Hemispheric infiltrative grade II gliomas in adults: association of residual tumour volume and extent of tumour resection with malignant transformation.

OBJECTIVES: Evaluation of the impact of surgical treatment on malignant transformation (MT) of adult supratentorial infiltrative grade II gliomas (G2G) in a series of chemotherapy and radiotherapy-naïve patients. BACKGROUND: Despite G2G are slow-growing tumours, they typically undergo MT with a subsequent fatal disease course. An extensive resection alone likely changes their biological behaviour and defers MT; however, this impact is not unequivocally confirmed. METHODS: Thirty-eight chemotherapy and radiotherapy-naïve adult patients operated from 2005 till 2014 for a G2G were investigated. Based on postoperative magnetic resonance imaging (MRI) and/or positron emission tomography follow-up (FU) scans, the patients were classified as "transformers" (15 patients in whom MT occurred during the FU-period) and "non-transformers" (23 patients). RESULTS: The follow-up period of "non-transformers" was longer (p <0.0001). After adjustment for known risk factors - age, male sex, astrocytoma histology, preoperative tumour volume, preoperative contrast enhancement and positive isocitrate dehydrogenase 1 gene mutation status - a larger log postoperative tumour volume (p=0.031) and a smaller extent of resection (p=0.0086) were associated with a shorter MT-free survival. CONCLUSION: In our series, less extensive resections were associated with a shorter time to MT. Our data support an adoption of techniques enabling extensive G2G resections, such as intraoperative imaging and awake resections, into everyday routine (Tab. 1, Fig. 2, Ref. 40).

The value of routine screening for peripheral arterial disease in stable outpatients with a history of coronary artery or cerebrovascular disease.

BACKGROUND: Frequently unrecognised, PAD is associated with reduced quality of life and an increased mortality rate because of a greater propensity for fatal ischaemic events. PAD commonly coexists with coronary and cerebrovascular disease and is associated with poorer outcomes in such patients. The Edinburgh Claudication Questionnaire (ECQ) and the ankle-brachial index (ABI) are screening methods to identify the presence of PAD. This study used these methods to estimate the rate of previously undiagnosed PAD and to validate the ECQ against ABI in a Canadian outpatient population with manifest cerebrovascular or coronary disease. METHODS: At a regular office visit, patients completed the ECQ and were categorised as ECQ(+) or ECQ(-). All ECQ(+) and a randomly selected 25% of ECQ(-) patients were referred for ABI measurement. An ABI < 0.9 was considered positive. The prevalence of PAD in the patient population and the sensitivity and specificity of the ECQ score against the ABI were assessed. RESULTS: Of 2235 patients enrolled, 815 were selected for an ABI [ECQ(-), n = 478; ECQ(+), n = 337]. Extrapolated PAD prevalence in the total population was 12.3% (highest arterial pressure [HAP] method) and 20.8% (lowest arterial pressure [LAP] method), with a significantly higher prevalence found in diabetic patients than non-diabetic patients (p < 0.0001). Because ECQ is only a measure of symptomatic disease, it had poor sensitivity (35.3% and 25.8%), but high specificity (88.2% and 88.3%) using the HAP and LAP methods of ABI measurement, respectively. CONCLUSIONS: Undiagnosed PAD is common in stable outpatients with a prior history of manifest cardiovascular disease, particularly in those with diabetes. The ECQ does not possess the diagnostic value of the ABI in detecting PAD in this high-risk population, but may be useful to raise suspicion of PAD to be confirmed by ABI assessment.

Repression of intestinal drug metabolizing enzymes by the SV40 large T antigen.

