Predicting the Influence of Streamflow on Migration and Spawning of a Threatened Diadromous Fish, the Australian Grayling Prototroctes Maraena.

The development of effective strategies to restore the biological functioning of aquatic ecosystems with altered flow regimes requires a detailed understanding of flow-ecology requirements, which is unfortunately lacking in many cases. By understanding the flow conditions required to initiate critical life history events such as migration and spawning, it is possible to mitigate the threats posed by regulated river flow by providing targeted environmental flow releases from impoundments. In this study, we examined the influence of hydrological variables (e.g., flow magnitude), temporal variables (e.g., day of year) and spatial variables (e.g., longitudinal position of fish) on two key life history events (migration to spawning grounds and spawning activity) for a threatened diadromous fish (Australian grayling Prototroctes maraena) using data collected from 2008 to 2015 in the Bunyip-Tarago river system in Victoria. Our analyses revealed that flow changes act as a cue to downstream migration, but movement responses differed spatially: fish in the upper catchment showed a more specific requirement for rising discharge to initiate migration than fish in the lower catchment. Egg concentrations peaked in May when weekly flows increased relative to the median flow during a given spawning period. This information has recently been incorporated into the development of targeted environmental flows to facilitate migration and spawning by Australian grayling in the Bunyip-Tarago river system and other coastal systems in Victoria.

Influence of streamflow on spawning-related movements of golden perch Macquaria ambigua in south-eastern Australia.

In this study, linkages were examined between movement and spawning behaviour for golden perch Macquaria ambigua in a lowland river by integrating acoustic telemetry and egg and larval drift sampling over 4 years. Movement was strongly seasonal, being most prevalent during the spawning season (spring to early summer), and occurred primarily downstream into the lower river reaches during elevated flows. A very strong association was found between the occurrence of spawning and long-distance M. ambigua movement. The results also revealed that targeted environmental water allocation can promote movement and spawning of this species. By integrating multiple analytical approaches and focusing on key life-history events, this study provides an improved picture of the life history and flow requirements of M. ambigua. The findings can help guide the development of effective environmental flow recommendations.

OS023. Postpartum cardiovascular disease risk factors in women with ahistory of early onset preeclampsia, late onset preeclampsia and pregnancy induced hypertension.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in women. Epidemiological studies have shown an increased risk of a CVD event in women who have had a hypertensive disorder in one of their previous pregnancies. These data also suggest that these increased risks are associated with severity and time of onset of pre-eclampsia. Risk factors for CVD have not yet been compared between women who experienced early versus late and mild versus severe hypertensive disorders of pregnancy. OBJECTIVES: In this study we compared classic CVD risk factors of postpartum women with previous early-onset preeclampsia (EOPE), late onset pre-eclampsia (LOPE) and pregnancy induced hypertension (PIH). METHODS: A total of 81 women with previous EOPE (delivery required ⩽34weeks), 76 with LOPE (delivery ⩾36weeks) and 229 with PIH were included along with 79 healthy controls. Statistical analyses were performed using generalized linear models in PASW statistics 17.0, SPSS Inc. RESULTS: Adjusted means of blood pressure, fasting plasma glucose levels and LDL levels were significantly increased after all hypertensive disorders of pregnancy compared to controls. This increase of CVD risk factors was significantly correlated with severity and time of onset of the disease (Table 1). The prevalence of metabolic syndrome (BMI>30kg/m(2) and ⩾2 of the following; triglycerides ⩾150mg/dl, HDL cholesterol ⩾50mg/dl, systolic blood pressure ⩾130 or diastolic blood pressure ⩾85 and fasting plasma glucose levels ⩾100mg/dl) did not differ between the study groups; women who had PIH had the highest number of components of the metabolic syndrome (). CONCLUSION: These results further establish the predisposition to CVD in women with previous pre-eclampsia or PIH. EOPE is associated with a more pronounced CVD risk factor profile than LOPE or PIH, which may explain the previously described higher CVD event risk.

[Treatment of chronic pain in the internist's practice]. / Therapie chronischer Schmerzen in der internistischen Praxis.

Chronic pain is one of the most frequent complaints in outclinic supply. Careful anamnesis and physical examination are in the focus of diagnostic procedure. Their results will give strong evidence for the underlying pathogenesis. Nevertheless, the perception of pain remains completely subjective and can be only measured by asking the patient. Therefore, a multitude of validated instruments has been developed ranging from the simple intensity rating scales up to sophisticated questionnaires. Both, the diagnostic and therapeutic procedures should adhere to the bio-psycho-social concept of pain. Medical treatment should be executed in accordance to the WHO Guidelines for Cancer Pain Treatment. But for the majority of patients, multidisciplinary concepts are required including psychotherapy and iatrophysics.

