Trial protocol: a clustered, randomised, longitudinal, type 2 translational trial of alcohol consumption and alcohol-related harm among adolescents in Australia.

BACKGROUND: This cluster randomised control trial is designed to evaluate whether the Communities That Care intervention (CTC) is effective in reducing the proportion of secondary school age adolescents who use alcohol before the Australian legal purchasing age of 18 years. Secondary outcomes are other substance use and antisocial behaviours. Long term economic benefits of reduced alcohol use by adolescents for the community will also be assessed. METHODS: Fourteen communities and 14 other non-contiguous communities will be matched on socioeconomic status (SES), location, and size. One of each pair will be randomly allocated to the intervention in three Australian states (Victoria, Queensland and Western Australia). A longitudinal survey will recruit grade 8 and 10 students (M = 15 years old, N = 3500) in 2017 and conduct follow-up surveys in 2019 and 2021 (M = 19 years old). Municipal youth populations will also be monitored for trends in alcohol-harms using hospital and police administrative data. DISCUSSION: Community-led interventions that systematically and strategically implement evidence-based programs have been shown to be effective in producing population-level behaviour change, including reduced alcohol and drug use. We expect that the study will be associated with significant effects on alcohol use amongst adolescents because interventions adopted within communities will be based on evidence-based practices and target specific problems identified from surveys conducted within each community. TRIAL REGISTRATION: The trial was retrospectively registered in September, 2017 ( ACTRN12616001276448 ), as communities were selected prior to trial registration; however, participants were recruited after registration. Findings will be disseminated in peer-review journals and community fora.

Fenestrated Endovascular Aortic Aneurysm Repair as a First Line Treatment Option to Treat Short Necked, Juxtarenal, and Suprarenal Aneurysms.

OBJECTIVES: The outcomes of fenestrated endovascular aneurysm repair (FEVAR) as a first line strategy is reported. METHODS: All consecutive patients treated with FEVAR for short neck, juxtarenal, or suprarenal aortic aneurysms under the guidance of the senior author within the period January 2010 to December 2014 were included. Data were collected from a prospectively maintained database. Analyzed outcomes included technical success, defined by successful stent graft implantation with patent stented target vessels and no Type I/III endoleak, operative mortality and morbidity, target vessel patency, endoleak, re-intervention, and death. Survival, target vessel stent patency, and re-intervention during follow up were calculated by Kaplan-Meier analysis. RESULTS: A total of 281 patients (245 male, mean age 72.1 ± 7.7 years) were treated. The mean aneurysm diameter was 60.2 ± 9.3 mm and median proximal neck length 2 mm (range 0-10 mm). Technical success was 96.8% (272/281). Technical failure included one intra-operative death due to embolization and cardiac arrest, one open conversion due to iliac rupture, and seven target vessel complications. The thirty day mortality was 0.7% (2/281). Mean follow up was 21 ± 15.9 months. Estimated survival at 1 and 3 years was 94.7% ± 1.6% and 84.6% ± 3.0%, respectively. Estimated freedom from re-intervention at 1 and 3 years was 96.1% ± 1.4%, and 90% ± 2.7%. Estimated target vessel stent patency at 1 and 3 years was 98.6% ± 0.5%, and 98.1% ± 0.6%, respectively. Mean aneurysm sac diameter decreased from 60.2 ± 9.3 mm pre-operatively to 53.2 ± 12.8 mm (p < .001). CONCLUSIONS: FEVAR as a first line strategy was associated with high technical success and a low operative mortality rate. Efficacy and durability in the mid-term appear very good, with significant regression of aneurysm sac diameter, high target vessel patency, and acceptable rate of re-intervention.

[Results of endovascular repair of TAAA in the first 50  patients]. / Bericht über die ersten 50 endovaskulären thorako-abdominellen Behandlungen mit Seitenarmprothesen.

