A comprehensive study of the epidemiology of haematological malignancies in North Queensland.

BACKGROUND: There is an absence of clinically relevant epidemiological data in regional Australia pertaining to haematological malignancies. AIM: To determine the incidence and geographical variation of haematological malignancies in North Queensland using a clinically appropriate disease classification. METHODS: Retrospective, observational study of individual patient data records of all adults diagnosed with a haematological malignancy between 2005 and 2014 and residing within The Townsville Hospital Haematology catchment region. We report descriptive summaries, incidence rates and incidence-rate ratios of haematological malignancies by geographic regions. RESULTS: One thousand, five hundred and eighty-one haematological malignancies (69% lymphoid, 31% myeloid) were diagnosed over the 10-year study period. Descriptive data are presented for 58 major subtypes, as per the WHO diagnostic classification of tumours of haemopoietic and lymphoid tissues. The overall median age at diagnosis was 66 years with a male predominance (60%). We demonstrate a temporal increase in the incidence of haematological malignancies over the study period. We observed geographical variations in the age-standardised incidence rates per 100 000 ranging from 0.5 to 233.5. Our data suggest an increased incidence rate ratio for haematological malignancies in some postcodes within the Mackay area compared with other regions. CONCLUSION: The present study successfully reports on the incidence of haematological malignancies in regional Queensland using a clinically meaningful diagnostic classification system and identifies potential geographic hotspots. We advocate for such contemporary, comprehensive and clinically meaningful epidemiological data reporting of blood cancer diagnoses in wider Australia. Such an approach will have significant implications towards developing appropriate data-driven management strategies and public health responses for haematological malignancies.

A 14-year retrospective analysis of indications and outcomes of autologous haemopoietic stem cell transplantation in regional Queensland: a single-centre experience.

BACKGROUND: The Townsville Hospital is a tertiary hospital in North Queensland with one of the largest regional transplant centres in Australia, performing primarily autologous haemopoietic stem cell transplants (HSCT) for various haematological malignancies. AIMS: This single-centre, retrospective, observational study aims to describe the activity and outcomes of autologous HSCT at The Townsville Hospital between 2003 and 2017 to verify safety standards. METHODS: Patient-level data were collected, including demographics, frequency and indication for transplant, conditioning, current clinical status and cause of death. Key outcomes included overall survival, non-relapse mortality, incidence of therapy-related neoplasm and causes of death. Progression-free survival in the multiple myeloma (MM) subgroup was also assessed. RESULTS: There were 319 autologous HSCT in 286 patients, with a median age of 58 years (range 14-71 years); 62% of patients were male. Indications for transplantation were: MM 53.7%, non-Hodgkin lymphoma 29.4%, Hodgkin lymphoma 5.0% and other 11.9%. Causes of death were: disease progression/relapse (65.2%), second malignancy (17.0%), infection (9.8%) and other (8.0%). Non-relapse mortality was 1.2% (95% confidence interval 0.4-3.0) and 3.2% (1.7-5.7) at 100 days and 1 year, respectively, post-HSCT. Overall survival at 2 years was 81.0% (73.8-86.4) for MM and 69.6% (58.8-78.1) for non-Hodgkin lymphoma. The median progression-free survival in the MM cohort was 3.3 years. CONCLUSION: The Townsville Hospital transplant centre provides an important transplant service in regional Queensland, with outcomes comparable to national data. We reported a relatively high rate of second malignancy as a cause of death.

Simultaneous quantitative susceptibility mapping and Flutemetamol-PET suggests local correlation of iron and ß-amyloid as an indicator of cognitive performance at high age.