[Early and late complications of chemotherapy of solid tumors]. / Akut- und Spätkomplikationen der Chemotherapie. Nebenwirkungen sind so individuell wie lhre Patienten

Treatment with cytostatic agents is associated with both acute side effects such as nausea, emesis, blood count changes, and allergic reactions, and late complications such as cardiac, renal or gastrointestinal toxicity. In addition to differences in substance groups, intra-individual variations on the part of patients, and their general and nutritional status, are of particular importance for the severity of such side effects. For improved treatment monitoring, side effects should be recorded and documented in accordance with common toxicity criteria. In view of the complexity of oncological treatment, including the optimal supporting measures, such treatments should remain in the hands of oncological specialists.

Inactivation of Bacillus subtilis spores and formation of bromate during ozonation.

Inactivation of B. subtilis spores with ozone was investigated to assess the effect of pH and temperature, to compare the kinetics to those for the inactivation of C. parvum oocysts, to investigate bromate formation under 2-log inactivation conditions, and to assess the need for bromate control strategies. The rate of B. subtilis inactivation with ozone was independent of pH, decreased with temperature (activation energy of 42,100 Jmol(-1)), and was consistent with the CT concept. B. subtilis was found to be a good indicator for C. parvum at 20-30 degrees C, but at lower temperatures B. subtilis was inactivated more readily than C. parvum. Bromate formation increased as both pH and temperature increased. For water with an initial bromide concentration of 33 microgl(-1), achieving 2-logs of inactivation, without exceeding the 100 microg l(-1) bromate standard, was most difficult at 30 degrees C for B. subtilis and at midrange temperatures (10-20 degrees C) for C. partum. pH depression and ammonia addition were found to reduce bromate formation without affecting B. subtilis inactivation, and may be necessary for waters containing more than 50 microgl(-1) bromide.

Identification of recurrent and novel mutations in the LDL receptor gene in German patients with familial hypercholesterolemia.

In order to identify mutations in the low density lipoprotein receptor (LDLR) gene in primary hypercholesterolemia, we screened 100 unrelated German individuals with elevated plasma LDL-C (LDL-C > 4,7 mmol/l) for mutations in the 18 exons and their flanking intronic sequences including the promoter region of the LDL-R gene using a combination of polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE) and direct sequencing. In addition we tested all patients for the presence of mutations in codons 3456 - 3553 of the gene encoding apolipoprotein B-100. In 56 individuals we detected 37 different mutations affecting the LDL-R gene, 16 of which, designated C122R, C127Y, C163W, F179L, R236W, E296X, R553C, V618D, T721I, V785D, G1358+2A, 257delTCTGGAGGT, 657delC, 676insACGGTATGGACTGCAdelGACG, C1205delTCT, 2420delTCCTTCT, have not yet been reported. One proband was a compound heterozygote showing two separate sequence variations (E207X and T705I). Seven patients were heterozygous for the mutation R3500Q within the apoB-100 gene. These results demonstrate that there is a broad spectrum of mutations in the LDL-R gene and that the R3500Q mutation is a frequent cause of hypercholesterolemia in the German population.

ABC transporter-mediated uptake of iron, siderophores, heme and vitamin B12.

Microbes have developed a number of different strategies to utilize iron, which is a vital element for most organisms but not always readily available from the environment. Based on experimental studies and sequence analysis data, this article gives a short overview of ABC transporters related to iron uptake: components of three distinct families mediate the translocation of iron, siderophores, heme and vitamin B12 across the cytoplasmic membrane of bacteria.

[60-year-old patient with fever, jaundice and intra-abdominal lymphomas]. / 60-jährige Patientin mit Fieber, Ikterus und intraabdominellen Lymphomen.

