Genome-wide survey of Arabidopsis natural variation in downy mildew resistance using combined association and linkage mapping

The model plant Arabidopsis thaliana exhibits extensive natural variation in resistance to parasites. Immunity is often conferred by resistance (R) genes that permit recognition of specific races of a disease. The number of such R genes and their distribution are poorly understood. In this study, we investigated the basis for resistance to the downy mildew agent Hyaloperonospora arabidopsidis ex parasitica (Hpa) in a global sample of A. thaliana. We implemented a combined genome-wide mapping of resistance using populations of recombinant inbred lines and a collection of wild A. thaliana accessions. We tested the interaction between 96 host genotypes collected worldwide and five strains of Hpa. Then, a fraction of the species-wide resistance was genetically dissected using six recently constructed populations of recombinant inbred lines. We found that resistance is usually governed by single dominant R genes that are concentrated in four genomic regions only. We show that association genetics of resistance to diseases such as downy mildew enables increased mapping resolution from quantitative trait loci interval to candidate gene level. Association patterns in quantitative trait loci intervals indicate that the pool of A. thaliana resistance sources against the tested Hpa isolates may be predominantly confined to six RPP (Resistance to Hpa) loci isolated in previous studies. Our results suggest that combining association and linkage mapping could accelerate resistance gene discovery in plants.     

Brucella Prosthetic Valve Endocarditis: A Systematic Review

ObjectiveBrucella prosthetic valve endocarditis is a rare but a life-threatening complication of brucellosis. It remains a diagnostic challenge. Optimal treatment of Brucella prosthetic valve endocarditis is debated. Available data is limited to case reports or small case series. The purpose of this study was to systematically review all published cases of Brucella prosthetic valve endocarditis in the literature.MethodA systematic review of PubMed database, Google, Google Scholar, and Scopus (From January 1974 to the present) for studies providing epidemiological, clinical and microbiological data as well as data on treatment and outcomes of Brucella prosthetic valve endocarditis was performed.ResultsA total of 51 reported cases were reviewed. Brucella melitensis (45%) and Brucella abortus (11.7%) were the most frequently isolated species. Most common type of prosthesis valve was mechanical prothesis (84.3%) and ten patients had double valve prosthesis (19.6%). Fever and dyspnea were present in 100% and 37.2% of the cases, respectively. The diagnosis was set with echocardiographic finding in 30 cases (93.7%), which revealed vegetation in 27 cases (84.3%). Most used antibiotics were rifampicin, doxycycline and aminoglycoside or cotrimoxazole. No deaths were noted in patients treated by combined medical and surgical treatment, but mortality was noted in 27.7% of the cases treated by antibiotics alone (p = 0.006).ConclusionThis systematic review highlights diagnostic challenges and demonstrates that surgery improved outcome by reducing mortality in patients treated with the combined surgical and medical treatment option. Brucellosis should be considered in the differential diagnosis of prosthetic valve endocarditis in patients residing in or traveling to areas of endemicity.     

Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling

Although patients with advanced refractory solid tumors have poor prognosis, the clinical development of targeted protein kinase inhibitors offers hope for the future treatment of many cancers. In vivo and in vitro studies have shown that the oral multikinase inhibitor, sorafenib, inhibits tumor growth and disrupts tumor microvasculature through antiproliferative, antiangiogenic, and/or proapoptotic effects. Sorafenib has shown antitumor activity in phase II/III trials involving patients with advanced renal cell carcinoma and hepatocellular carcinoma. The multiple molecular targets of sorafenib (the serine/threonine kinase Raf and receptor tyrosine kinases) may explain its broad preclinical and clinical activity. This review highlights the antitumor activity of sorafenib across a variety of tumor types, including renal cell, hepatocellular, breast, and colorectal carcinomas in the preclinical setting. In particular, preclinical evidence that supports the different mechanisms of action of sorafenib is discussed.     

