Basaloid squamous carcinoma with a spindle cell component and osseous metaplasia presenting as a polyp of the hypopharynx

We report a case of basaloid squamous carcinoma with a spindle cell component of the hypopharynx, in a 61-years-old-man. An excisional biopsy of a pedonculated and polypoid tumour was performed by endoscopy. The histologic examination revealed a biphasic tumour with both a basaloid carcinomatous and a spindle cell component. Focally, osseous metaplasia was seen. The spindle cell component demonstrated immunoreactivity with the p63 epithelial marker. The patient was treated with chemotherapy followed by radiotherapy. The patient has been free of disease for one year. It's the ninth case reported in the literature of a biphasic carcinoma with both a basaloid squamous and a spindle cell component and the first case with osseous metaplasia.     

Role of environmental fluctuations and microbial diversity in degradation of hydrocarbons in contaminated sludge

Little is known about microbial communities involved in hydrocarbon degradation, whether it be their structural and functional diversity or their response to environmental constraints such as oxygen fluctuation. Here, current knowledge of the impact of diversity and redox oscillations upon ecosystem processes is reviewed. In addition, we present the main conclusions of our studies in this field. Oxic/anoxic oscillations had a strong impact upon bacterial community structures, influencing their ability to degrade hydrocarbons and their capacity to reduce hydrocarbon toxicity. Furthermore, a decrease in functional diversity has a strong impact on pollutant degradation.     

Ghrelin/obestatin ratio in two populations with low bodyweight: constitutional thinness and anorexia nervosa

Constitutional thinness (CT) and anorexia nervosa (AN) are two categories of severely underweight subjects. Some appetite-regulating hormones display opposite levels in AN and CT. While levels of ghrelin, an orexigenic hormone, fit with the normal food intake in CT, the lack of efficacy of increased ghrelin levels in AN is not clear. Obestatin is a recently described peptide derived from the preproghrelin gene, reported to inhibit appetite in contrast to ghrelin. The aim of this study was to determine whether the circadian profile of obestatin, total and acylated ghrelin levels is different in CT subjects when compared with AN patients. Six-points circadian profiles of plasma obestatin, acylated ghrelin, total ghrelin and other hormonal and nutritional parameters were evaluated in four groups of young women: 10 CT, 15 restricting-type AN, 7 restored from AN and 9 control subjects. Obestatin circadian levels were significantly higher in AN (p<0.0001) while no difference was found between CT and control subjects. Acylated and total ghrelin were found increased in AN. Acylated ghrelin/obestatin and total ghrelin/obestatin were found decreased in AN compared to CT or C subjects (p<0.05). The percentage of acylated ghrelin was found decreased in CT group (p<0.05). The decreased ghrelin/obestatin ratio found in AN might participate in the restraint in nutriment intake of these patients. In contrast, in CT a lower percentage of acylated over total ghrelin might be considered in the aetiology of this condition.     

Comparative study of complete versus incomplete Kawasaki disease in 59 pediatric patients

ObjectivesTo compare the clinical and laboratory features and the rate of echocardiographic coronary artery abnormalities in patients with complete and incomplete forms of Kawasaki disease (KD) and to determine which additional clinical criteria might support a suspicion of KD.MethodsWe retrospectively reviewed the medical records of patients with KD who were admitted to the general pediatrics department of the Kremlin Bicêtre Teaching Hospital, France, between January 1995 and May 2006. We compared patients with a fever and four or five of the principal criteria (complete KD) to the other patients (incomplete KD). Clinical and laboratory features were abstracted from the records.ResultsWe identified 63 patients with a mean age of 33 months (± 31). The male-to-female ratio was 2.47. Four patients were excluded. Of the remaining 59 patients, 39 had complete KD and 20 incomplete KD. The group with complete KD had significantly higher rates of changes in the extremities, conjunctival injection, exanthem, and enanthem; and a significantly lower rate of coronary artery dilation (48.7% vs. 90% in the incomplete KD group, P = 0.002). Serum levels of alanine aminotransferase and gamma glutamyl transferase were significantly higher in the complete KD group. No significant differences were found between the two groups regarding age, sex, blood cell counts, or laboratory markers for inflammation. Pyuria was found in 45.4% of patients with complete KD and in 30.8% of those with incomplete KD (P = 0.17). Of 14 patients who underwent ophthalmological evaluation, two had uveitis; both of them had complete KD.ConclusionIncomplete KD shares with complete KD a risk of coronary artery disease. The diagnosis of incomplete KD is challenging but can be supported by the presence of features other than the principal criteria, such as acute anterior uveitis or unexplained pyuria.     

Decreased basal fMRI functional connectivity in epileptogenic networks and contralateral compensatory mechanisms

A better understanding of interstructure relationship sustaining drug-resistant epileptogenic networks is crucial for surgical perspective and to better understand the consequences of epileptic processes on cognitive functions. We used resting-state fMRI to study basal functional connectivity within temporal lobes in medial temporal lobe epilepsy (MTLE) during interictal period. Two hundred consecutive single-shot GE-EPI acquisitions were acquired in 37 right-handed subjects (26 controls, eight patients presenting with left and three patients with right MTLE). For each hemisphere, normalized correlation coefficients were computed between pairs of time-course signals extracted from five regions involved in MTLE epileptogenic networks (Brodmann area 38, amygdala, entorhinal cortex (EC), anterior hippocampus (AntHip), and posterior hippocampus (PostHip)). In controls, an asymmetry was present with a global higher connectivity in the left temporal lobe. Relative to controls, the left MTLE group showed disruption of the left EC-AntHip link, and a trend of decreased connectivity of the left AntHip-PostHip link. In contrast, a trend of increased connectivity of the right AntHip-PostHip link was observed and was positively correlated to memory performance. At the individual level, seven out of the eight left MTLE patients showed decreased or disrupted functional connectivity. In this group, four patients with left TLE showed increased basal functional connectivity restricted to the right temporal lobe spared by seizures onset. A reverse pattern was observed at the individual level for patients with right TLE. This is the first demonstration of decreased basal functional connectivity within epileptogenic networks with concomitant contralateral increased connectivity possibly reflecting compensatory mechanisms.     