BACKGROUND: Infectious mononucleosis usually manifests in adolescents and young adults. Medical history in elderly patients is often atypical and severe. CASE REPORT: We report on the medical history of a 60-year-old woman, who came into our hospital with fever, icterus, decreasing performance status and abdominal pain. Splenomegaly and multiple abdominal lymph nodes could be found by ultrasound and CT scan. Endoscopically severe mucosal alterations could be found in the upper and lower gastrointestinal tract. Serologically, an acute EBV infection was diagnosed. With symptomatic treatment, the clinical course was without any problems. CONCLUSION: Casuistically, we described the atypical medical history of an elderly patient with infectious mononucleosis. In each undefined lymphadenopathy of elderly patients, an EBV infection should be included into the differential diagnosis.

Apolipoprotein E1 Baden (Arg(180)-->Cys). A new apolipoprotein E variant associated with hypertriglyceridemia.

Apolipoprotein (apo) E mediates the removal of chylomicron and very low density lipoprotein remnants from plasma. It is polymorphic in sequence and the products of the three common alleles (epsilon 2, epsilon 3, epsilon 4) differ from one another in their binding to lipoprotein receptors. ApoE2 is defective in binding and homozygosity for apoE2 is associated with type III hyperlipoproteinemia (HLP). Other rare isoforms of apoE have been found to be associated either with dominant type III HLP or with the development of hypertriglyceridemia. We identified a 42 year-old hypertriglyceridemic woman with an apoE phenotype 3/1. Restriction isotyping using AflIII/HaeII resulted in an apparent apoE genotype 3/2, suggesting that the mutation occurred in an epsilon 2 allele. DNA sequence analysis revealed a C-->T point mutation at the first position of the codon for amino acid residue 180 of the mature apoE. This predicted a change Arg(180)-->Cys. The mutation altered a recognition site for the endonuclease HaeII, which allowed us rapidly to screen for this mutation. In relatives of the proband, apoE1 Baden was consistently associated with hypertriglyceridemia. Similar to other apoE variants linked to hypertriglyceridemia, the Arg(180)-->Cys mutation is located within the lipid binding domain of apoE. We therefore suggest that apoE1 Baden may cause hypertrigylceridemia, possibly by inhibiting the hydrolysis of triglycerides associated with very low density lipoproteins.

[Chemotherapy in colorectal carcinoma. From "one-drug-show" to therapeutic multiplicity]. / Chemotherapie beim kolorektalen Karzinom. Von der "One-drug-Show" zur therapeutischen Vielfalt.

Over the past decade, the chemotherapeutic options in the treatment of colorectal carcinoma have improved considerably. Up into the nineties, chemotherapy for this condition was purely a "one-drug show", while, today, a range of effective substances and combinations are available, and these have considerably improved the prognosis of this tumour entity. Both the first and second line treatments are today firmly established. Determination of the most appropriate sequence and combination of these new drugs (primary combination therapy, sequential administration of the substances, etc.) is the subject of ongoing and planned future studies.

[Infusiontherapy with 5-fluorouracil ("infusional" 5-FU) in solid tumors]. / Infusionstherapien mit 5-Fluorouracil ("infusional" 5-FU) bei soliden Tumoren.

BACKGROUND: 5-FU is an important anticancer agent for many tumor entities. Because of the historical development of this compound it was predominantly administered as a bolus application, although it was well known that the antineoplastic activity of this antimetabolite is improved by prolonged administration schedules (protracted infusion ["infusional"] of 5-FU). Since port-a-cath systems and portable pumps became available, "infusional" 5-FU containing chemotherapies were intensively investigated in various tumors known to be susceptible to 5-FU. INDICATIONS: The largest experience with "infusional" 5-FU +/- folinic acid +/- other cytostatic drugs exists in gastrointestinal tumors. Meanwhile this way of 5-FU application is well established in the first- and second-line chemotherapy of metastatic colorectal and gastric cancer where it contributes to a clinically relevant improvement of the prognosis of these tumors. Other tumor entities where "infusional" 5-FU-based chemotherapies showed first positive results are i.e. breast cancer and esophageal cancers.

HDL steady state levels are not affected, but HDL apoA-I turnover is enhanced by Lifibrol in patients with hypercholesterolemia and mixed hyperlipidemia.

