Brain metastases after stereotactic radiosurgery using the Leksell gamma knife: can FDG PET help to differentiate radionecrosis from tumour progression?

Stereotactic radiosurgery (SRS) using the Leksell gamma knife promotes acute and chronic local changes in glucose metabolism. We have been able to find very few papers on Medline on the subject of assessment of metastases by 2-[(18)F]fluoro-2-deoxy- D-glucose positron emission tomography (FDG PET) after SRS. The aim of this work was to specify the additional value of FDG PET, in comparison with magnetic resonance imaging (MRI), in differentiating SRS-induced radionecrosis from viable brain metastasis in a clinical setting. Fifty-seven metastases in 25 patients were treated by SRS. An average of 33 weeks later, all the patients underwent FDG PET. At the same time (SD=2 weeks) all the patients underwent MRI. The sensitivity, specificity and accuracy of both FDG PET and MRI examinations were calculated with reference to clinical and radiological follow-up or biopsies. The additional value derived from use of FDG PET after MRI was assessed and progression-free survival rates were compared. The difference in progression-free survival rates between the negative and positive subgroups was significant ( P=0.0005) for MRI and even more so ( P<0.00001) for FDG PET. Sensitivity, specificity and accuracy were 75% (6/8), 93.9% (46/49) and 91.2% (52/57) for FDG PET, and 100% (8/8), 65.3% (32/49) and 70.2% (40/57) for MRI. In the subgroup of patients with positive or non-diagnostic MRI, the probability of presence of a viable tumour was only 32% (8/25). This probability increased to 100% (5/5) when subsequent FDG PET was positive and decreased to 11.1% (2/18) when FDG PET was negative. The frequency of a viable neoplasm was significantly different ( P=0.001) in the FDG PET negative and positive subgroups. MRI and FDG PET both have an important predictive value for persistent viable metastases after treatment by SRS. Neither sensitive but non-specific MRI nor specific but insensitive FDG PET is reliable on its own. While FDG PET significantly improved the diagnostic accuracy in the subgroup of patients with positive and non-diagnostic MRI, it provided no additional value in the MRI-negative subgroup.     

Antimycobacterial and antifungal isosters of salicylamides

A set of 40 derivatives of 3-hydroxypicolinic acid and 2-sulfanylbenzoic acid, isosteric to salicylanilides was synthesized. The compounds were evaluated for in vitro activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium, Candida albicans, Candida tropicalis, Candida krusei, Candida glabrata, Trichosporon beigelii, Aspergillus fumigatus, Absidia corymbifera, Trichophyton mentagrophytes and Microsporum gypseum. Structure-activity relationships of antimycobacterial activity and antifungal activity against T. mentagrophytes and M. gypseum were analyzed by the Free-Wilson method. An increase in antimycobacterial activity was observed only for the sulfanylbenzoic acid derivatives, especially those with the benzyl moiety. The antifungal activity was not significant.     

Nitric oxide donating aspirins: novel drugs for the treatment of saphenous vein graft failure

BACKGROUND: A new class of nitric oxide donating aspirin (NO-ASA) drugs may increase the therapeutic impact of aspirin in saphenous vein coronary artery bypass grafting (CABG) not only through the inhibition of thrombosis but also through a reduction of vasospasm and inhibition of vascular smooth muscle cell (VSMC) proliferation (effects that are inhibited by NO but not ASA). In order to test this proposal the effect of three NO-ASA drugs (NCX4040, NCX4050, and NCX4060) on in vitro relaxation and cyclic guanosine monophosphate (cGMP) formation in the human isolated saphenous vein and the proliferation of human VSMCs was investigated. METHODS: Saphenous vein segments were obtained from 30 patients undergoing CABG (median age, 59 years; range, 49 to 68). The effect of the NO-ASA adducts, ASA alone, and sodium nitroprusside (NO donor) were investigated on (1) relaxation of phenylephrine-stimulated contraction using an organ bath, (2) cyclic guanosine monophosphate (cGMP) formation using an enzyme-linked immunosorbent assay, and (3) the proliferation of VSMCs derived from saphenous vein using bromo-deoxyuridine (BRDU) incorporation. RESULTS: All three NO-ASA adducts (at concentrations that inhibited responses by 50% [IC50s] between 1 micromol/L and 100 micromol/L) and nitroprusside (at IC50s between 0.5 and 10 micromol/L) elicited relaxation of isolated human saphenous vein, promoted cGMP formation, and inhibited VSMC proliferation whereas ASA alone (up to 100 micromol/L) had no effect on any variable. CONCLUSIONS: These data indicate that the NO-ASA adducts by virtue of their capacity to release NO and stimulate guanylyl cyclase may be useful not only in the prevention of thrombosis following CABG but also the reduction of saphenous vein graft spasm and neointima formation.     

TABLE OF AMINO ACID REPLACEMENTS IN PROTEINS POSSIBLE AS A RESULT OF ONE-POINT MUTATIONS

A Table of amino acid replacements based on one-point mutations is presented. For each amino acid replacement the number of mutations of various codons resulting in this mutation is recorded.     