Toxic compounds such as carcinogens are removed from the body by the action of a series of detoxifying enzymes and transporters expressed in the liver and the small intestine. We have found that intestinal epithelial cells expressing the SV40 large T antigen (TAg) contain significantly lower levels of mRNAs, encoding several drug metabolizing/detoxifying enzymes and transporters compared to their non-transgenic littermates. In addition, TAg blocks the induction of these mRNAs by xenobiotics. The repression depends on an intact LXCXE motif in TAg, suggesting that inactivation of the retinoblastoma (Rb) family of tumor suppressors plays a role in the process. These results imply that a functional Rb pathway in the intestine is necessary for the expression of the detoxification system used to clear carcinogens, and suggest that loss of this tumor suppressor might alter susceptibility to chemical injury. In addition, the effect of TAg on the detoxification pathway appears to be tissue-specific, as its ectopic expression in the liver failed to suppress the P450 enzymes. The TAg-mediated suppression of drug metabolizing/detoxifying enzymes may have broad implications in the metabolism and mechanism of action of both carcinogens and prescription drugs.

Analytical investigation of plasma-treated carbon fibres.

As-grown and heat-treated vapour grown carbon fibres (VGCF) in the as-prepared state, washed in HCl/H(2)O, and treated in O(2) plasma for different periods have been investigated by means of XPS and scanning electron microscopy (SEM). The surface energy of the carbon fibres before and after plasma treatment was determined from the wetting contact angle. Washing introduced hydroxyl, carbonyl and carboxyl groups onto the fibre surfaces and oxygen plasma treatment increases the total atomic concentration of oxygen up to 17%. This is in good agreement with the value of the polar component of the surface energy. Plasma treatment also enhanced the fibre surface porosity (by etching).

Behavioral rhythmicity, age, division of labor and period expression in the honey bee brain.

Young adult honey bees work inside the beehive "nursing" brood around the clock with no circadian rhythms; older bees forage for nectar and pollen outside with strong circadian rhythms. Previous research has shown that the development of an endogenous rhythm of activity is also seen in the laboratory in a constant environment. Newly emerging bees maintained in isolation are typically arrhythmic during the first few days of adult life and develop strong circadian rhythms by about a few days of age. In addition, average daily levels of period (per) mRNA in the brain are higher in foragers or forager-age bees (> 21 days of age) relative to young nest bees (approximately 7 days of age). The authors used social manipulations to uncouple behavioral rhythmicity, age, and task to determine the relationship between these factors and per. There was no obligate link between average daily levels of per brain mRNA and either behavioral rhythmicity or age. There also were no differences in per brain mRNA levels between nurse bees and foragers in social environments that promote precocious or reversed behavioral development. Nurses and other hive-age bees can have high or low levels of per mRNA levels in the brain, depending on the social environment, while foragers and foraging-age bees always have high levels. These findings suggest a link between honey bee foraging behavior and per up-regulation. Results also suggest task-related differences in the amplitude of per mRNA oscillation in the brain, with foragers having larger diurnal fluctuation in per than nurses, regardless of age. Taken together, these results suggest that social factors may exert potent influences on the regulation of clock genes.

Changes in period mRNA levels in the brain and division of labor in honey bee colonies.

Previous research showed that age-related division of labor in honey bees is associated with changes in activity rhythms; young adult bees perform hive tasks with no daily rhythms, whereas older bees forage with strong daily rhythms. We report that this division of labor is also associated with differences in both circadian rhythms and mRNA levels of period, a gene well known for its role in circadian rhythms. The level of period mRNA in the brain oscillated in bees of all ages, but was significantly higher at all times in foragers. Elevated period mRNA levels cannot be attributed exclusively to aging, because bees induced to forage precociously because of a change in social environment had levels similar to normal age foragers. These results extend the regulation of a "clock gene" to a social context and suggest that there are connections at the molecular level between division of labor and chronobiology in social insects.

Influence of arm positioning on rest/stress technetium-99m labeled sestamibi tomographic myocardial perfusion imaging.