The accumulation of ß-amyloid plaques is a hallmark of Alzheimer's disease (AD), and recently published data suggest that increased brain iron burden may reflect pathologies that synergistically contribute to the development of cognitive dysfunction. While preclinical disease stages are considered most promising for therapeutic intervention, the link between emerging AD-pathology and earliest clinical symptoms remains largely unclear. In the current study we therefore investigated local correlations between iron and ß-amyloid plaques, and their possible association with cognitive performance in healthy older adults. 116 older adults (mean age 75 ±â€¯7.4 years) received neuropsychological testing to calculate a composite cognitive score of performance in episodic memory, executive functioning, attention, language and communication. All participants were scanned on a combined PET-MRI instrument and were administered T1-sequences for anatomical mapping, quantitative susceptibility mapping (QSM) for assessing iron, and 18F-Flutemetamol-PET for estimating ß-amyloid plaque load. Biological parametric mapping (BPM) was used to generate masks indicating voxels with significant (p < 0.05) correlation between susceptibility and 18F-Flutemetamol-SUVR. We found a bilateral pattern of clusters characterized by a statistical relationship between magnetic susceptibility and 18F-Flutemetamol-SUVR, indicating local correlations between iron and ß-amyloid plaque deposition. For two bilateral clusters, located in the frontal and temporal cortex, significant relationships (p<0.05) between local ß-amyloid and the composite cognitive performance score could be observed. No relationship between whole-cortex ß-amyloid plaque load and cognitive performance was observable. Our data suggest that the local correlation of ß-amyloid plaque load and iron deposition may provide relevant information regarding cognitive performance of healthy older adults. Further studies are needed to clarify pathological correlates of the local interaction of ß-amyloid, iron and other causes of altered magnetic susceptibility.

Comparison of Long-term Outcomes of Heparin Bonded Polytetrafluoroethylene and Autologous Vein Below Knee Femoropopliteal Bypasses in Patients with Critical Limb Ischaemia.

OBJECTIVE/BACKGROUND: Endovascular first is the preferred therapy approach to critical limb ischaemia (CLI). However, in spite of new endovascular techniques, bypass surgery still plays an important role, especially in patients with complex anatomy in whom endovascular therapy is not considered feasible, or has failed. The goal of this study was to analyse the outcomes of prosthetic or autologous vein for femoropopliteal (P3) bypasses performed under the abovementioned conditions. METHODS: A retrospective analysis of patients who underwent a femoropopliteal (P3) bypass for CLI (March 2007-December 2015) was conducted. Endovascular therapy was not possible. Patency rates, limb salvage, major adverse limb event (MALE) free survival, and survival after 5 years were analysed. RESULTS: In total, 151 cases were included in the analysis (rest pain 35.8%, ulcer/gangrene 64.3%). The graft material was autologous vein in 76 cases (vein group) and heparin bonded expanded polytetrafluoroethylene (HePTFE) in 75 cases (HePTFE group). Indications, risk factors, previous revascularisation procedures, and runoff vessels were similar in both groups. Thirty day mortality was 6.6% in the vein group and 5.3% in the HePTFE group (p = .508), early graft occlusion (6.6% vs. 5.3%; p = .508) and 30 day major amputation rate (0% vs. 2.7%; p = .245) were similar between the two groups. Overall primary patency was 51.7% (55.5% [vein group] vs. 51.7% [HePTFE group]; p = .897) and overall secondary patency was 64.2% (74.6% [vein group] vs. 55.6% [HePTFE group]; p = .119), all without significance after 5 years. However, limb salvage (79.1%) was significantly different (90.0% [vein group] vs. 62.9% [HePTFE group]; p = .021). Survival was similar between the groups (47.3% vs. 42.9%; p = .582) as well as MALE free survival (69.4% vs. 55.0%; p = .348). CONCLUSION: Bypasses to the below knee popliteal artery show good results in patients with CLI unsuitable for endovascular therapy. Vein is still the first line graft material.

Active sunscreen ingredients in Australia.

UV radiation exposure is the major contributor to photocarcinogenesis and photoageing. Reducing UV radiation exposure can be achieved by using adequate sunscreen preparations. The use of sunscreen can significantly reduce the incidence of squamous cell carcinoma, actinic keratoses and invasive melanoma. In the Australian market over 900 sunscreen products are available, each with their own brand, formulation and ingredients. It can be difficult for dermatologists and consumers to determine which are the most effective and appropriate products to use. We discuss the specific active ingredients found in sunscreen formulations available in Australia, their mode of protection, photostability, solubility, and side-effects and the methods used by the Therapeutic Goods Administration to determine the ratings and efficacy of each sunscreen.

