289 research outputs found
Recommended from our members
Situation confuse en république démocratique du congo (ex-zaire): jeux et enjeux autour d une tragédie (note d analyse du 15 aout 1998).
Document collected by the University of Texas Libraries from the web-site of the Reseau Documentaire International Sur La Region Des Grands Lacs Africains (International Documentation Network on the Great African Lakes Region). The Reseau distributes "gray literature", non-published or limited distribution government or NGO documents regarding the Great Lakes area of central Africa including Rwanda, Burundi, and the Democratic Republic of Congo.UT Librarie
Male osteoporosis: diagnosis and fracture risk evaluation
Male osteoporosis is challenging to diagnose and to treat. Underestimation of the risk of male osteoporosis, the combined presence of several interwoven causative factors in many patients, and uncertainty regarding the absorptiometry cutoffs associated with fractures are major obstacles to the diagnosis of male osteoporosis and to the identification of men at risk for fractures. The lifetime risk of osteoporotic fracture is estimated at 15% among men older than 50 years. One-third of proximal femoral fractures occur in men, and the associated mortality rate is 2- to 3-fold that in women. In men, nearly half the cases of osteoporosis are related to disease, medications, or risk factors. Although the criteria for diagnosing male osteoporosis are not agreed on, the definitions developed by the World Health Organization can be used provided the reference population is composed of young males. An absorptiometry T-score < or = -2.5 is useful for diagnosing osteoporosis but fails to adequately predict the fracture risk. The identification of men at high risk for fractures requires a combined evaluation of bone mineral density data, clinical risk factors, and risk factors for falls
Compliance with recommendations of clinical practice in the management of venous thromboembolism in cancer: the CARMEN study
Cancer is associated with venous thromboembolism in 20% of patients. In such patients, thrombosis is difficult to treat, associated with bleeding, recurrence, and death. Specific treatments for venous thromboembolism in cancer are recommended. Guidelines have been implemented in many countries and international guidelines have been recently developed. We evaluated the adhesion to national French guidelines via a survey of cancer patients treated for venous thromboembolism. METHODS: A national cross-sectional observational study evaluated the adhesion to guidelines in hospitalized patients. Good clinical practice was defined as initial 10-day treatment with injectable molecules followed by long-term treatment with low molecular weight heparin for at least 3 months. Demographic data, cancer type, stage, treatment, risk factors and type of thrombosis, were recorded. RESULTS: Five patients were included in 47 centers. Overall adhesion to guidelines was present in 59% (55-63%) of patients (295/500). During initial treatment, adhesion was high (487/496; 98%) but dropped (296/486; 62%) during the long-term maintenance. In patients with renal insufficiency, only a fourth of them received the adequate treatment. A majority of patients had metastatic disease (64%). Cancer sites were gastro-intestinal (25%), gynecologic (23%), pulmonary (21%), hematological (14%), urologic (10%), or other (8%). Lung and hematological malignancies were significantly associated with the highest and lowest rates of adhesion. CONCLUSION: Adhesion to national guidelines for treatment of venous thromboembolism in cancer is not optimal. Good compliance is observed during initial treatment, but drops after 10 days, underlying the need for further education to achieve a better implementation on a national level
The variability properties of X-ray steep and X-ray flat quasars
We have studied the variability of 6 low redshift, radio quiet `PG' quasars
on three timescales (days, weeks, and months) using the ROSAT HRI. The quasars
were chosen to lie at the two extreme ends of the ROSAT PSPC spectral index
distribution and hence of the H FWHM distribution. The observation
strategy has been carefully designed to provide even sampling on these three
basic timescales and to provide a uniform sampling among the quasars We have
found clear evidence that the X-ray steep, narrow H_beta, quasars
systematically show larger amplitude variations than the X-ray flat broad
H_beta quasars on timescales from 2 days to 20 days. On longer timescales we do
not find significant differences between steep and flat quasars, although the
statistics are poorer. We suggest that the above correlation between
variability properties and spectral steepness can be explained in a scenario in
which the X-ray steep, narrow line objects are in a higher L/L_Edd state with
respect to the X-ray flat, broad line objects. We evaluated the power spectrum
of PG1440+356 (the brigthest quasar in our sample) between 2E-7 and 1E-3 Hz,
where it goes into the noise. The power spectrum is roughly consistent with a
1/f law between 1E-3 and 2E-6 Hz. Below this frequency it flattens
significantly.Comment: ApJ in pres
Childhood chronic prurigo: Interest in patch tests and delayed-reading skin prick tests to environmental allergens
p.Ala541Thr variant of MEN1 gene: A non deleterious polymorphism or a pathogenic mutation?
Context
Multiple Endocrine Neoplasia Type 1 (MEN1) is an autosomal dominant inherited syndrome, related to mutations in the MEN1 gene. Controversial data suggest that the nonsynonymous p.Ala541Thr variant, usually considered as a non-pathogenic polymorphism, may be associated with an increased risk of MEN1-related lesions in carriers.
Objective
The aim of this study was to evaluate the pathogenic influence of the p.Ala541Thr variant on clinical and functional outcomes.
Patients and methods
We analysed a series of 55 index patients carrying the p.Ala541Thr variant. Their clinical profile was compared to that of 117 MEN1 patients. The biological impact of the p.Ala541Thr variant on cell growth was additionally investigated on menin-deficient Leydig cell tumour (LCT)10 cells generated from Men1+/Men1− heterozygous knock-out mice, and compared with wild type (WT).