Lifibrol (4-(4'-tert-butylphenyl)-1-(4'carboxyphenoxy)-2-butanol) is a new hypocholesterolemic drug effectively reducing total cholesterol, LDL cholesterol, and apolipoprotein (apo) B in experimental animals and in humans. In contrast to fibrates and HMG-CoA reductase inhibitors the cholesterol and triglyceride lowering effect of Lifibrol is not accompanied by increases in HDL cholesterol and apoA-I levels. We examined the impact of Lifibrol on the metabolism of HDL apoA-I in patients with hyperlipoproteinemia, using endogenous labeling with stable isotopes. Kinetic studies were performed in five male hypercholesterolemic individuals (type IIa), before and on treatment with 450 mg of Lifibrol daily for 4 weeks and in five male individuals suffering from mixed hyperlipidemia (type IIb), before and on therapy, for 12 weeks. Lifibrol reduced total cholesterol by 14% (P=0.02) and LDL cholesterol by 16% (P=0. 014) in all patients, and decreased triglycerides by 34% in type IIb patients. During Lifibrol therapy, HDL cholesterol and ApoA-I concentrations did not change. Tracer kinetics revealed that the fractional catabolic rate (FCR) of HDL apoA-I increased by 22% (P=0. 013). This increase in the apoA-I FCR was accompanied by a 23% increase in HDL apoA-I production rate (P=0.006). We conclude that Lifibrol, although not changing HDL steady state concentrations, enhances the turnover of apoA-I containing HDL particles.

Analysis of the new indirect revascularization method by determining objective parameters of clinical chemistry, histo-chemistry and histology.

OBJECTIVE: This experimental study was initiated to determine whether transmyocardial laser revascularization (TMLR) after acute myocardial ischemia may improve clinical chemistry and diminish the amount of necrosis. In addition, the influence of TMLR on healthy myocardium was analyzed. METHODS: The prolonged short-term effectiveness of TMLR was evaluated in 44 open-chest anesthetized pigs with (n = 21) or without (n = 23) the setting of acute myocardial ischemia (observation period 6 h): seven pigs served as controls (thoracotomy only). An additional seven pigs had left anterior descending artery (LAD) occlusion only (ischemia group). A subsequent 14 pigs were treated by TMLR (CO2) prior to LAD occlusion: Seven pigs received one laser channel/cm2 (group 1) and in seven pigs two channels/cm2 in the LAD territory (group 2) were performed. In addition, 16 pigs underwent TMLR without ischemia: Eight pigs received one channel/cm2 (group 3) and eight pigs two channels/cm2 (group 4). Clinical chemistry, histo-chemical assessment and histology were performed. RESULTS: TMLR limits the expansion of the myocardial infarction zone: laser group 2 indicated a significant smaller area of necrosis in the area at risk (ischemic group (31%) vs. laser group 1 (19%), P = ns; laser group 2 (7%) vs. ischemic group, P < 0.01; laser group 1 vs. 2, P < 0.01). The amount of the area of necrosis and ischemia of laser groups 3 and 4 compared with control did not differ significantly (P = ns). Preventive creation of microchannels before ischemia did not diminish ischemic parameters (P = ns). The myocardial water content-measurements (MWC) in the ischemia, laser 1 and 2 groups did not show any difference at the end of the experiment, except higher values of laser group 2 (P < 0.05). Laser groups 3 and 4 revealed significantly higher MWC values compared with control (P < 0.001). CONCLUSIONS: This prolonged acute study demonstrates that CO2-TMLR significantly reduces the amount of necrosis in the area at risk, but does not reduce cardiac ischemic markers. In healthy myocardium, TMLR significantly increases myocardial water content and ischemic parameters and induces small ischemic and very small necrotic areas surrounding open laser channels. Generally, the elevated cardiac enzymes and proteins are mainly attributed to the expected rise caused by vaporization of myocardial tissue in all laser groups.

Lifibrol enhances the low density lipoprotein apolipoprotein B-100 turnover in patients with hypercholesterolemia and mixed hyperlipidemia.

Lifibrol (4-(4'-tert-butylphenyl)-1-(4'carboxyphenoxy)-2-butanol), a new hypocholesterolemic drug, effectively reduces total cholesterol (CH), low density lipoprotein (LDL)-CH, and apolipoprotein (apo) B in experimental animals and in humans. The impact of Lifibrol on the metabolism of apoB-100 containing lipoproteins in patients with hyperlipoproteinemia using endogenous labeling with stable isotopes is examined. Kinetic studies were performed in four male hypercholesterolemic individuals (type IIa) before and on treatment with 450 mg of Lifibrol daily for 4 weeks, and in five male individuals suffering from mixed hyperlipidemia (type IIb) before and on therapy for 12 weeks. Kinetic parameters were estimated by multicompartmental modeling. Lifibrol therapy reduced total CH by 16% (P = 0.012) in all patients, increased triglycerides (TG) by 11% (not significant) in type IIa patients and decreased TG by 34% (P = 0.059) in type IIb patients. During Lifibrol therapy, LDL apoB-100 concentrations decreased by 19% (P = 0.011) in all patients. The decrease in LDL apoB concentrations with Lifibrol therapy was due to an overall increase (75%, P = 0.006) of the fractional catabolic rates (FCR) of LDL apoB. This increase was partially attenuated by a 33% increase in LDL apoB production rate (PR) (P = 0.041). The overall production of apoB increased only slightly. Our data suggest that the major mechanism by which Lifibrol lowers LDL-CH is an increase in receptor-mediated catabolism of LDL rather than a decrease in hepatic apoB production.

