Rapp-Hodgkin Syndrome with Pili Canaliculi

Abstract: A 20-year-old woman and her 12-year-old brother had hypohidrotic ectodermal dysplasia, cleft lip and palate, midfacial hypoplasia with narrow nose from the nasal bridge to the tip, narrow dysplastic nails, and conical teeth and hypodontia, and hypospadias and hypoplastic uvula in the boy. The woman had major underdevelopment of intellectual capacity. The most important hair anomalies in both siblings were sparse eyebrows, pili torti, and pili canaliculi. Some of the pili canaliculi had two canals (pili bicanaliculi), and the cross section for scanning electron microscopy had a quadrangular aspect. This is the seventh family reported with Rapp-Hodgkin ectodermal dysplasia.     

Acute myocardial infarction after blunt chest trauma in young people: Need for prompt intervention

We describe four cases of acute myocardial infarction in young patients, secondary to blunt chest trauma. One case was treated with intracoronary thrombolysls and angioplasty, two cases received systemic thrombolysis, and the last one did not have any reperfusion therapy. The coronary angiograms of the left anterior descending artery showed thrombosis in two cases, coronary dissection in one case, and no morphological lesions in the other. We encourage the early performance of angiographic studies in these patients, adjusting the therapy to their pathophysiologic mechanism.     

The phosphatase PRL-3 affects intestinal homeostasis by altering the crypt cell composition

Expression of the phosphatase of regenerating liver-3 (PRL-3) is known to promote tumor growth in gastrointestinal adenocarcinomas, and the incidence of tumor formation upon inflammatory events correlates with PRL-3 levels in mouse models. These carcinomas and their onset are associated with the impairment of intestinal cell homeostasis, which is regulated by a balanced number of Paneth cells and Lgr5 expressing intestinal stem cells (Lgr5+ ISCs). Nevertheless, the consequences of PRL-3 overexpression on cellular homeostasis and ISC fitness in vivo are unexplored. Here, we employ a doxycycline-inducible PRL-3 mouse strain to show that aberrant PRL-3 expression within a non-cancerous background leads to the death of Lgr5+ ISCs and to Paneth cell expansion. A higher dose of PRL-3, resulting from homozygous expression, led to mice dying early. A primary 3D intestinal culture model obtained from these mice confirmed the loss of Lgr5+ ISCs upon PRL-3 expression. The impaired intestinal organoid formation was rescued by a PRL inhibitor, providing a functional link to the observed phenotypes. These results demonstrate that elevated PRL-3 phosphatase activity in healthy intestinal epithelium impairs intestinal cell homeostasis, which correlates this cellular mechanism of tumor onset with PRL-3-mediated higher susceptibility to tumor formation upon inflammatory or mutational events.

Key messages

? Transgenic mice homozygous for PRL-3 overexpression die early.

? PRL-3 heterozygous mice display disrupted intestinal self-renewal capacity.

? PRL-3 overexpression alone does not induce tumorigenesis in the mouse intestine.

? PRL-3 activity leads to the death of Lgr5+ ISCs and Paneth cell expansion.

? Impairment of cell homeostasis correlates PRL-3 action with tumor onset mechanisms.

     

Intestinal IFN-γ production is associated with protection from clinical signs,but not with elimination of worms,in Echinostoma caproni infected-mice

In the present paper, we assess the relationship between the expression of IFN-γ and the development of clinical signs in Echinostoma caproni-infected mice. For this purpose, we studied the course of the infection in three mouse strains: ICR (CD-1®) (a host of high compatibility with E. caproni), BALB/c (a prototypical Th2 strain), and BALB/c deficient for IFN-γ mice (IFN-γ^?/?). Infection in ICR mice is characterized by the elevated expression of IFN-γ and iNOS in the intestine concomitantly with the lack of clinical signs. In contrast, the infection was more virulent in BALB/c and IFN-γ-deficient mice that developed a severe form of the disease together with the absence of IFN-γ expression. The disease was more severe in IFNγ^?/? mice in which the disease was lethal during the few first weeks of the infection. The analysis of different parameters of the infection in each host strain showed that most of the features were similar in the three mouse strains, suggesting the IFN-γ plays a central role in that protection against severe disease. Thus, IFN-γ seems to play a dichotomous role in the infection facilitating the parasite establishment, but it may also benefit mice since it protects the mice from morbidity and mortality induced by the parasite.     

Retrospective study of tolerance to short initiation schedules in subcutaneous immunotherapy.

With the aim of evaluating tolerance to new shorter initiation schedules in subcutaneous immunotherapy everyday clinical practice, a study was carried out using Pangramin Plus with initiation periods between 3 (Cluster) and 6 (Plus) weeks. All the information was processed retrospectively and both systemic (SR) and local (LR) adverse reactions occurring between September 2002 and February 2003 were recorded. A total of 353 patients (261 Plus and 91 Cluster) were included and 2,886 doses were administered (2,166 in initiation and 720 in maintenance). Of these, 800 were with Grass mix extract, 1,141 Grass mix + Olea, 273 Olea, 73 Dermatophagoides mix and 599 Dermatophagoides pteronyssinus. As regards adverse reactions (AR), 2.8% of patients showed SR and 4.8% LR, 1.2% of doses caused some type of reaction (SR and LR in 0.3% and 0.9%, respectively). The initiation schedule, first dose or allergens resulted in no significant differences in the frequency of adverse reactions. The Grass mix extract showed the highest frequency of AR. Sixty-seven percent of SR and 68% of LR were delayed. 64% of these reactions resolved spontaneously while the rest responded favourably to treatment. Adrenaline was administered on one occasion for immediate asthma. There were no cases of anaphylactic shock, hospitalisation or life-threatening situations. Pangramin Plus tolerance, therefore, can be classified as good, similar to conventional schedules, but with the benefits of shorter initiation schedules.     