Bone Mineral Density of the Spine and Femur in Healthy Moroccan Women

Bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry (DXA) are widely used to diagnose osteoporosis and assess its severity. Previous studies show the necessity to establish reference data for bone mass measurements for each particular population. Such data are lacking for the Moroccan population. The aim of this study was to determine spine and femur BMD reference values for the Moroccan female population and to compare them with values from western and other Arab countries. A cross-sectional study of 569 Moroccan women, (randomly selected in the area of Rabat, the capital of Morocco, aged between 20 and 79 yr) was carried out to establish reference values of BMD. Measurements were taken at the lumbar spine and proximal femurs using DXA (Lunar Prodigy Vision, GE). The data were compared with published normative data taken by United States (U.S.), European, Kuwaiti, Lebanese, and Saudi women over 6 decades of age. The percentage of osteoporosis in postmenopausal women using our reference curve was compared to that observed when the other curves (US, European and Arab) implemented in the Lunar machine was used. Our results showed that the Moroccan women showed the expected decline in BMD at both sites with age after peaking at 20–29 years of age. Moroccan females have lower BMD at the spine than U.S., Europeans, and Kuwaitis (approximately 10–12% for patients older than 50 yr). The BMD values of the total femur in Moroccan females were close to western (European and American), and Kuwaitis, but higher than Lebanese and Saudis. Using our reference database, 37.9% of postmenopausal women had spine osteoporosis vs. 39.6% and 23.4% using US/European and Arabic Lunar reference values respectively. At the femurs, 6.7% had osteoporosis vs. 2.5% using the Arabic Lunar reference values. In conclusion, our study emphasizes the importance of using population-specific reference values for BMD measurements to avoid over or underdiagnosis of osteoporosis.     

Treatment of painful bony metastases with Samarium 153-EDTMP in prostate carcinoma

THE OBJECTIVE of this work is to evaluate a new therapy, the metabolic radiotherapy to the 153Samarium-EDTMP, of recent introduction in Tunisia, in the painful bony metastasis treatment observed at the patients affected of cancer of the prostate. METHODS: It is about a retrospective survey with a receding of 40 months, achieved through 45 files of patients having benefited all of this new treatment for painful bony metastases in relation with a prostatic adenocarcinoma and collected by three centers of Nuclear Medicine of the capital: the institute Salah Azaiez (state-controlled), the Center CERU (deprives) and the Military hospital (HMPIT). RESULTS: We tried to appreciate essentially four parameters: the therapeutic efficiency, the factors influencing the answer in the treatment, the toxicity of the treatment and the sources of failure. We observed a positive answer in 92,1% of the cases, this answer was complete in 36,5% of the cases. The results gotten after multiple administrations show that the cures could be repeated with results comparable to those of the first cure. The therapeutic efficiency is at least equivalent to those of the other therapeutic means, with nearly non-existent secondary effects. The only toxicity is of hematological order; it is the most often moderate and reversible with a complete recuperation at the end of 8 weeks. Besides, the effect on the pain came with an improvement of the quality of life of the patients treaties. CONCLUSION: Its precocious introduction in the taken in charge of the metastatic patients, would allow them to benefit better from its efficiency, simplicity and weak toxicity and therefore to enjoy a better quality of life.     

Psoas abscess of the adult: study of 38 cases

OBJECTIVE: Our aim is to report the clinical aspects, the etiologies, the treatment and the evolution of the psoas abscess in the adult. METHODS: Our retrospective study concerns 38 cases of psoas abscesses collected in the Department of Infectious Diseases of Sfax (Tunisia), over a period of 16 years (January 1990 - December 2005). RESULTS: The average age is 44 years (extremes: 16-76 years). The sex-ratio is 1.4. Six patients were diabetics and one had a chronic renal injury at the stage of hemodialysis. The clinical manifestations were: a fever (76.4%), an abdomino-pelvic ache (84.2%) and a psoitis (34.2%). All patients had a biologic inflammatory syndrome with a hyperleucocytosis in 28 cases. The abscess was one-sided in 29 cases and bilateral in 9 cases. After microbiological study and/or histological study, pathogens were identified in 31 patients, they were Staphylococcus aureus (10 cases), Staphylococcus lugdunensis (1 case), Streptococci (3 cases), Escherichia coli (2 cases), Bacteroides fragilis (1 case), Actinomyces (2 cases), Brucella (3 cases), Mycobacterium tuberculosis (8 cases) and Candida glabrata (1 case). The psoas abscess was primary in 10 cases and secondary in 28 cases. All the patients received an antibiotherapy or an antifungal therapy adapted to the micro-organism in cause, with a drainage of the abscess in 25 cases (surgical in 9 cases and percutaneous in 16 cases). The evolution was favourable in 36 cases. One patient presented recurrences and one patient died. CONCLUSION: The psoas abscess of the adult is characterized by a polymorphe clinical presentation. Germs in cause are very variable.     