BACKGROUND: Developments with fenestrated and branched stent grafts have opened the way to treat complex aortic aneurysms involving the visceral arteries. First reports on endovascular treatment of thoracoabdominal aneurysms have demonstrated the feasibility of the technique. METHODS: A literature review and results of first 50  patients treated with a custom-made Zenith device with fixed branches are presented. Most of the patients were refused open surgery mainly for the extent of the disease combined with co-morbidity, which included in most patients a combination of several risk factors. Mean aneurysm size was 71 mm and extent of the aneurysm was type  I (n = 9), type  II (n = 13), type  III (n = 19), and type  IV (n = 9), respectively. RESULTS: Primary and primary assisted technical successes in our series were 88 % (44 / 50) and 92 % (46 / 50), respectively. One patient died on day  1 from an intraoperative aneurysm rupture. In two patients a renal artery was lost, one due to rupture and one due to malpositioning of the bridging stent graft. In a fourth patient, a celiac artery could not be catheterised and was lost. Finally, in two more patients, catheterisation of in total three renal arteries proved impossible. This was solved by a retrograde approach for two renal arteries via laparotomy in one patient, and a spleno-renal bypass in the other patient. Thirty-day mortality was 8 %. Estimated survival at 6  months, 1  year, and 2  years was 91.2 %, 79.8 %, and 69.7 %, respectively. Freedom of reintervention of all kinds at 1 and 2  years was 81.9 % and 73.7 %, respectively. CONCLUSION: Results of fully endovascular repair of thoracoabdominal aneurysms in a high-risk cohort are promising. A learning curve should be expected. Although longer term results need to be awaited, it is likely that endovascular repair of thoracoabdominal aneurysms will become a preferential treatment option for many patients in the future.

Hemispheric asymmetry in ocean change and the productivity of ecosystem sentinels.

Climate change and other human activities are causing profound effects on marine ecosystem productivity. We show that the breeding success of seabirds is tracking hemispheric differences in ocean warming and human impacts, with the strongest effects on fish-eating, surface-foraging species in the north. Hemispheric asymmetry suggests the need for ocean management at hemispheric scales. For the north, tactical, climate-based recovery plans for forage fish resources are needed to recover seabird breeding productivity. In the south, lower-magnitude change in seabird productivity presents opportunities for strategic management approaches such as large marine protected areas to sustain food webs and maintain predator productivity. Global monitoring of seabird productivity enables the detection of ecosystem change in remote regions and contributes to our understanding of marine climate impacts on ecosystems.

Proliferative capacity of mononuclear cells in the human lung.

In pulmonary sarcoidosis, a chronic granulomatous disorder with different stages of activity, the proliferative capacity of the alveolar mononuclear cells is unknown. To get a closer look at this proliferation we combined pulse labeling (by means of tritium thymidine incorporation and autoradiography) with an immunocytochemical staining assay. This assay revealed on one single slide simultaneously blue CD4+ lymphocytes, brown CD8+ lymphocytes and red macrophages. We were able to show that CD4+ as well as CD8+ lymphocytes were radiolabeled only in the active state of the disease. But macrophage proliferation occurred independently of the activity of the disease. In other words with this combination of techniques, it is possible to differentiate, on a single slide, three subsets of mononuclear cells, in combination with their proliferative behavior.

Effective-index increase, form birefringence and transition losses in UV-side-illuminated photosensitive fibers.

We present a simple variational method for the analysis of UV-side-illuminated single-mode fibers. We use a shiftable, two-dimensional elliptical Gaussian function as a field trial for the fundamental-mode. By this method, the actual UV-induced peak refractive-index increase can be quantitatively related to the measured effective-index increase. The asymmetry of the UV-induced refractive-index profile due to the absorption of the writing UV light causes both form birefringence and transition losses between UV-illuminated and non-illuminated fiber sections. These characteristics are easily calculated from the results of the variational method. We show that UV-illumination of the fiber from two opposite sides reduces both the form birefringence and the transition losses.

Loss of heterozygosity on chromosome arm 11q in lung carcinoids.

Neuroendocrine lung tumors such as typical carcinoid, atypical carcinoid, small-cell lung carcinoma, and large-cell neuroendocrine carcinoma represent a variable group with different biologic characteristics and unclear genetical relationships. We investigated the pattern of allelic loss on chromosome arm 11q in 20 sporadic carcinoid tumors of the lung using 10 microsatellite markers. Loss of heterozygosity was found in 13 of 20 tumors. In 5 of 9 typical carcinoids, 3 distinct regions of allelic loss were identified: 11q13.1 (D11S1883), 11q14.3-11q21 (D11S906), and 11q25 (D11S910). Atypical carcinoids showed loss of heterozygosity at 4 different regions: the first, most proximal region at 11q13 between markers PYGM and D11S937; the second at 11q14.3-11q21 (D11S906); and the third and fourth defined by markers D11S939 (11q23.2-23.3) and D11S910 (11q25). However, the region 11q13 harboring the MEN1 gene was more frequently affected in atypical carcinoids (7 of 11) than in typical carcinoids (2 of 9). The high rate of allelic losses within chromosomal region 11q13 in atypical carcinoids emphasizes the importance of this region for tumor development. We also recognized that more aggressive atypical carcinoids defined by high mitotic counts, vascular invasion, and/or organ metastasis are combined with increased allelic losses. HUM PATHOL 32:333-338.