Failure of ergotamine to act as an amplifier of sulfonylurea-stimulated insulin secretion

Summary Normal dogs were injected i.v. with 0.25 mg/kg sodium salt of HB 419 (gliben-clamide) and plasma insulin concentrations were measured over a period of 2 hrs. When the animals were given a single i.v. injection of 0.2 mg/kg dihydroergotamine tartrate (DHE) 30 min prior to the administration of HB 419, the insulinogenic effect of the sulfonylurea was considerably amplified (192 μU/mlvs 34 μU/mI at 45 min). No augmentation of the insulinogenic effect of HB 419 was observed when the same experiments were conducted with 0.05, 0.025 or 0.01 mg/kg ergotamine tartrate. At the dose level of 0.1 mg/kg the insulinogenic effect of HB 419 was suppressed. Since the structural difference between these two ergor alkaloids consists of the presence or absence of the double bond at C₉ and C₁₀ of the lysergic acid moiety, it appears that saturation of this double bond is an essential structural requirement for DHE to function as an amplifier of sulfonylurea-stimulated insulin release. Supported by the Karel Ančerl Fund of the University of Toronto.     

Radioprotective effects of amifostine (WR-2721) or cystamine on radiation damage and its repair in rats whole body exposed to fission neutrons

Sulphur containing radioprotective drugs amifostine (gammaphos, WR-2721) or cystamine (disulfide of meracaptoethylamine) of Czechoslovak production were examined in whole body fission neutrons irradiated rats in the thermal column of reactor VVR-S. Using the split-dose technic the first sublethal neutron dose in the range 1-2 Gy was followed by second lethal exposures in the two time intervals (3 or 6 days) using whole body fission neutrons irradiations (3 days interval) or whole body gamma-irradiations (6 days interval) for LD50/30 evaluation within next 30 days survival observation. In other experiments the mean survival time (MST) in days was estimated in different rats group, when animals were whole body fission neutrons irradiated twice with 3-days interval using the total lethal doses of 4 or 5 Gy. Protected rats received amifostine (160 mg.kg(-1) i.p. and 200 mg.kg(-1) i.m.) or cystamine (40 mg.kg(-1) i.p. and 50 mg.kg(-1) i.m.), control rats obtained saline 20 min before beginning of irradiation in the amount of 0.5 ml.100 g(-1) of the rat's body weight. Non-significant DRF value 1.13 for WR-2721 i.p. was calculated in survival studies in rats twice neutron irradiated with 3 days interval (DRF 1.04 for cystamine). Chemical protectors were administered before each neutron exposure. MST of twice neutron lethal iradiated rats was prolonged not regularly by radioprotectors tested. WR-2721 and cystamine i.m. were not able to increase 6 days reparation processes after sublethal 2 Gy fission neutrons whole body irradiated rats.     

Magnetic marker localisation in breast cancer surgery

Since mammographic screening programmes were initiated, the spectrum of breast cancer has changed in terms of impalpable tumours, thus causing the development of new localisation methods, including magnetic markers. We offer herein an up-to-date review focused on two magnetic markers (Magseed, MaMaLoc) currently used in breast cancer surgery for the localisation of breast tumours or pathological axillary nodes. Magnetic marker localisation presents a safe and reliable method for breast tumour marking. Four currently available prospective studies demonstrate that the Magseed system has a negative margin rate and a successful localisation rate, both of which are comparable to standard marking systems used in breast cancer surgery. The main benefits of magnetic markers are that they require no radiation safety measures, and they offer the possibility of longer deployment times, thus simplifying surgery scheduling. The most important drawbacks are cost of the system, depth limitation and need for frequent probe recalibration.     

Beta-glucans in higher fungi and their health effects

Together with chitin, the β-glucans are components of mycetes' cell walls. A high level of biological efficiency has been found in β-glucans, especially β-1,3-D-glucans and β-1,6-D-glucans isolated from some basidiomycetes. (Biological efficiency refers to the relative ability of β-glucans to promote a desired response, for example to induce leukocyte activation and to produce inflammatory mediators.) These polysaccharides increase the number of Th1 lymphocytes, which help protect organisms against allergic reactions. A number of β-glucans, for example pleuran from Oyster ( Pleurotus spp.) mushrooms or lentinan from Shiitake ( Lentinus edodes ) mushrooms, have shown marked anticarcinogenic activity. In addition to having an immunity-stimulating effect, β-glucans may participate in physiological processes related to the metabolism of fats in the human body. Their application results in a decrease in the total cholesterol content in blood and may also contribute to reductions in body weight.     

Pneumococcal urinary antigen positivity in healthy colonized children: is it age dependent?

Background

Pneumococcal urinary antigen test is a valuable tool for diagnosing pneumococcal pneumonia and meningitis in adults. Its use in children is generally not accepted because of nonspecificity at this age. It is frequently positive in asymptomatic nasopharyngeal carriers. The aim of our study was to assess the age limit from which the test is no longer positive in asymptomatic healthy carriers.

Methods

A total of 197 children aged 36–83 months attending 9 day care centers in Prague were enrolled during February and March 2010. Nasopharyngeal swab specimens were collected from each participant and selectively cultivated. The presence of pneumococcal antigen in urine was detected by BinaxNOW® S. pneumoniae kit.

Results

Streptococcus pneumoniae was cultivated in 53.3 % of healthy children with the highest colonization rate (59.3 %) in children aged 48–59 months. The most frequently colonizing serotypes were: 19F, 23F, 3, 19A, 6B and 4. The presence of pneumococcal antigen in urine decreased with age from 39.0 % in 36–47 months to 17.9 % in 72–83 months old (p = 0.031). The antigen positivity was serotype-dependent and more frequent in nonvaccinated children.

Conclusion

We demonstrated age-dependent linear decrease of pneumococcal antigen excretion into urine in healthy children. The positivity rate of the test in children aged 72–83 months was similar to that referred in healthy adults, irrespective of colonization. To confirm this age limit for use of this test in diagnostics of pneumococcal diseases, further study in school-age children is justified.