A comparison of tibial and peroneal venous and HePTFE bypasses in diabetics with critical limb ischemia.

OBJECTIVE: In this study we analyzed the outcome of tibial and peroneal venous and heparin-bonded expanded polytetrafluoroethylene (HePTFE) bypasses in diabetics with critical limb ischemia (CLI). We aimed to verify our hypothesis that HePTFE grafts will achieve acceptable 1-year patency and limb salvage results in patients who lack an adequate vein. METHODS: We conducted a retrospective analysis for all diabetics who underwent tibial bypass surgery in our department between October 2007 and October 2012. The study includes 97 grafts. All these patients were not suited for an endovascular therapy. We used autologous veins in 56 cases (Vein-Group) and HePTFE grafts in 41 cases (HePTFE-Group). Study endpoints were primary and secondary patency, limb salvage, and survival at 2 years postoperatively. RESULTS: Risk factors and indications were similar in both groups. The comparison between HePTFE- and Vein-Group showed significantly different patency rates. At 2 years, primary patency was 39.3% in HePTFE-Group vs. 78.5% in Vein-Group (P = .003) and secondary patency was 47.4% vs. 81.9% (P = .002). Limb salvage at 2 years was 79.3% vs. 87.4% (P = .073) and survival was 64.6% vs. 62.9% (P = .593) at the 2-year mark, with no significant differences. 30-days mortality, graft occlusion and major amputation rate showed no significant differences, either. CONCLUSIONS: This study shows that HePTFE bypasses are a viable option for diabetics undergoing tibial bypass surgery when no adequate vein is available.

Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine.

The leishmaniases are a complex of vector-borne diseases caused by protozoan parasites of the genus Leishmania. LEISHDNAVAX is a multi-antigen, T-cell epitope-enriched DNA vaccine candidate against human leishmaniasis. The vaccine candidate has been proven immunogenic and showed prophylactic efficacy in preclinical studies. Here, we describe the safety testing of LEISHDNAVAX in naive mice and rats, complemented by the demonstration of tolerability in Leishmania-infected mice. Biodistribution and persistence were examined following single and repeated intradermal (i.d.) administration to rats. DNA vectors were distributed systemically but did not accumulate upon repeated injections. Although vector DNA was cleared from most other tissues within 60 days after the last injection, it persisted in skin at the site of injection and in draining lymph nodes. Evaluation of single-dose and repeated-dose toxicity of the vaccine candidate after i.d. administration to naive, non-infected mice did not reveal any safety concerns. LEISHDNAVAX was also well tolerated in Leishmania-infected mice. Taken together, our results substantiate a favorable safety profile of LEISHDNAVAX in both naive and infected animals and thus, support the initiation of clinical trials for both preventive and therapeutic applications of the vaccine.

Active vaccination with ankyrin G reduces ß-amyloid pathology in APP transgenic mice.

Serum antibodies against amyloid-ß peptide (Aß) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against the neuronal cytoskeletal protein ankyrin G (ankG); these correlated with slower rates of cognitive decline. Neuronal expression of ankG was higher in AD brains than in nondemented age-matched healthy control subjects. AnkG was present in exosomal vesicles, and it accumulated in ß-amyloid plaques. Active immunization with ankG of arcAß transgenic mice reduced brain ß-amyloid pathology and increased brain levels of soluble Aß(42). AnkG immunization induced a reduction in ß-amyloid pathology, also in Swedish transgenic mice(.) Anti-ankG monoclonal antibodies reduced Aß-induced loss of dendritic spines in hippocampal ArcAß organotypic cultures. Together, these data established a role for ankG in the human adaptive immune response against resident brain proteins, and they show that ankG immunization reduces brain ß-amyloid and its related neuropathology.