Intrapleural instillation of rituximab for the treatment of malignant pleural effusions in NHL.

A patient with CD20(+) leukaemic lymphoplasmacytic Non-Hodgkin's lymphoma (NHL) presented with bilateral malignant pleural effusions. Systemic chemotherapy, repeated percutaneous drainage and bilateral continous chest tube drainage were unable to control the effusions. Rituximab was instilled in a dose-escalating manner via the chest tubes into both pleural spaces, within two weeks the effusions resolved, and the patient has stayed free of symptoms for eight months ongoing. Rituximab may be a promising novel treatment option for malignant effusions in CD20(+) NHL.

Self-expandable coated stent after intraluminal treatment of esophageal cancer: a risky procedure?

BACKGROUND: Stenting is a well established palliative treatment for stenotic malignant disease of the esophagus. Because of its merely mechanical potential other tumoricidal techniques are often done before stenting. METHODS: We did esophageal stenting in 11 patients (9 men and 2 women) using a self-expanding coated stent system. Three tumors were localized in the proximal, four in the middle, and four in the distal third of the esophagus. In 9 patients tumors were locally or functional nonresectable, 1 patient refused an operation, and 1 had a recurrence after esophagojejunostomy. One patient had had pretreatment by repetitive dilatation and local hyperthermia, 9 had had photodynamic therapy followed by endoluminal iridium 192 high-dose rate brachyradiotherapy, and 1 patient was admitted with esophagotracheal fistula. The interval between the last endoluminal treatment and stent insertion was between 3 and 29 days (mean, 11 days). RESULTS: In 7 patients (63.7%) no complications were observed. Four patients (36.3%) died of major complications within 1 week. Postmortem examination confirmed that the pressure of the fully expanding stent to the esophageal wall caused the rupture. CONCLUSION: The use of self-expanding coated stents in pretreated esophageal tumors is associated with a high risk of perforation due to pressure of the indwelling tube in a less resistant esophageal wall.

Testing of sunset yellow and orange II for genotoxicity in different laboratory animal species.

The azo dyes Sunset Yellow and Orange II were gavaged to rodent species to check bile, urine, and fecal extracts for possible mutagenic activity in the Ames test or in bone marrow cells for clastogenicity using cytogenetic test systems. After oral application the dyes showed a negative response in bile, excrements, and bone marrow. When an exogenous metabolic activation was performed, increased revertant numbers using Salmonella strain TA100 were obtained only in fecal extracts of Sunset Yellow-treated animals. It is concluded that no genotoxic harm is to be expected from the ingestion of Sunset-Yellow or Orange II.

Chromosome studies on bone marrow cells of Chinese hamsters fed a radiosterilized diet.

Metaphase preparations of chromosomes from bone marrow cells of Chinese hamsters were examined for mutagenic effects following the feeding of a radiosterilized diet. No increase in the incidence of structural chromosomal aberrations was observed. As far as numerical aberrrations were concerned, the proportion of cells with polyploidy increased to between 4 to 5 times the control level, irrespective of the moisture content of the diet. This polyploidy effect occurred very early, being detectable within 24 h, if the diet fed had been irradiated with an absorbed dose of 4.5 - 10(6) rad. The incidence of polyploidy remained below 0.5%, however, nor did it rise with higher radiation doses. When the feeding of the irradiated diet was stopped, the proportion of polyploid cells returned to the control level within a maximum of 6 weeks. If the diet was stored (initially) for 6 weeks following irradiation before being fed to the animals no increase in the number of polyploid cells was noted. These results are not interpreted as a mutagenic effect of the irradiated diet.

Mutagenicity testing of quinine with submammalian and mammalian systems.

Quinine hydrochloride was assayed for genotoxic activity by using 4 different test systems with distinct genetic endpoints. No indications for point mutations were observed in the Ames system. In 3 cytogenetic tests performed on small rodents, Chinese hamsters showed no genotoxic activity, while inbred strains of mice revealed a dose dependent increase of SCEs, enhanced incidence of micronuclei and elevated chromatid breaks.

Mutagenic evaluation of single cell protein with various mammalian test systems.

Single cell protein (SCP)--a product containing 80% raw protein obtained from bacteria grown on a methanol substrate--was tested for mutagenicity in 5 in vivo tests in different mammalian species. The animals were fed either a standard laboratory diet, a semi-synthetic diet, diets containing 12.5 and 25% SCP or pure SCP. The following investigations were carried out: dominant-lethal-test; host-mediated assay; micronucleus test; chromosome studies in bone marrow cells; in vivo sister chromatid exchange test. The statistical evaluation of all test results did not reveal any evidence for mutagenic activity of the SCP.

