Metasynchronous bilateral Achilles tendon rupture

Although Achilles tendon ruptures are a common occurrence, bilateral ruptures of the Achilles tendon are not. We present the case of a 33-year-old female who sustained metasynchronous (i.e., very close in time) bilateral ruptures of her Achilles tendons with no obvious predisposing factors. She was treated using a percutaneous technique and six months following surgery has returned to her normal activities.     

Breast cancer metastatic to the choroid in a male patient: case report

Choroidal metastases have been observed in about 8% of patients with metastatic breast cancer, even if their true incidence is likely to be higher, as they are not routinely investigated in the absence of symptoms. Radiotherapy is the treatment of choice for symptom palliation. The prognosis is traditionally poor, with a reported average survival of one year. Here we describe the third case reported in the literature of a metastatic tumor to the choroid from a male breast carcinoma.     

Virtual simulation: fifteen years later

In the last two decades there was a radical change in radiotherapy setup. The growing availability of CT equipment and console for computer-aided treatment planning setup enabled the use of advanced technologies as conformal 3D radiation therapy in most centers. In particular in 1987 virtual simulation was proposed for setup. During its use a number of application modalities appeared. Virtual simulation in some centers is applied alone while in others it is associated with conventional simulation. However, from numerous reports published in last years it seems that virtual simulation significantly improves treatment quality independently of radical or palliative intent and of the size of treated volumes (high doses to small volumes or wide shaped fields). Some studies stressed that virtual simulation could significantly shorten treatment planning times with consequent cost reduction. The use of virtual simulation evidenced associated problems and in particular setup limitations due to the CT gantry size, the need to up-date the conventional modalities of setup verification according to the new technologies and more generally to up-date quality assurance procedures in an advanced technological setting. Finally there was the self-evident need of a better knowledge of the anatomy on axial sections, of tumor spread routes in particular.     

Downregulation of bcl-2 expression in lymphoma cells by bcl-2 ARE-targeted modified,synthetic ribozyme

Synthetic ribozymes are catalytic RNA molecules designed to inhibit gene expression by cleaving specific mRNA sequences. We investigated the potential of synthetic ribozymes to inhibit bcl-2 expression in apoptosis defective bcl-2 overexpressing tumors. A chemically stabilized hammerhead ribozyme has been targeted to the A+U-rich regulative element of bcl-2 mRNA that is involved in bcl-2 gene switch-off during apoptosis. The design of the ribozyme was based on the results of probing accessibility of the RNA target in cellular extracts with antisense DNA. The ribozyme was lipotransfected to a bcl-2 overexpressing human lymphoma cell line (Raji). The cellular uptake of this ribozyme resulted in a marked reduction of both bcl-2 mRNA and BCL-2 protein levels and dramatically increased cellular death by apoptosis. Our results suggest a potential therapeutic application of such ribozyme for the treatment of bcl-2 overexpressing tumors.     

A Nodal- and ALK4-independent signaling pathway activated by Cripto-1 through Glypican-1 and c-Src

Human Cripto-1 (CR-1) is a member of the epidermal growth factor-Cripto FRL1 Cryptic family that has been shown to function as a coreceptor with the type I Activin serine-threonine kinase receptor ALK4 for the transforming growth factor beta-related peptide Nodal. However, CR-1 can also activate the mitogen-activated protein kinase and Akt pathways independently of Nodal and ALK4 by an unknown mechanism. Here, we demonstrate that CR-1 specifically binds to Glypican-1, a membrane-associated heparan sulfate proteoglycan, and activates the tyrosine kinase c-Src, triggering the mitogen-activated protein kinase and Akt signaling pathways. Finally, an active Src kinase is necessary for CR-1 to induce in vitro transformation and migration in mouse mammary epithelial cells.     