Chromosome-wide distribution of haplotype blocks and the role of recombination hot spots.

Recent studies of human populations suggest that the genome consists of chromosome segments that are ancestrally conserved ('haplotype blocks'; refs. 1-3) and have discrete boundaries defined by recombination hot spots. Using publicly available genetic markers, we have constructed a first-generation haplotype map of chromosome 19. As expected for this marker density, approximately one-third of the chromosome is encompassed within haplotype blocks. Evolutionary modeling of the data indicates that recombination hot spots are not required to explain most of the observed blocks, providing that marker ascertainment and the observed marker spacing are considered. In contrast, several long blocks are inconsistent with our evolutionary models, and different mechanisms could explain their origins.

Rational design of high performance surface plasmon resonance sensors based on two-dimensional metallic hole arrays.

We have rationally designed two-dimensional Au and Ag hole arrays for high performing surface plasmon resonance (SPR) sensing. The figure-of-merit (FOM), which is defined as sensitivity/linewidth, is found to be highly geometry-dependent. For sensitivity, we find it is equal to the period of array when exciting low order surface plasmon modes at low incident angle. Therefore, increasing period improves sensitivity. On the other hand, narrow linewidth can be obtained from small hole size so that the radiative decay loss is minimized. By using a pair of orthogonally oriented polarizer and analyzer, the signal-to-noise ratio (SNR) can be greatly enhanced due to the elimination of the nonresonant reflection background. As a proof of our strategy, we have obtained FOM larger than 100/RIU and SNR higher than 110 from Au arrays. Our results show the importance of understanding the basic properties of surface plasmon polaritons in order to systematically optimize the performance of the plasmonic system for a given application.

Impact of beta-amyloid-specific florbetaben PET imaging on confidence in early diagnosis of Alzheimer's disease.

BACKGROUND: Early diagnosis of Alzheimer's disease (AD) may be corroborated by imaging of beta-amyloid plaques using positron emission tomography (PET). Here, we performed an add-on questionnaire study to evaluate the relevance of florbetaben imaging (BAY 949172) in diagnosis and consecutive management of probable AD patients. METHODS: AD patients with a clinical diagnosis in accordance with the NINCDS-ADRDA criteria or controls were imaged using florbetaben. Referring physicians were asked on a voluntary basis about their confidence in initial diagnosis, significance of PET imaging results, and their anticipated consequences for future patient care. RESULTS: 121 questionnaires for probable AD patients and 80 questionnaires for controls were evaluated. In 18% of patients who had initially received the diagnosis of probable AD, PET scans were rated negative, whereas in controls 18% of scans were positive. An increase in confidence in the initial diagnosis was frequently reported (80%). Imaging results had a significant impact on the intended patient care, as judged by the referring physicians; this was most prominent in those patients with a contradicting scan and/or a low confidence in the initial diagnosis. CONCLUSION: Florbetaben amyloid imaging increases the overall confidence in diagnosis of AD and may frequently influence clinical decisions and patient management.

GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults.

BACKGROUND: Effects of beta-amyloid accumulation on neuronal function precede the clinical manifestation of Alzheimer's disease (AD) by years and affect distinct cognitive brain networks. As previous studies suggest a link between beta-amyloid and dysregulation of excitatory and inhibitory neurotransmitters, we aimed to investigate the impact of GABA and glutamate on beta-amyloid related functional connectivity. METHODS: 29 cognitively unimpaired old-aged adults (age = 70.03 ±â€¯5.77 years) were administered 11C-Pittsburgh Compound B (PiB) positron-emission tomography (PET), and MRI at 7 Tesla (7T) including blood oxygen level dependent (BOLD) functional MRI (fMRI) at rest for measuring static and dynamic functional connectivity. An advanced 7T MR spectroscopic imaging (MRSI) sequence based on the free induction decay acquisition localized by outer volume suppression' (FIDLOVS) technology was used for gray matter specific measures of GABA and glutamate in the posterior cingulate and precuneus (PCP) region. RESULTS: GABA and glutamate MR-spectra indicated significantly higher levels in gray matter than in white matter. A global effect of beta-amyloid on functional connectivity in the frontal, occipital and inferior temporal lobes was observable. Interactive effects of beta-amyloid with gray matter GABA displayed positive PCP connectivity to the frontomedial regions, and the interaction of beta-amyloid with gray matter glutamate indicated positive PCP connectivity to frontal and cerebellar regions. Furthermore, decreased whole-brain but increased fronto-occipital and temporo-parietal dynamic connectivity was found, when GABA interacted with regional beta-amyloid deposits in the amygdala, frontal lobe, hippocampus, insula and striatum. CONCLUSIONS: GABA, and less so glutamate, may moderate beta-amyloid related functional connectivity. Additional research is needed to better characterize their interaction and potential impact on AD.