BACKGROUND: Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is routinely performed with patients' arms positioned above their heads to avoid potential attenuation artifact and reduced image quality. Currently no data are available to support the use of this practice using 99mTc SPECT MPI: METHODS AND RESULTS: Forty-one patients referred for routine rest/stress MPI were imaged using the standard protocol with arms positioned above their heads and again with their arms at their sides. The patients were injected with 10 to 45 mCi (370 to 1665 MBq) of 99mTc-labeled sestamibi (99mTc-sestamibi), and SPECT images were acquired 30 to 90 minutes later. Thirty patients were imaged on an ADAC Vertex dual-head camera and 11 patients on an ADAC Cirrus single-head camera. Images were interpreted by 3 nuclear cardiologists without knowledge of patient identity, arm position, or camera type using a 17-segment scoring model. No significant differences were noted in the percentage of abnormal study results, reversibility extent, or location of MPI defects between the 2 arm positions in the same patients. Image quality was also similar. CONCLUSION: Arm positioning does not influence the interpretation of 99mTc-sestamibi SPECT myocardial perfusion imaging with regard to image quality or defect location and extent.

Lack of Activity of Docetaxel in Soft Tissue Sarcomas: Results of a Phase II Study of the Italian Group on Rare Tumors.

Purpose. The prognosis of advanced soft tissue sarcoma is poor, only a few drugs showing some activity with response rates around 15- 25%. Consequently drug development seems mandatory to improve treatment outcome. Following previous favourable EORTC experience, the Italian Group on Rare Tumors started a phase II study with docetaxel to confirm the activity of this drug in soft tissue sarcoma.Patients and methods. Thirty-seven patients with soft tissue sarcoma resistant to at least one anthracyclinecontaining regimen were enrolled in a phase II multicenter study evaluating docetaxel 100 mg/m(2) in a 1-h i.v. infusion q(3) weeks.Results.Thirty-seven patients were enrolled onto this phase II study and 36 were evaluable for response. Only one partial remission was observed [2.8% with 95% confidence interval (CI) 0.1- 16.2%]. Median progression-free and overall survival were 42 and 350 days, respectively. Neutropenia and leukopenia as well as cutaneous manifestations were the most common toxicities.Discussion. The results of this phase II study do not confirm a previous EORTC repor t on the activity of docetaxel in soft tissue sarcoma, but are consistent with other more recent phase II studies. The accumulated evidence does not justify the use of this drug in the management of patients suffering from this disease, resistant to anthracyclinecontaining regimens.

Isolation of seven unique biogenic amine receptor clones from the honey bee by library scanning.

The biogenic amine receptor genes constitute an ancient and highly divergent family within the larger superfamily of G-protein-coupled receptors. These receptors play a central role in modulating nerve cell activity and thus behaviour. Because the honey bee offers numerous advantages for behavioural studies we endeavoured to isolate as many members of this gene family as possible from the bee. We compared numerous approaches to gene isolation and found that PCR amplification from small subfractions of cDNA or genomic DNA libraries enabled us to isolate clones that are otherwise undetectable. In total we isolated seven biogenic amine receptor clones and identified five additional related sequences by low-stringency Southern hybridization. Two clones, AmBAR4 and AmBAR6, are 84% and 72% identical to the Drosophila 5-HT2 and D1b receptors, respectively, and probably represent orthologous genes. Phylogenetic analysis indicates that AmBAR5 clusters loosely with a variety of tyramine and octopamine receptors with which it shares <66% identity. The other four clones, AmBAR1, AmBAR2, AmBAR3 and AmBAR7, are weakly to moderately related (28-45% identical) to Drosophila dopaminergic or mammalian adrenergic receptors and probably represent receptors of these classes whose orthologues have not previously been isolated from any insect. The honey bee clones expand the size of the known insect biogenic amine receptor gene family to sixteen members. Therefore the size of the biogenic amine receptor gene family of insects approaches that of vertebrates. This is true despite the reduced behavioural and genetic complexity of the insects relative to vertebrate animals.

Inverted left atrial appendage mimicking a left atrial mass during mitral valve repair.

This case report describes the appearance of a new homogenous mass seen in the left atrium on intraoperative transesophageal echocardiography after mitral valve repair. This "mass" was the inverted left atrial appendage. Echocardiographers need to recognize normal variants, such as an inverted left atrial appendage, to avoid misdiagnosis.

Superiority of clear-visor safety hat to opaque-visor hat: an evaluation of upper visual-field obstruction.