Bioactive asterosaponins from the starfish Luidia quinaria and Psilaster cassiope. Isolation and structure characterization by two-dimensional NMR spectroscopy

An investigation of the polar extracts from two starfish, Luidia quinaria and Psilaster cassiope, led to the isolation of five sulfated "asterosaponins". Two of them, named luidiaquinoside (1) and psilasteroside (2), are new compounds. Luidiaquinoside (1) contains a novel pentasaccharide chain composed of d-glucose, d-quinovose, and d-fucose, with the d-glucose unit being the branching point. Psilasteroside (2) contains a hexasaccharide chain in which an arabinose residue is detectable in the furanose form. Both of these compounds possess a Delta(9(11)),3beta,6alpha-dihydroxysteroidal nucleus with a 20-hydroxy, 23-oxo functionality. The structures of the new asterosaponins were elucidated by a combination of NMR techniques including (1)H-(1)H (COSY, TOCSY, and ROESY) and (1)H-(13)C (HMQC and HMBC) spectroscopy, ESIMS and HRFABMS spectrometry, and GC analyses. The new asterosaponins show marginal in vitro cytotoxicity against RBL-2H3 (rat basophilic leukemia) cell lines.     

Effect of family history of type 2 diabetes on white blood cell count in adult women

OBJECTIVE: To evaluate the effect of a first-degree family history of type 2 diabetes on white blood cell (WBC) count, a risk factor for atherosclerotic vascular disease, in glucose-tolerant adult women. RESEARCH METHODS AND PROCEDURES: WBC count was measured in 174 normal weight, overweight, and obese female offspring of type 2 diabetic patients (FH(+)) and 174 age- and BMI-matched female controls with no family history of type 2 diabetes (FH(-)). Other measurements included fat mass (FM), measured by body impedance analysis; central fat accumulation, evaluated by waist circumference; insulin resistance, estimated by homeostatic model assessment for insulin resistance (HOMA(IR)); systolic and diastolic blood pressure; and fasting concentrations of glucose, insulin, and lipids. RESULTS: WBC count, waist circumference, systolic blood pressure, and fasting levels of glucose, insulin, and triglycerides were significantly higher in FH(+) than in FH(-) subjects. In FH(+) individuals, WBC count was positively associated with BMI, FM, waist circumference, HOMA(IR), and triglyceride and insulin concentrations, and negatively correlated with age and high-density lipoprotein-cholesterol. In FH(-) subjects, WBC count was directly associated with BMI, FM, waist circumference, and triglyceride and insulin concentrations, and inversely correlated with age and high-density lipoprotein-cholesterol. After multivariate analyses, WBC count maintained a significant association with age, systolic blood pressure, and HOMA(IR) in FH(+) subjects and with age, BMI, FM, and triglycerides in FH(-) individuals. DISCUSSION: This study indicates that WBC count is increased in adult women with genetic predisposition to type 2 diabetes, and its main correlates are insulin resistance in FH(+) and adiposity in FH(-) individuals.     

The employment,attitudes and aspirations of non-training grade doctors

Acute care in the NHS is increasingly delivered by junior doctors who receive little educational supervision. There is a continuing dramatic increase in the numbers of trust doctors. Staff grades are also increasing in number and face many frustrations.     

Comparative bactericidal activity of fluoroquinolones against clinical isolates resistant to fluoroquinolones

The bactericidal activity of levofloxacin, ciprofloxacin, moxifloxacin and norfloxacin against clinical isolates conventionally classified as resistant to fluoroquinolones were compared at their maximum concentrations in serum, urine (except moxifloxacin) and bronchial mucosa (except norfloxacin). Time killing curves against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Streptococcus pneumoniae were performed. Serum concentrations of the tested drugs were not able to produce a bactericidal effect on fluoroquinolone-resistant strains. In the urine series, levofloxacin was always bactericidal (decrease > or = 3 logs CFU/ml), while norfloxacin and ciprofloxacin were bactericidal on E. coli (both), P. mirabilis (norfloxacin) and P. aeruginosa (ciprofloxacin). In the bronchial mucosa series, S. pneumoniae was rapidly killed by levofloxacin and moxifloxacin, and K. pneumoniae by levofloxacin after 12 hours. In conclusion, the maximum levofloxacin concentrations achievable at certain body sites allowed killing even of strains defined as resistant by conventional breakpoints.