Imatinib mesylate in chordoma

BACKGROUND: To the authors' knowledge, no effective medical therapy currently is available for advanced chordoma. Imatinib mesylate is a tyrosine kinase inhibitor targeting platelet-derived growth factor receptor-beta (PDGFRB), BCR-ABL, and KIT. METHODS: Six patients with advanced chordoma were treated with imatinib mesylate at a dose of 800 mg daily. In all patients, the tumor was found to be positive for PDGFRB, and in four patients PDGFRB was shown to be phosphorylated/expressed. RESULTS: After a treatment period of > or = 1 year, overt tumor liquefaction was evident on computed tomography (CT) scan in the first patient. In previous months, a decrease in contrast enhancement on magnetic resonance imaging (MRI) and a decrease in glucose uptake on positron emission tomography (PET) were detected. Similar signs on MRI and PET were observed in subsequent patients, who had a shorter treatment period. One of these patients initially was removed from therapy and then was readmitted to therapy because of difficulties with regard to tumor response assessment; 1 month after the reinitiation of therapy, an overt decrease in tumor density was visible on CT scan in this patient. In four of five symptomatic patients, a subjective improvement was observed early in the course of treatment. The first patient died after 17 months, with a sizeable, mostly liquefied mass. Another patient died early, apparently of unrelated causes. The remaining patients were on therapy at the time of last follow-up. CONCLUSIONS: Imatinib mesylate has been found to have antitumor activity in patients with chordoma. This activity might be mediated by inactivation of PDGFRB. Tumor response manifests through patterns that are similar to those observed in patients with gastrointestinal stromal tumors who respond to molecular-targeted therapy, but evolves more slowly. The benefit to the patient entailed by this pattern of tumor response in chordoma needs to be elucidated, but may be limited in the presence of significant local disease.     

Malignant hypertension and cerebral haemorrhage in Seckel syndrome

Seckel syndrome is an autosomal recessive condition with severe short stature and facial and neurological anomalies. Intracranial haemorrhage, due to rupture of a cerebral aneurysm, is a very rare complication of this syndrome. Malignant hypertension may play an important role in the aetiology of the aneurysm and early detection is essential in order to prevent organ damage. Conclusion:we report a new case of Seckel syndrome associated with malignant hypertension and cerebral haemorrhage.Abbreviations BA basilar artery - MCA middle cerebral artery - PICA posterior internal cerebral artery - PICU paediatric intensive care unit - SS Seckel syndrome     

Intratumoral color Doppler analysis in endometrial carcinoma: is it clinically useful?

OBJECTIVE: The aim was to study the effectiveness of subjective color Doppler evaluation and spectral Doppler parameters in preoperative characterization of endometrial carcinomas. METHODS: Seventy-six patients with endometrial carcinoma were preoperatively analyzed by color Doppler ultrasound in order to subjectively evaluate the amount of intratumoral blood flow (color score) and to analyze the lowest resistance index (RI), the highest peak systolic velocity (PV), and the highest time averaged maximum velocity (TAMVX). These parameters were analyzed according to clinico-pathological characteristics. RESULTS: In 13 patients no intratumoral arterial vessels were detected by color Doppler examination. No lymph node metastases were found in this group of patients. Positive nodes were found in 24% of patients with detectable arterial vessels, although the difference did not reach the statistical significance. No differences were found in spectral Doppler parameters (RI, PV, TAMVX) according to tumor characteristics or nodal involvement. A higher percentage of cases with a color score of 3 was found in stage >I than in stage I patients (69 vs 42%, P < 0.05), and in patients with myometrial invasion greater than 50% than in those with less than 50% invasion (72 vs 38%; P = 0.05). CONCLUSIONS: Nodal metastases were found in 24% of patients with detectable vessels at color Doppler examination. Subjective analysis of vessel density correlated >50%, myometrial invasion, but spectral Doppler analysis was not predictive of surgical stage, tumor grade, myometrial invasion, or lymph node metastases. These results do not support the use of preoperative intratumoral blood flow analysis as a clinical test in evaluating tumor characteristics or in predicting lymph node metastases.     