Rasburicase for tophaceous gout not treatable with allopurinol: an exploratory study

OBJECTIVE: To evaluate the short-term safety and outcome of 2 different experimental applications of rasburicase 0.2 mg/kg (monthly vs daily) in patients with tophaceous gout not treatable by allopurinol. Rasburicase could be useful for patients with gout that is unresponsive to allopurinol or who cannot tolerate the therapy. METHODS: Five patients received 6 monthly infusions of rasburicase (Group 1) and 5 received 5 daily infusions (Group 2). RESULTS: In Group 1, serum uric acid (SUA) level decreased significantly, from 612.6 +/- 162.4 micromol/l at baseline to 341.2 +/- 91.8 micromol/l after 6 infusions (p = 0.001). Changes in tophus area were observed in 2 patients. In Group 2, daily infusions produced a rapid, marked decrease in SUA level during treatment. Yet SUA levels measured at 1 month (511.5 +/- 128.4 micromol/l) and 2 months (572 +/- 96.2 micromol/l) after treatment were not significantly lower than at baseline (573.6 +/- 48.2 micromol/l). No patient from Group 2 showed reduced tophus size. Eight of 10 patients experienced an adverse event, the most common being gout flare despite prophylactic treatment with colchicine. CONCLUSION: Monthly infusions of rasburicase appear to be a possible therapy for severe gout not treatable by other means. Tolerance of rasburicase in gout appears to be diminished by frequent triggering of gout attacks, and hypersensitivity reactions might be an important limitation to longterm therapy.     

High radiosensitivity of germ cells in human male fetus

CONTEXT: Germ cells formed during human fetal life are essential for fertility of the adult, and several studies have described an increasing frequency of male reproductive disorders, which may have a common origin in fetal life and which are hypothesized to be caused by endocrine disruptors. However, factors inducing a genotoxic stress may also be implicated. OBJECTIVES: We investigated the effect of gamma-irradiation on the functions of human fetal testis during the first trimester of gestation by using an organ culture system. Then we focused on the role of the p53 pathway in the observed effects. RESULTS: Germ cells were highly sensitive to irradiation even at doses as low as 0.1 and 0.2 Gy. Indeed, for these doses, one third of germ cells died by apoptosis. Other germ cells were blocked in their cycle, but no repair seemed to occur, and longer culture with the highest dose used showed that they were destined to die. Sertoli cells were less affected, although their proliferation and the level of anti-Müllerian hormone were reduced. Irradiation had no effect on testosterone secretion or on the expression of steroidogenic enzymes by Leydig cells. After irradiation, p53 phosphorylated on serine 15 was detected from 1-24 h in all cell types. This activation of p53 was accompanied by an increase in mRNA levels of proapoptotic factors Bax and Puma, whereas that of antiapoptotic Bcl-2 remained unchanged. P21, which is responsible for cell cycle arrest, was also up-regulated 6, 30, and 72 h after irradiation. Finally, when we added pifithrin-alpha, a specific inhibitor of p53 functions, a significant decrease in irradiation-induced apoptosis in both germ and Sertoli cells was observed, indicating the involvement of the p53 pathway in irradiation-induced apoptosis. CONCLUSIONS: This study demonstrated here for the first time the great sensitivity of human fetal germ cells to genotoxic stress caused by ionizing radiation.     

Expressional and epigenetic alterations of placental serine protease inhibitors: SERPINA3 is a potential marker of preeclampsia

Preeclampsia is the major pregnancy-induced hypertensive disorder. It modifies the expression profile of placental genes, including several serine protease inhibitors (SERPINs). The objective of this study was to perform a systematic expression analysis of these genes in normal and pathological placentas and to pinpoint epigenetic alterations inside their promoter regions. Expression of 18 placental SERPINs was analyzed by quantitative RT-PCR on placentas from pregnancies complicated by preeclampsia, intrauterine growth restriction, or both and was compared with normal controls. SERPINA3, A5, A8, B2, B5, and B7 presented significant differences in expression in >or=1 pathological situation. In parallel, the methylation status of the CpG islands located in their promoter regions was studied on a sample of control and preeclamptic placentas. Ten SERPIN promoters were either totally methylated or totally unmethylated, whereas SERPINA3, A5, and A8 presented complex methylation profiles. For SERPINA3, the analysis was extended to 81 samples and performed by pyrosequencing. For the SERPINA3 CpG island, the average methylation level was significantly diminished in preeclampsia and growth restriction. The hypomethylated CpGs were situated at putative binding sites for developmental and stress response (hypoxia and inflammation) factors. Our results provide one of the first observations of a specific epigenetic alteration in human placental diseases and provide new potential markers for an early diagnosis.