On the classification of the acrocephalosyndactyly syndromes

This report describes a family in which two different types of acrocephalosyndactyly (ACS) were clinically identified. The proband presented with the classic stigmata of Pfeiffer syndrome, while her cousin was considered to be a typical case of Apert syndrome. Seven other family members also have unusually shaped heads and the facial appearance reminiscent of Crouzon disease.
Observations made in this family and from previous reports in the literature, we feel there is substantial reason to re-evaluate the ACS classification and to consider that the Apert and Pfeiffer types of ACS may be one and the same.     

Two new mutations and three novel polymorphisms in the<Emphasis Type="Italic"> RB1</Emphasis> gene in Ecuadorian patients

RB1 is the gene responsible for retinoblastoma, the most common malignant intraocular tumor of infancy and early childhood. There are no reports about this gene in Ecuadorian populations, and only a few studies have been published in Latin America about this subject. There is a spectrum of more than 370 mutations described in the RB1 gene mutation database (http://www.d-lohmann.de/Rb/mutations.html), and alterations have been found in 25 of the 27 exons. During the exon-by-exon analysis of 31 tumor and blood samples from Ecuadorian patients, we found two new mutations and three novel polymorphisms. One of the polymorphisms is located in intron 26 where no alterations of the gene have been described previously. The polymorphisms were found in all of the patients tumor samples, but not in normal population, suggesting there might be a relationship between these polymorphisms and the development of retinoblastoma in the Ecuadorian population.The nucleotide sequence data reported are available in the GenBank database under the accession numbers: AY243567, AY260472, AY260473, AY273783     

Entrainment by a palatable meal induces food-anticipatory activity and c-Fos expression in reward-related areas of the brain

Rats maintained under restricted feeding schedules (RFS) develop food-anticipatory activity and entrainment of physiological parameters. Food entrainment is independent of the suprachiasmatic nucleus and depends on food-entrainable oscillators (FEO). Restricted feeding schedules lead animals toward a catabolic state and to increase their food driven motivation, suggesting that in this process metabolic- and reward-related mechanisms are implicated. This study explored if motivation driven by a palatable meal is sufficient to produce food-entrainment. To address this question, we evaluated whether daily fixed access to a highly palatable meal entrained (PME) locomotor activity, serum glucose and free fatty acids concentrations in rats maintained without food deprivation. The entrained response of PME rats was compared with rats entrained to RFS. In a second experiment, we used c-Fos-IR to identify structures in the central nervous system involved with PME. Rats showed anticipatory activity to a daily palatable meal, with a lower intensity than rats entrained to RFS. Anticipatory activity persisted at least for four cycles after interrupting palatable meal, suggesting that this persistence depends on an endogenous oscillator. Glucose and free fatty acids were not entrained in PME rats. c-Fos expression in limbic system nuclei was in phase with PME time, but not in the hypothalamus. Results suggest 1) that food deprivation, i.e. a catabolic state is not necessary for the expression of anticipatory activity; 2) that an increase in the motivational state due to taste and/or nutritional contents of palatable meal is sufficient to entrain behavior; and 3) that structures in the limbic system are involved in this entrainment process. The present study indicates that metabolic and motivational mechanisms are involved in food entrainment, and suggests that the FEO may be a multi-oscillatory system distributed over different regulatory systems in the brain.     

Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol.

We report the results of reduced-intensity conditioning allogeneic stem cell transplantation (allo-RIC) in patients with advanced Hodgkin lymphoma (HL). Forty patients with relapsed or refractory HL were homogeneously treated with an RIC protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2) intravenously) and cyclosporin A and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Twenty-one patients (53%) had received >2 lines of chemotherapy, 23 patients (58%) had received radiotherapy, and 29 patients (73%) had experienced treatment failure with a previous autologous stem cell transplantation. Twenty patients (50%) were allografted in resistant relapse, and 38 patients received hematopoietic cells from an HLA-identical sibling. Five patients (12%) died from early transplant-related mortality (before day +100 after allo-RIC). One-year transplant-related mortality was 25%. Acute GVHD developed in 18 patients (45%). Chronic GVHD developed in 17 (45%) of the 31 evaluable patients. The response rate 3 months after the allo-RIC was 67% (21 [52%] complete remissions and 6 [15%] partial remissions). Eleven patients received donor lymphocyte infusions (DLIs) for disease relapse. The response rate after DLI was 54% (3 complete remissions and 3 partial remissions). Overall survival (OS) and progression-free survival (PFS) were 48% +/- 10% and 32% +/- 10% at 2 years, respectively. Refractoriness to chemotherapy was the only adverse prognostic factor for both OS (63% +/- 12% versus 35% +/- 13%; P = .05) and PFS (55% +/- 16% versus 10% +/- 9%; P = .006). For patients with failure of a prior autologous hematopoietic stem cell transplantation, results were especially good for those who experienced late relapses (>/=12 months: 2-year OS and PFS were 75% +/- 16% and 70% +/- 18%, respectively). These data suggest that allo-RIC is feasible in heavily pretreated HL patients and has an acceptable early transplant-related mortality. Results are better in patients allografted in sensitive disease. Both responses observed after the development of GVHD and DLI may suggest a graft-versus-HL effect. Allo-RIC has to be considered an effective therapeutic approach for patients who have had treatment failure with a previous autologous hematopoietic stem cell transplantation.     

Identification of 26 new constitutional RB1 gene mutations in Spanish, Colombian, and Cuban retinoblastoma patients

Constitutional mutations in the RB1 gene predispose to retinoblastoma development. Hence genetic screening of retinoblastoma patients and relatives is important for genetic counseling purposes. In addition, RB1 gene mutation studies may help decipher the molecular mechanisms leading to tumors with different degrees of penetrance or expressivity. In the course of genetically screening of 107 hereditary and non-hereditary retinoblastoma patients (11 familiar bilateral, 4 familiar unilateral, 49 sporadic bilateral and 43 sporadic unilateral) and kindred from Spain, Colombia and Cuba, using direct PCR sequencing, we observed 45 distinct mutations and four RB1 deletions in 53 patients (9 familiar bilateral, 2 familiar unilateral, 31 sporadic bilateral and 11 sporadic unilateral). Most of these mutations (26/45, 57%) have not been reported before. In 32 patients, the predisposing mutations correspond to nonsense (mainly CpG transitions) and small insertions or deletions whose expected outcome is a truncated Rb protein that lacks the functional pockets and tail. Five single aminoacid replacements and seventeen mutations affecting splicing sites were also observed in retinoblastoma patients. Two of these sixteen mutations are of unclear pathogenic nature.     

Predictors of health-related quality of life in Parkinson’s disease: the impact of overlap between health-related quality of life and clinical measures

Quality of Life Research - This study aimed to determine predictors of health-related quality of life (HRQoL) in Parkinson's disease (PD) and to explore their predictive value before and after...