Emerging Therapeutic Potential of Nanoparticles in Pancreatic Cancer: A Systematic Review of Clinical Trials.

Pancreatic cancer is an aggressive disease with a five year survival rate of less than 5%, which is associated with late presentation. In recent years, research into nanomedicine and the use of nanoparticles as therapeutic agents for cancers has increased. This article describes the latest developments in the use of nanoparticles, and evaluates the risks and benefits of nanoparticles as an emerging therapy for pancreatic cancer. The Preferred Reporting Items of Systematic Reviews and Meta-Analyses checklist was used. Studies were extracted by searching the Embase, MEDLINE, SCOPUS, Web of Science, and Cochrane Library databases from inception to 18 March 2016 with no language restrictions. Clinical trials involving the use of nanoparticles as a therapeutic or prognostic option in patients with pancreatic cancer were considered. Selected studies were evaluated using the Jadad score for randomised control trials and the Therapy CA Worksheet for intervention studies. Of the 210 articles found, 10 clinical trials including one randomised control trial and nine phase I/II clinical trials met the inclusion criteria and were analysed. These studies demonstrated that nanoparticles can be used in conjunction with chemotherapeutic agents increasing their efficacy whilst reducing their toxicity. Increased efficacy of treatment with nanoparticles may improve the clinical outcomes and quality of life in patients with pancreatic cancer, although the long-term side effects are yet to be defined. The study registration number is CRD42015020009.

Colocalization of cerebral iron with Amyloid beta in Mild Cognitive Impairment.

Quantitative Susceptibility Mapping (QSM) MRI at 7 Tesla and 11-Carbon Pittsburgh-Compound-B PET were used for investigating the relationship between brain iron and Amyloid beta (Aß) plaque-load in a context of increased risk for Alzheimer's disease (AD), as reflected by the Apolipoprotein E ε4 (APOE-e4) allele and mild cognitive impairment (MCI) in elderly subjects. Carriers of APOE-e4 with normal cognition had higher cortical Aß-plaque-load than non-carriers. In MCI an association between APOE-e4 and higher Aß-plaque-load was observable both for cortical and subcortical brain-regions. APOE-e4 and MCI was also associated with higher cortical iron. Moreover, cerebral iron significantly affected functional coupling, and was furthermore associated with increased Aß-plaque-load (R2-adjusted = 0.80, p < 0.001) and APOE-e4 carrier status (p < 0.001) in MCI. This study confirms earlier reports on an association between increased brain iron-burden and risk for neurocognitive dysfunction due to AD, and indicates that disease-progression is conferred by spatial colocalization of brain iron deposits with Aß-plaques.

Beneficial effects of tissue-type plasminogen activator in acute myocardial ischemia in cats.