Three subjects were used to compare superior visual-field threshold for 5 North American industry-standard opaque safety hard hats with a prototype clear translucent-visor safety hard hat and a no-hat baseline condition. Average maximum degrees of superior visual field was equivalent for the clear-visor safety hat and no-hat conditions (52.0 degrees versus 48.3 degrees) but the opaque-visor safety hats resulted in only 15.1 degrees. The opaque safety hats were worse than the clear-visor safety hat and no-hat conditions by, on the average, an order of 3. Analysis indicated that visual-field obstruction is a potential problem for wearers of opaque safety hats. Field research will be required to assess the extent of injuries caused by an impaired superior field of vision when wearing opaque-safety-hat visors. The potential positive effects of the clear-visor safety hat on reduction of accidents also must be determined.

Preoperative concomitant cisplatin/VP16 and radiotherapy in stage III non-small cell lung cancer.

PURPOSE: To evaluate the therapeutic effectiveness of a combined chemoradiotherapy program, followed by surgery in selected cases, in Stage III non-small cell lung cancer. METHODS AND MATERIALS: Between August 1988 and February 1990, 43 patients Staged IIIa-b (UICC 1987, 58% IIIb) have been treated with concomitant chemotherapy (cisplatin 15 mg/m2 and VP16 75 mg/m2, 5 days a week on week 1 and 5) and radiotherapy (40 Gy split course, 2 Gy/day on week 1, 2, 5, and 6), followed by attempted curative thoracotomy or more cycles of full dose chemotherapy with the same two drugs. RESULTS: Planned chemoradiotherapy has been given to 91% of patients; 13/43 patients have been operated, with 12 complete resections and three (7%) pathological complete responses. Toxicity was significant, with two postoperative deaths and two fatal radiation pneumonitis. Crude progression-free survival rate is 21% at 30 months, with nine patients (21%) alive and free from progression at follow-up times ranging from 31 to 49 months. Subset survival analysis showed a possibly greater therapeutic effect for non-squamous histology as compared to squamous carcinoma. CONCLUSION: These results are encouraging in a cohort of patients with quite advanced disease (58% Stage IIIb).

Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin.

At present, there is no effective medical therapy in metastatic nonsmall cell (NSC) lung cancer patients who progressed under a first-line chemotherapy containing cisplatin. Since recent data have demonstrated the antineoplastic properties and the lack of toxicity of the pineal hormone melatonin (MLT), a randomized study was designed to evaluate the influence of an MLT treatment (10 mg/day orally at 7.00 p.m.) on the survival time at 1 year from the progression under chemotherapy in respect to supportive care alone in a group of metastatic NSC lung cancer patients, who did not respond to a first-line chemotherapy containing cisplatin. The study includes 63 consecutive metastatic NSC lung cancer patients, who were randomized to receive MLT (n = 31) or supportive care alone (n = 32). The percentage of both stabilizations of disease and survival at 1 year was significantly higher in patients treated with MLT than in those treated only with supportive care. No drug-related toxicity was seen in patients treated with MLT, who, on the contrary, showed a significant improvement in performance status. This randomized study shows that the pineal hormone MLT may be successfully administered to prolong the survival time in metastatic NSC lung cancer patients who progressed under a first-line chemotherapy with cisplatin, for whom no other effective therapy is available up to now.

[Electrocardiographic and arterial pressure changes in the acute phase of subarachnoid hemorrhage]. / Modificari electrocardiografice si de tensiune arteriala în faza acuta a hemoragiei subarahnoidiene.

A prospective study was made of 30 patients, admitted to the neurology ward with subarachnoidal hemorrhage (SAH), at its onset. The diagnosis was established on the basis of anamnesis, clinical examination, spinal puncture, anatomopathological examination. The patients with other cerebrovascular affections or with antecedents of ischaemic cardiac affections were excluded. ECG tracings, serum ionogram, AT and VA at the onset and in evolution, and their modifications were followed and assessed in all the patients. The conclusion is reached that SAH in acute phase is associated with transitory ECG and pressure anomalies which become elements of unfavourable prognosis when persistent and deeply altered. They are valuable, at hand, elements in the differential diagnosis, and in the opportune therapeutical intervention.