kinases as an important signaling element within the process of neuronal differentiation. Al1 to~ether.t hese results contribute to build a new hypothesis for the molecular basis of the neuronal deficit and alterations of neuronal differentiation associated to DS (AU)

[Cost reduction in long-term nursing thanks to a memory clinic--results of a case control study]. / Kostenreduktion im Langzeitpflegebereich dank Memoryklinik--Resultate einer Fallkontrollstudie.

Between 1991 and 1995, 334 persons from the city of Zurich have been investigated at the gerontologic counselling facility of the memory clinic of the nursing home Entlisberg near Zurich. 49 (14.7%) of these persons suffered from a treatable disease (16 from depression, 13 from chronic intoxication, 20 from other treatable diseases), 10 from other disturbances (debility or postapoplectic state), and 275 from dementia. In 45% of the cases dementia was moderate, in 47% moderate to severe, and in 8% severe. In most cases dementia was of Alzheimer's type (60.7%), others were of multi-infarct type (17.5%), of mixed type (13.1%), or other types (8.7%). Until march 1996, 64 (19.4%) of these 334 on the average 74-year-old persons treated in the memory clinic have been admitted to a city nursing home. They have compared to a random sample, including 312 demented persons of similar ages and similar date of admittance to the same institutions. The proportion of demented persons cared before admittance by a spouse was about 28% in both groups. On an average, the mini mental state (Zurich variant) at admittance to a nursing home was 10.95 points in patients from the memory clinic, compared to 13.43 points in the control group. Thus, patients that have formerly been advised and trained entered the nursing home in a state of dementia more advanced by 2.48 points. Based on an average yearly demelioration by about 2.4 points, this means admittance to a nursing home is delayed by 376 days. Patients for whom admittance to a nursing home could be avoided completely by the treatment proposed by the counselling were not considered in this calculation.