Results
The mean age at first appearance of endocrine lesions was similar in both p.Ala541Thr carriers and MEN1 patients, but no p.Ala541Thr patient had more than one cardinal MEN1 lesion at initial diagnosis. A second MEN1 lesion was diagnosed in 13% of MEN1 patients and in 7% of p.Ala541Thr carriers in the year following preliminary diagnosis. Functional studies on LCT10 cells showed that overexpression of the p.Ala541Thr variant did not inhibit cell growth, which is in direct contrast to results obtained from investigation of WT menin protein.
Conclusion
Taken together, these data raise the question of a potential pathogenicity of the p.Ala541Thr missense variant of menin that commonly occurs within the general population. Additional studies are required to investigate whether it may be involved in a low-penetrance MEN1 phenotype
Spectrum of HNF1A Somatic Mutations in Hepatocellular Adenoma Differs From That in Patients With MODY3 and Suggests Genotoxic Damage
OBJECTIVE Maturity onset diabetes of the young type 3 (MODY3) is a consequence of heterozygous germline mutation in HNF1A. A subtype of hepatocellular adenoma (HCA) is also caused by biallelic somatic HNF1A mutations (H-HCA), and rare HCA may be related to MODY3. To better understand a relationship between the development of MODY3 and HCA, we compared both germline and somatic spectra of HNF1A mutations.
RESEARCH DESIGN AND METHODS We compared 151 somatic HNF1A mutations in HCA with 364 germline mutations described in MODY3. We searched for genotoxic and oxidative stress features in HCA and surrounding liver tissue.
RESULTS A spectrum of HNF1A somatic mutations significantly differed from the germline changes in MODY3. In HCA, we identified a specific hot spot at codon 206, nonsense and frameshift mutations mainly in the NH2-terminal part, and almost all amino acid substitutions were restricted to the POU-H domain. The high frequency of G-to-T tranversions, predominantly found on the nontranscribed DNA strand, suggested a genotoxic mechanism. However, no features of oxidative stress were observed in the nontumor liver tissue. Finally, in a few MODY3 patients with HNF1A germline mutation leading to amino acid substitutions outside the POU-H domain, we identified a different subtype of HCA either with a gp130 and/or CTNNB1 activating mutation.
CONCLUSIONS Germline HNF1A mutations could be associated with different molecular subtypes of HCA. H-HCA showed mutations profoundly inactivating hepatocyte nuclear factor-1α function; they are associated with a genotoxic signature suggesting a specific toxicant exposure that could be associated with genetic predisposition
Performance of the ROX index to predict intubation in immunocompromised patients receiving high-flow nasal cannula for acute respiratory failure
Background Delayed intubation is associated with high mortality. There is a lack of objective criteria to decide the time of intubation. We assessed a recently described combined oxygenation index (ROX index) to predict intubation in immunocompromised patients. The study is a secondary analysis of randomized trials in immunocompromised patients, including all patients who received high-flow nasal cannula (HFNC). The first objective was to evaluate the accuracy of the ROX index to predict intubation for patients with acute respiratory failure. Results In the study, 302 patients received HFNC. Acute respiratory failure was mostly related to pneumonia (n = 150, 49.7%). Within 2 (1-3) days, 115 (38.1%) patients were intubated. The ICU mortality rate was 27.4% (n = 83). At 6 h, the ROX index was lower for patients who needed intubation compared with those who did not [4.79 (3.69-7.01) vs. 6.10 (4.48-8.68), p < 0.001]. The accuracy of the ROX index to predict intubation was poor [AUC = 0.623 (0.557-0.689)], with low performance using the threshold previously found (4.88). In multivariate analysis, a higher ROX index was still independently associated with a lower intubation rate (OR = 0.89 [0.82-0.96], p = 0.04). Conclusion A ROX index greater than 4.88 appears to have a poor ability to predict intubation in immunocompromised patients with acute respiratory failure, although it remains highly associated with the risk of intubation and may be useful to stratify such risk in future studies
Evaluation of DNA methylation episignatures for diagnosis and phenotype correlations in 42 Mendelian neurodevelopmental disorders
Efficacy of the combination of long-acting release octreotide and tamoxifen in patients with advanced hepatocellular carcinoma: a randomised multicentre phase III study
To assess the efficacy of the combination of long-acting release (LAR) octreotide and tamoxifen (TMX) for the treatment of advanced hepatocellular carcinoma (HCC). A total of 109 patients with advanced HCC were randomised to receive octreotide LAR combined with TMX (n=56) (experimental treatment group) or TMX alone (n=53; control group). The clinical, biological and tumoural parameters were recorded every 3 months until death. Primary end point was patient survival; secondary end points were the impact of therapy on tumour response, quality of life and variceal bleeding episodes. Univariate and multivariate analyses were performed for assessment of specific prognostic factors. The median survival was 3 months (95% CI 1.4–4.6) for the experimental treatment group and 6 months (CI 95% 2–10) for the control group (P=0.609). There was no difference in terms of α-foetoprotein (α-FP) decrease, tumour regression, improvement of quality of life and prevention of variceal bleeding between the two groups. Variables associated with a better survival in the multivariate analysis were: presence of cirrhosis, α-FP level <400 ng ml−1 and Okuda stage I. The combination of octreotide LAR and TMX does not influence survival, tumour progression or quality of life in patients with advanced HCC
- …