Thyroglobulin: usefulness and limits in monitoring patients with thyroid carcinoma

The aim of this study was to assess the role of thyroglobulin in monitoring patients with differentiated thyroid carcinoma. METHODS: We retrospectively sudied thirty patients who had total thyroidectomy and had been followed beteween 1999 and 2004 in nuclear medicine department. They have had iodine 131 whole body scans, repeated determination of thyroglobulin, thyreostimulin and thyroglobulin antibodies. RESULTS: One hundred twelve samples of thyroglobulin were done. In post surgical period thyroglobulin was ranging from 0.3 to 600 ng/ml. In 38 months follow up 4 patients (11.4%) had shown reccurent disease. Thyroglobulin sensitivity was 75%. One patient had diffuse lung metastases with high thyroglobulin level 600 ng/ml wich decreased after iodine 131 therapy. CONCLUSION: Serum thyroglobulin is the differentiated thyroid carcinoma marker of choice nevertheless one should establish the level of thyroid stimulation and seek for the antithyroglobulin antibodies.     

Characterization of CTX-M and SHV extended-spectrum beta-lactamases and associated resistance genes in Escherichia coli strains of food samples in Tunisia

OBJECTIVES: To assess the occurrence of extended-spectrum beta-lactamases (ESBLs) in Escherichia coli isolates of faecal samples of animals (n = 40) and food samples (n = 38) obtained in Tunisia in 2006, and to characterize the type of ESBLs, their genetic environments and the associated resistance genes. METHODS: Samples were inoculated in supplemented media (2 mg/L cefotaxime) for isolation of broad-spectrum cephalosporin-resistant E. coli isolates (one isolate/sample). ESBLs and their genetic environments as well as integrons and their gene cassette composition were characterized by PCR and sequencing. RESULTS: ESBL-producing E. coli isolates were detected in 10 of the 38 food samples analysed (26%) and in none of the tested animal faecal samples. Genes found were as follows (number of isolates): bla(CTX-M-1) (5), bla(CTX-M-1) + bla(TEM-1b) (1), bla(CTX-M-14) + bla(TEM-1b) (2), bla(CTX-M-8) (1) and bla(SHV-5) (1). All ESBL-positive isolates showed unrelated PFGE patterns. ISEcp1 and IS903 were detected surrounding bla(CTX-M-14), and ISEcp1/IS26 and orf477 surrounding some of the bla(CTX-M-1) genes. Four of the ESBL-positive strains harboured class 1 integrons including different gene cassette combinations. CONCLUSIONS: ESBLs, mainly of the CTX-M class, are detected in E. coli of food origin in Tunisia, being the first time that this mechanism has been detected in food E. coli strains in Africa.     

Accuracy of the TIMI and GRACE scores in predicting coronary disease in patients with non-ST-elevation acute coronary syndrome

Introduction

The GRACE and TIMI scores have been well validated for assessment of prognosis in non-ST-elevation acute coronary syndrome (NSTE-ACS). However, their value in predicting coronary artery disease (CAD) has been little studied. We aimed to assess the relationship between these scores and the extent of coronary disease.

Prevalence and severity of hyponatremia and hypercreatininemia in short-term uncomplicated hypothyroidism

Hypothyroidism is widely accepted as a cause of hyponatremia and hypercreatininemia. However, the prevalence and severity of hyponatremia and hypercreatininemia in hypothyroid patients without comorbid conditions have not been well documented. We retrospectively studied serum sodium and creatinine levels in thyroid-ablated patients with differentiated thyroid cancer off (no.=128) and on (no.=60) thyroid hormone therapy. In the hypothyroid state, mean(+/-SD) TSH, sodium, and creatinine levels were 130.3+/-104.8 mU/l, 139.3+/-2.7 mEq/l, and 89.4+/-20 mmol/l respectively. Twenty-four patients (18.8%) had creatinine levels above the age- and sex-adjusted normal range, whereas only five patients (3.9%) had sodium levels below 135 mEq/l. No patient had a sodium level less than 130 mEq/l. Compared to their euthyroid values, mean sodium and creatinine levels of the hypothyroid patients changed by -1.18 mEq/l (p=0.003) and 17.2 mmol/l (p<0.0001), respectively. There was significant correlation of TSH levels in the hypothyroid state with the changes from the euthyroid state to the hypothyroid state in creatinine levels (r=0.29, p=0.02) but not with the corresponding changes in sodium levels (r=0.06, p=0.6). In thirty-seven patients studied in two hypothyroid episodes, there was a significant correlation between a) TSH levels in hypothyroid state 1 and hypothyroid state 2 (r=0.56, p=0.0003), and b) the change in creatinine levels from the euthyroid state to hypothyroid state 1 and the corresponding change from the euthyroid state to hypothyroid state 2 (r=0.48, p=0.003). There was no significant correlation between the change in sodium levels from the euthyroid state to hypothyroid state 1 and the corresponding change from the euthyroid state to hypothyroid state 2 (r=0.32, p=0.05). We conclude that hyponatremia is very uncommon, whereas mild to moderate elevation in serum creatinine level is not uncommon in patients with short-term uncomplicated hypothyroidism.