The anticlastogenic potential of fatty acid methyl esters.

To test for possible anticlastogenic effects of fatty acids, the methyl esters of fatty acids--short-chain to long-chain--were examined on busulfan in Chinese hamster bone-marrow cells using the chromosome aberration test. When the experimental animals were treated with fatty acid esters and the mutagen, the chromosome-breaking actions of busulfan were not modulated by the short-chain fatty acids, but the fatty acids from lauric acid (C12) up to nonadecanoic acid (C19) reduced the rate of aberrant metaphases from 9.4 to about 3% at doses of 100 mg/kg and less. Other chemical properties of the fatty acids (saturated or not, number of double bonds, even- or odd-numbered) had no influence on the anticlastogenic effects. The only exceptions to this rule were arachidonic acid, which had no effect, and gamma-linolenic acid, which had no consistent effect on the action of busulfan.

Antimutagenic effect of an antioxidant in mammals.

To test a possible antimutagenic activity of ethoxyquin (EQ) in bone-marrow cells, 3 cytogenetic tests with distinct genetic end-points were applied. Cyclophosphamide (CPA), serving as test mutagen, and the antioxidant EQ were administered immediately following each other to Chinese hamsters by stomach tube. Whereas the CPA dose was the same in each test, the EQ doses were increased up to a ratio of CPA/EQ = 1:25, in some cases up to 1:50. The formation of SCEs induced by CPA was not influenced by EQ--even at the highest dose. In the micronucleus test, however, EQ drastically reduced the micronucleus rate even at the lowest dose applied (20 mg/kg) and abolished the CPA effects at a dose of 100 mg/kg. This action of EQ against CPA was also found in the rat and mouse in the micronucleus test system. Two inbred strains of mouse showed similar reactions, but the induced micronucleus rate was higher and its decrease in response to increasing doses of EQ was more delayed. In the chromosome aberration test, EQ also showed a distinct anticlastogenic response. At higher EQ doses, all CPA-induced chromosomal damage was reduced down to the level of spontaneous rates. The anticlastogenic effect of EQ was quantitatively similar in the micronucleus and chromosome aberration tests. Only minor qualitative differences were recognizable.

In vivo effects of single or combined dietary antimutagens on mutagen-induced chromosomal aberrations.

The food components chlorophyllin, beta-carotene and alpha-linolenic acid (in its methyl ester form) were tested in Chinese hamsters for antimutagenic activity on the powerful mutagen thio-tepa. Each of these natural protective compounds inhibited by 70-85% the clastogenic effects induced by the mutagen. When 2 or 3 of these antimutagens were administered simultaneously no additive effects were observed. alpha-Linolenic acid methyl ester was the most effective antimutagen under the experimental conditions.

Anticlastogenic effect of beta-carotene in Chinese hamsters. Time and dose response studies with different mutagens.

beta-Carotene exhibited dose-dependent anticlastogenic effects on aberrations induced by the direct-acting mutagens thio-TEPA, methyl methanesulfonate and busulfan in the in vivo chromosome aberration test (bone marrow cells, Chinese hamsters). No effect was seen when retinol was used. Apparent differences in the action of beta-carotene on aberrations induced by the three applied mutagens may be due to differences in the solubility of the compounds and to the different routes of administration.

Mutagenicity of sulphonylureas.

The 11 derivatives of beta-cytotropic sulphonylureas commonly used in the treatment of diabetes mellitus were tested in vivo in the highly sensitive sister-chromatid exchange test. Chlorpropamide and tolbutamide gave a positive reaction with a clear dose-response in Chinese hamsters and mice. The two compounds gave a mutagenic response neither in the Salmonella/mammalian-microsome mutagenicity test (with and without microsomal activation) nor in the chromosomal aberration test. In the micronucleus test, chlorpropamide was positive in 3 strains of mouse, tolbutamide in one strain. In Chinese hamsters and in rats the micronucleus test was negative with both compounds.

Antimutagenic effects on male germ cells of mice.

The alkylating agent cyclophosphamide (CPA) and the antioxidant ethoxyquin (EQ) were administered perorally to NMRI mice. The strong clastogenic action of CPA on spermatogonia was diminished by simultaneous doses of EQ. Higher doses of the antioxidant produced greater anticlastogenic action. Furthermore, the action of the mutagen and the antioxidant on the late spermatids and the spermatozoa was observed using the dominant lethal test. The antioxidant had only a weak influence on these postmeiotic stages.