Tissue-type plasminogen activator is a new thrombolytic agent that dissolves intravascular thrombi in coronary and peripheral vessels with less pronounced systemic lysis than that produced by streptokinase. Plasminogen activator was shown to induce reperfusion, and to salvage ischemic myocardium, by lysing experimentally induced coronary artery thrombi. The effect of a melanoma cell-derived tissue-type plasminogen activator was studied in cat myocardium rendered ischemic by coronary artery ligation for 2 hours and reperfused for another 4 hours. Plasminogen activator was infused at a rate of 500 IU X kg-1 X min-1 for the first 30 minutes of reperfusion. The marked increase in plasma creatine kinase activity during reperfusion was significantly lower in plasminogen activator-treated cats at 4, 5 and 6 hours, with 7.7 +/- 1.5 X 10(-3) IU X mg protein-1 (n = 8) in the plasminogen activator group versus 17.8 +/- 3.5 X 10(-3) IU X mg protein-1 (n = 7) in the vehicle group at 6 hours (mean +/- SEM). The area at risk in the two ischemic groups was not different, being 14.6 +/- 1.5 and 16.6 +/- 1.4% of total left ventricular mass for the treated and untreated groups, respectively. However, the mass of necrotic tissue determined histochemically was significantly lower in the plasminogen activator-treated group, accounting for 29.5 +/- 3.9% of the area at risk compared with 46.8 +/- 4.2% of area at risk in cats receiving only the vehicle (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Consensus paper of the WFSBP Task Force on Biological Markers of Dementia: the role of CSF and blood analysis in the early and differential diagnosis of dementia.

Aging of population, and increasing life expectancy result in an increasing number of patients with dementia. This symptom can be a part of a completely curable disease of the central nervous system (e.g, neuroinflammation), or a disease currently considered irreversible (e.g, Alzheimer's disease, AD). In the latter case, several potentially successful treatment approaches are being tested now, demanding reasonable standards of pre-mortem diagnosis. Cerebrospinal fluid and serum analysis (CSF/serum analysis), whereas routinely performed in neuroinflammatory diseases, still requires standardization to be used as an aid to the clinically based diagnosis of AD. Several AD-related CSF parameters (total tau, phosphorylated forms of tau, Abeta peptides, ApoE genotype, p97, etc.) tested separately or in a combination provide sensitivity and specificity in the range of 85%, the figure commonly expected from a good diagnostic tool. In this review, recently published reports regarding progress in neurochemical pre-mortem diagnosis of dementias are discussed with a focus on an early and differential diagnosis of AD. Novel perspectives offered by recently introduced technologies, e.g, fluorescence correlation spectroscopy (FCS) and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) are briefly discussed.

Peptide leukotriene receptor antagonism in myocardial ischaemia and reperfusion.

OBJECTIVE: The aim was to investigate the role of peptide leukotrienes in the pathophysiology of myocardial injury during reperfusion of previously ischaemic myocardium. METHODS: Adult male cats (2.9-5.4 kg) were subjected to left anterior descending coronary artery occlusion for 3 h followed by 3 h of reperfusion. The peptide leukotriene receptor antagonist, LY-171883, was given intravenously only during the reperfusion period (3 mg.kg-1 bolus; 3 mg.kg-1 x h-1 infusion). Ischaemic injury was assessed by nitroblue tetrazolium staining and tissue creatine kinase activity; neutrophil infiltration was determined by myeloperoxidase activity of myocardial homogenates. RESULTS: There was no significant difference at any time point in the experimental protocol between mean arterial blood pressure or pressure-rate index in cats given LY-171883 (3 mg.kg-1) and cats given vehicle. The area at risk of infarction (AAR) was 24(SEM 2)% for vehicle treated cats and 22(2)% for the drug treated cats. The necrotic area was 48(5)% of the AAR for the vehicle group but only 29(5)% of the AAR for the group given LY-171883 (p < 0.02). Left ventricular maximum +dP/dt tended to be higher with drug treatment compared to vehicle at the end of the reperfusion period. Tissue from the area at risk was assayed for creatine kinase activity and neutrophil specific myeloperoxidase activity as an index of the accumulation of neutrophils in this region. Creatine kinase activity was significantly higher (p < 0.05) in the AAR for drug nu vehicle treated cats following reperfusion, confirming the histochemical analysis. Myeloperoxidase activity increased approximately 12-fold in the AAR of cats receiving vehicle. LY-171883 did not reduce the myeloperoxidase activity significantly in the area at risk. CONCLUSIONS: LY-171883 has a protective effect in ischaemia-reperfusion injury to the myocardium. These findings suggest a role for peptide leukotrienes both in the extension of ischaemic damage and in post-ischaemic ventricular dysfunction during reperfusion.

