Sarcomatoid anaplastic carcinoma of the small bowel in cardiac transplant bearer

Sarcomatoid carcinoma is a rare form of primitive carcinoma of the small bowel; it is considered a variant of adenocarcinoma, histologically characterized by a typical biphasic pattern with epithelial- and mesenchymal-like cells. Twenty-one cases have been described in the literature, presenting as small bowel obstructions (twenty cases) or superior vena cava syndrome (one case). The authors report the case of a 56 year-old man on immunosuppressive therapy for a heart transplant, who underwent surgery after a history of repeated episodes of melena, anemization and bowel obstruction. The operation brought to light an intraluminal occlusive mass in the distal ileum, associated with other intraluminal neoplasms of different sizes throughout the small bowel. No evidence of mesenteric adenopathies or hepatic metastases were found. Histological examination and immunohistochemical stain showed an anaplastic sarcomatoid carcinoma. The tumor cells showed strong positivity for cytokeratin and vimentin, and negativity for CD117 and CD34, as well as for all other characteristic markers of mesenchymal tumors. Early diagnosis is usually very difficult, due to the lack of any stereotyped clinical expression and the difficult to study the small bowel. Small-bowel barium follow-through or video capsule endoscopy can be helpful. In most cases, an emergency surgical operation is performed without a clear preoperative diagnosis. The case report is completed by a review of the literature.     

1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines: a series of potent and selective dopamine D(3) receptor antagonists

The discovery of new highly potent and selective dopamine D3 receptor antagonists has recently permitted characterization of the role of the dopamine D3 receptor in a wide range of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine-seeking behavior in the rat, reduces oral operant alcohol self-administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain.     

An update on targeted therapy in metastatic renal cell carcinoma

An improved understanding of the biological pathways deregulated in renal cell carcinoma has led to the development of various targeted agents, changing dramatically the therapeutic options for this disease. However, despite numerous opinions and guidelines, the optimal treatment still remains uncertain. In this review, we analyze the most recent published reports regarding the agents sunitinib, bevacizumab, sorafenib, temsirolimus, and everolimus. Moreover, we assess the novel targeted drugs pazopanib and axitinib. In addition, given the likely lack of cross-resistance between these targeting agents, we discuss sequential and combination targeted therapy in metastatic renal cell carcinoma, analyzing the most recent data.     

The emergence of Y-chromosome haplogroup J1e among Arabic-speaking populations

Haplogroup J1 is a prevalent Y-chromosome lineage within the Near East. We report the frequency and YSTR diversity data for its major sub-clade (J1e). The overall expansion time estimated from 453 chromosomes is 10 000 years. Moreover, the previously described J1 (DYS388=13) chromosomes, frequently found in the Caucasus and eastern Anatolian populations, were ancestral to J1e and displayed an expansion time of 9000 years. For J1e, the Zagros/Taurus mountain region displays the highest haplotype diversity, although the J1e frequency increases toward the peripheral Arabian Peninsula. The southerly pattern of decreasing expansion time estimates is consistent with the serial drift and founder effect processes. The first such migration is predicted to have occurred at the onset of the Neolithic, and accordingly J1e parallels the establishment of rain-fed agriculture and semi-nomadic herders throughout the Fertile Crescent. Subsequently, J1e lineages might have been involved in episodes of the expansion of pastoralists into arid habitats coinciding with the spread of Arabic and other Semitic-speaking populations.     

Psychophysiological reactivity,depression, neuroticism and type a behaviour: An interactive effect?

The greater reactivity in Type A subjects is a controversial issue. It is possible that anxiety, neuroticism and depression interact with Type A behaviour pattern, giving rise to different psychophysiological reactivity. To evaluate this hypothesis we studied 70 Italian healthy male volunteers. All were blue-collar workers. Cardiac health was confirmed by a detailed family and medical history. Individual assessment included the Structured Interview, the Eysenck Personality Questionnaire (EPQ), the State-Trait Anxiety Inventory (STAI) and the Depression Questionnaire (QD). To assess cardiac (rate-pressure product) and electrodermic (skin conductance level) psychophysiological reactivity we used the following tasks: (1) Interactive Concentration Test (ICT); (2) Mental Arithmetic (MAT); (3) Workside Noises (WN). In Type A (A1 + A2) subjects a higher neuroticism score was associated with greater reactivity whereas in non A (X + B) subjects a lower neuroticism score was associated with greater reactivity. Subjects classified as Type A with lower depression scores had greater cardiovascular responses, whereas in non A subjects higher depression scores were associated with greater reactivity.     