Metallic biomaterials TiN-coated: corrosion analysis and biocompatibility

Corrosion processes due to contact with the physiological environment should be avoided or minimized in orthopedic implants. Four metallic substrates frequently used as biomaterials: pure Ti, Ti-6Al-4V alloy, ASTM F138 stainless steel, and Co-Cr-Mo alloy, were coated with TiN using the physical vapor deposition (PVD) technique. These coatings have been screened by polarization curves in physiological solutions. TiN prepared by PVD is efficient as coating for stainless steel. On titanium and alloy there are no benefits concerning the corrosion resistance compared to the bare Ti-materials. TiN coatings have been screened according to ISO 10993 standard tests for biocompatibility and exhibited no cytotoxicity, dermal irritation, or acute systemic toxicity response.     

Corticotropin-releasing factor (CRF) and related peptides confer neuroprotection via type 1 CRF receptors

Corticotropin-releasing factor (CRF) receptors are members of the superfamily of G-protein coupled receptors that utilise adenylate cyclase and subsequent production of cAMP for signal transduction in many tissues. Activation of cAMP-dependent pathways, through elevation of intracellular cAMP levels is known to promote survival of a large variety of central and peripheral neuronal populations. Utilising cultured primary rat central nervous system neurons, we show that stimulation of endogenous cAMP signalling pathways by forskolin confers neuroprotection, whilst inhibition of this pathway triggers neuronal death. CRF and the related CRF family peptides urotensin I, urocortin, and sauvagine, which also induced cAMP production, prevented the apoptotic death of cerebellar granule neurons triggered by inhibition of phosphatidylinositol kinase-3 pathway activity with LY294002. These effects were negated by the highly selective CRF-R1 antagonist CP154,526. CRF even conferred neuroprotection when its application was delayed by up to 8 h following LY294002 addition. The CRF peptides also protected cortical and hippocampal neurons against death induced by beta-amyloid peptide (1-42), in a CRF-R1 dependent manner. In separate experiments, LY294002 reduced neuronal protein kinase B activity while increasing glycogen synthase kinase-3, whilst CRF (and related peptides) promoted phosphorylation of glycogen synthase kinase-3 without protein kinase B activation. Taken together, these results suggest that the neuroprotective activity of CRF may involve cAMP-dependent phosphorylation of glycogen synthase kinase-3.     

Gastric surgery as a long-term risk factor for malignant lesions of the larynx

BACKGROUND: Duodenogastroesophageal reflux is common after total or partial gastrectomy. No data are available on the effect of duodenal reflux on the larynx. HYPOTHESIS: Premalignant or malignant changes occur more frequently among subjects with gastric surgery. DESIGN: Historical cohort study. SETTING: Outpatient setting for upper endoscopy. PATIENTS: Ninety-three subjects who had undergone gastric resection at least 5 years previously, and 93 matched dyspeptic individuals who did not undergo gastric surgery. INTERVENTION: Clinical histories of all patients were obtained and recorded. All subjects underwent an otolaryngologic evaluation. RESULTS: Of 93 patients with gastric resection, 7 patients had current or previous laryngeal malignancies or current precancerous mucosal changes. In the control group, 1 subject had a leukoplakia on the vocal cord. The adjusted odds ratio (having included sex, age, and alcohol [yes or no] and smoking [yes or no] history in the regression model) was 9.88 (95% confidence interval, 1.01-97.31; likelihood ratio chi2 = 28.77; P<.001). Furthermore, there was a significant increased prevalence of benign laryngeal lesions in patients with gastric resection vs the control group. CONCLUSIONS: The risk of developing laryngeal malignancies is higher for patients with gastric resection. A periodic otolaryngologic evaluation in subjects with gastric surgery may contribute to early diagnosis of laryngeal disorders.     

Diplopyrone,a new phytotoxic tetrahydropyranpyran-2-one produced by Diplodia mutila,a fungus pathogen of cork oak

A new phytotoxic monosubstituted tetrahydropyranpyran-2-one, named diplopyrone (1), was isolated from the liquid culture filtrates of Diplodia mutila, a plant pathogenic fungus causing a form of canker disease of cork oak (Quercus suber). Diplopyrone was characterized, using spectroscopic and chemical methods, as 6-[(1S)-1-hydroxyethyl]-2,4a,6,8a-tetrahydropyran[3,2-b]pyran-2-one. The absolute stereochemistry of the chiral secondary hydroxylated carbon (C-9), determined by application of Mosher's method, proved to be S. Diplopyrone assayed at a 0.01-0.1 mg/mL concentration range caused necrosis and wilting on cork oak cuttings. On a nonhost plant, tomato, diplopyrone caused brown discoloration or stewing on the stem.