Neural activity associated with metaphor comprehension: spatial analysis

Though neuropsychological data indicate that the right hemisphere (RH) plays a major role in metaphor processing, other studies suggest that, at least during some phases of this processing, a RH advantage may not exist. The present study explores, through a temporally agile neural signal--the event-related potentials (ERPs)--, and through source-localization algorithms applied to ERP recordings, whether the crucial phase of metaphor comprehension presents or not a RH advantage. Participants (n=24) were submitted to a S1-S2 experimental paradigm. S1 consisted of visually presented metaphoric sentences (e.g., "Green lung of the city"), followed by S2, which consisted of words that could (i.e., "Park") or could not (i.e., "Semaphore") be defined by S1. ERPs elicited by S2 were analyzed using temporal principal component analysis (tPCA) and source-localization algorithms. These analyses revealed that metaphorically related S2 words showed significantly higher N400 amplitudes than non-related S2 words. Source-localization algorithms showed differential activity between the two S2 conditions in the right middle/superior temporal areas. These results support the existence of an important RH contribution to (at least) one phase of metaphor processing and, furthermore, implicate the temporal cortex with respect to that contribution.     

Analysis of polymorphisms of the vitamin D receptor, estrogen receptor, and collagen Ialpha1 genes and their relationship with height in children with bone cancer

PURPOSE: The authors' objectives were to compare height at diagnosis of children with bone tumors with that of Spanish reference children; to analyze the frequency of the genotypes for the polymorphisms of the vitamin D receptor (VDR), estrogen receptor (ER), and collagen Ialpha1 (COLIalpha1) genes in patients and in healthy controls; and to test the relationship between the genetic markers and height. PATIENTS AND METHODS: Height and weight at diagnosis were measured in 58 osteosarcoma and 36 Ewing sarcoma patients and compared with standards published for Spanish reference children according to sex and age. For the molecular analysis, genetic polymorphisms of the VDR (Fok I, Apa I, and TaqI), ER (Pvu II and XbaI), and COLIalpha1 (Msc I) genes were characterized in 72 osteosarcoma and 53 Ewing sarcomas and in a group of 143 healthy matched children. RESULTS: Osteosarcoma and Ewing sarcoma patients were significantly taller than Spanish reference children. Osteosarcoma patients showed a significantly higher frequency of the Ff genotype for the Fok I polymorphism (VDR gene) than the control group. The odds ratio for this genotype was 1.78, with an increased relative risk of 78% for heterozygous Ff carriers. Among Ewing sarcoma patients, this same genotype was significantly associated with lower height than homozygotes (FF or ff). CONCLUSIONS: Children with bone cancer are significantly taller than the reference population, which may be influenced by the genotype for the Fok I polymorphism of the VDR gene.     

Body composition assessed by anthropometry and bioelectric impedance analysis in older persons recovering from cerebrovascular accident

We investigated body composition in older patients who had experienced a cerebrovascular accident (CVA) and were participating in a recovery program that included physical exercise. We studied 61 persons in two groups. One group consisted of 13 men and 12 women (mean age, 68 years) who were receiving day center care to recover from a CVA that had occurred from six months to one year previously. The second group (control) consisted of 20 men and 16 women (mean age, 68 years) in good health, residing in a retirement home. Most subjects in both groups were able to perform normal activities of daily living without help and showed a high degree of independence (> 60 on the Barthel scale). Bioelectric impedance and anthropometric methods were used to measure the magnitude of changes in fat-free mass and fat mass. Percentage total body fat measured with bioelectric impedance was higher in both groups than when measured anthropometrically. The anthropometric values and bioelectric impedance results in patients who participated in a physical exercise program were similar to the findings in control subjects. The anticipated loss in muscle mass and gain in body fat as a result of inactivity associated with illness was not seen, possibly because of the personalized program of continuous physical exercise. Our comparison of older people recovering from CVA and apparently healthy older people illustrates the benefits of physical exercise in compensating for changes in body composition as a result of immobility during convalescence.     

Alprazolam compared to clobazam and placebo in anxious outpatients

In this double-blind study we compared alprazolam, clobazam, and placebo for the treatment of outpatients suffering from generalized anxiety disorder. At the end of the treatment, the three groups were significantly improved without showing differences among them. However, both active-drug groups were much improved at the end of week 1 in contrast to the placebo group. We were unable to find any difference on efficacy evaluations between alprazolam and clobazam, but alprazolam reached a consistently better outcome on some ratings compared to placebo. Although benzodiazepines share many common properties, it is necessary to identify selected groups of patients that can be helped by specific compounds or even placebo.