Prophylactic oophorectomy: a historical perspective

Removal of a woman's ovaries (known as bilateral oophorectomy, ovariectomy or, historically, ovariotomy) is undertaken in a number of countries. An estimated 19,000 women aged <60 years had a bilateral prophylactic oophorectomy in the UK in 2003, either as a planned response to an increased specific genetic risk of ovarian or breast cancer or, more frequently, as a prophylactic measure to prevent ovarian cancer. Despite its popularity, however, a full evaluation of the risks, costs and benefits of prophylactic oophorectomy in the absence of genetic markers and at the time of hysterectomy has not yet been undertaken. This paper seeks to provide a historical perspective on current practice by outlining approaches to the ovary in Britain from the 19th century onwards. Historically, ovarian removal has raised many questions about the costs and benefits of surgery. The aim of this article is to highlight the issues, and in so doing, to contribute to a more informed assessment of current practice.     

HbF reactivation in sibling BFU-E colonies: synergistic interaction of kit ligand with low-dose dexamethasone

Mechanisms underlying fetal hemoglobin (HbF) reactivation in stress erythropoiesis have not been fully elucidated. We suggested that a key role is played by kit ligand (KL). Because glucocorticoids (GCs) mediate stress erythropoiesis, we explored their capacity to potentiate the stimulatory effect of KL on HbF reactivation, as evaluated in unilineage erythropoietic culture of purified adult progenitors (erythroid burst-forming units [BFU-Es]). The GC derivative dexamethasone (Dex) was tested in minibulk cultures at graded dosages within the therapeutical range (10(-6) to 10(-9) M). Dex did not exert significant effects alone, but synergistically it potentiated the action of KL in a dose-dependent fashion. Specifically, Dex induced delayed erythroid maturation coupled with a 2-log increased number of generated erythroblasts and enhanced HbF synthesis up to 85% F cells and 55% gamma-globin content at terminal maturation (ie, in more than 80%-90% mature erythroblasts). Equivalent results were obtained in unicellular erythroid cultures of sibling BFU-Es treated with KL alone or combined with graded amounts of Dex. These results indicate that the stimulatory effect of KL + Dex is related to the modulation of gamma-globin expression rather than to recruitment of BFU-Es with elevated HbF synthetic potential. At the molecular level, Id2 expression is totally suppressed in control erythroid culture but is sustained in KL + Dex culture. Hypothetically, Id2 may mediate the expansion of early erythroid cells, which correlates with HbF reactivation. These studies indicate that GCs play an important role in HbF reactivation. Because Dex acts at dosages used in immunologic disease therapy, KL + Dex administration may be considered to develop preclinical models for beta-hemoglobinopathy treatment.     

SECT and MAST: new tests to assess grammatical abilities in primary progressive aphasia

Background: The presence/absence of agrammatism is critical for the classification of the different subtypes of primary progressive aphasia (PPA). Its quantitative evaluation is, however, a challenge in clinical practice because there are few brief, reliable, and easy-to-administer tests. Linguistic analysis of connected speech is the gold standard but is impractical outside the research setting.

Aims: To tackle the need for brief grammatical tests, we developed the SEntence Comprehension Test (with auditory and visual versions, SECT A and V) and the Make A Sentence Test (MAST).

Methods & Procedures: The tests were given to 92 participants (41 PPA patients, 21 Alzheimer’s disease patients, and 30 controls) from the Cambridge Longitudinal Study of PPA. Classification of the different subtypes of PPA was made purely on clinical assessment to avoid circularity from using the tests for diagnostic purposes. In addition, speech samples were recorded during a face-to-face semi-structured interview and all participants completed a standard neuropsychological battery as well as the three new tests.

Outcomes & Results: All patients were impaired relative to controls on the SECT A and V. After controlling for semantic impairment, only the mixed variant of PPA (mPPA) and the non-fluent variant of PPA were impaired on the MAST. When controlling for working memory in SECT A, the mPPA only remained impaired. Regression analyses demonstrated that performance on the SECT A and V, and the MAST, was strongly related to measures of the patients’ spontaneous speech, particularly the number of grammatical errors and the percentage of abandoned and elliptical sentences. Performance on the SECT A was also significantly predicted by speech rate.

Conclusion: The SECT and the MAST are brief tests capable of reflecting grammatical difficulty in spontaneous speech.