The impact of infrainguinal endovascular interventions on the results of subsequent femoro-tibial bypass procedures: a retrospective cohort study.

BACKGROUND: Endovascular recanalization has become the accepted first-line treatment strategy for most lower extremity arterial occlusions, especially in patients with critical limb ischemia (Rutherford 4-6). Prior endovascular interventions have been described as risk factors for the outcome of subsequent lower extremity bypass surgery. The effect on subsequent tibial and peroneal bypasses is controversial. We analyzed the impact of prior endovascular lower extremity revascularization procedures on the short- and mid-term results of femoro-tibial and femoro-peroneal bypasses. METHODS: A retrospective analysis was conducted of all patients who had undergone tibial or peroneal bypass surgery after prior endovascular interventions (PEI-Group, n=40) of the same extremity in our department from October 2007 to October 2012. We compared this group with a group of patients who had received a tibial or peroneal bypass as primary revascularization procedure (BF-Group, n=93) during the same period of time because primary endovascular therapy had been deemed unfeasible in those cases. Indication in all cases was critical limb ischemia; the median age was 78 years (range 50-90 years), 45.1% were diabetics, and 42.9% were female. The graft material was autologous vein in 80 cases and HePTFE in 53 cases. Endpoints of the analysis were primary and secondary patency rates, limb salvage and survival at 2 years postoperatively. RESULTS: At 2 years overall primary patency was 68.4%, secondary patency was 69.5%, limb salvage was 83.6% and survival was 62.6%. Primary patency for the BF-Group was 74.3% vs. 55.1% for the PEI-Group (P=.310) at 2 years; secondary patency was 74.6% vs. 59.1% (P=.268). Prior endovascular intervention did not have any significant effects on limb salvage (83.7% vs. 83.6%; P=.470) or survival rates (61.0% vs. 65.0%; P=.258) at the 2-year mark, either. There were no significant differences in graft occlusion, death and major amputation rates within the first 30 postoperative days. Except for male gender, there were no significant differences in risk factors and indications between the two groups. CONCLUSIONS: Prior endovascular intervention of femoro-tibial vessels does not have a negative impact on the outcome of subsequent tibial or peroneal bypass surgery in patients with critical limb ischemia.

A rapid-cycling bipolar patient treated with long nights, bedrest, and light.

BACKGROUND: Stabilization of rapid-cycling bipolar disorder is extremely difficult. METHODS: A refractory bipolar I rapid-cycling patient on valproate was treated with long "nights" (extended sleep in darkness) and daytime light therapy. RESULTS: Rapid cycling immediately stopped on initiation of a 10 hour dark/rest period. This was extended to 14 hours (plus a self-selected 1 hour midday nap) without problems. Depression gradually improved when midday light therapy was added; near-euthymia was attained after light therapy was shifted to the morning. CONCLUSIONS: Nonpharmacological chronobiological treatments may be a means to interrupt rapid cycling.

Lateralization of the Bereitschaftspotential to the left hemisphere in patients with major depression.

Fourteen patients with major depression and 18 healthy subjects performed a Bereitschaftspotential (BP) paradigm, which required them to clench the right fist at self-paced intervals. The BP was calculated as the integrated negative amplitude from BP onset to movement onset. The latter was defined by recording the electromyogram (EMG) from the right forearm. To evaluate lateralization, the integrated BPs at C3, C4, P3, and P4 were analyzed. In depressives, a significant asymmetry of the BP to the left was found, whereas in normals the BP was nearly symmetrically distributed around the midline. Three patients were retested when clinically improved. At that time the asymmetry to the left hemisphere had nearly vanished. This asymmetry to the left hemisphere is interpreted as a cortical deactivation of the right cerebral hemisphere and seems to be a state marker of depression.