Transport activity of FhuA, FhuC, FhuD, and FhuB derivatives in a system free of polar effects, and stoichiometry of components involved in ferrichrome uptake.

The Escherichia coli fhu operon, composed of the fhuA, C, D, and B genes, is essential for the utilization of ferric siderophores of the hydroxamate type and for the uptake of the antibiotic albomycin. We have had difficulty studying the effects of missense mutations in individual plasmid-encoded transport genes because appropriate test strains were not found: all isolated chromosomal mutations in either one of the fhu genes (with a complete loss of function) negatively influenced the expression of other fhu genes in the operon. In order to analyze Fhu mutant proteins in a system free of polar effects, we constructed a plasmid-encoded gene cassette system by introducing unique restriction sites that allowed precise cloning of individual fhu genes. The fhu cassette operon expressed in a chromosomal fhu deletion mutant enabled us to evaluate the transport activity of mutated FhuA, FhuC, FhuD or FhuB derivatives. In addition, we found that transport across the outer membrane (via FhuA, TonB, ExbB, D) rather than transport across the cytoplasmic membrane (via FhuC, D, B) was rate limiting. The stoichiometry of the components involved in the uptake of iron(III) hydroxamates seems to be important for proper functioning.

Effects of chronic angiotensin-converting enzyme inhibition on left ventricular and myocyte structure and function during recovery from chronic rapid pacing.

LV and myocyte function and angiotensin converting enzyme (ACE) activity with ACE inhibitor (ACEI) treatment were examined in four groups of dogs (n = 6 each): (1) control; (2) with 4 weeks of recovery from chronic rapid pacing (REC: 216 beats/min), (3) ACEI for the first 14 days of REC (ACEI--14), and (4) ACEI for 28 days of REC (ACEI--28). Three additional control dogs were administered ACEI for 28 days. LV mass increased with REC compared to control (146 +/- 6 v 92 +/- 3 g, P < 0.05), was unaffected with ACEI--14, and was decreased with ACEI--28 compared to REC (111 +/- 8 g, P < 0.05). Myocyte function was decreased in REC compared to controls (43 +/- 3 v 63 +/- 3 microns/s, P < 0.05) and was similarly reduced with ACEI--14. However, with ACEI--28, myocyte shortening velocity was increased compared to REC (56 +/- 1 microns/s, P < 0.05). Myocyte beta-adrenergic response was decreased with REC and ACEI--14 compared to controls (53 +/- 9 and 57 +/- 14, respectively v 127 +/- 14 microns/s, P < 0.05). ACEI--28 resulted in a normalization of myocyte beta-adrenergic responsiveness (108 +/- 3 microns/s). LV myocardial ACE activity increased in REC compared to control (5.82 +/- 0.21 v 3.51 +/- 0.15 nmol/mg/min, P < 0.05). With ACEI--14 or ACEI--28, myocardial ACE activity was decreased compared to REC (4.16 +/- 0.06 and 4.08 +/- 0.23 nmol/mg/min; P < 0.05). In control dogs administered ACEI, there were no differences in any of these parameters compared to controls. The unique findings in this study were: (1) effects of ACEI treatment in this model of LV hypertrophy were time dependent with respect to LV mass and LV and myocyte function; and (2) the effect of ACEI treatment on the degree of LV hypertrophy appears to not be solely due modulation of myocardial ACE activity.

Angiotensin-converting enzyme inhibition and angiotensin II subtype-1 receptor blockade during the progression of left ventricular dysfunction: differential effects on myocyte contractile processes.

Inhibition of the angiotensin-converting enzyme (ACE) in the setting of chronic left ventricular (LV) dysfunction has been demonstrated to have beneficial effects on survival and symptoms. However, whether ACE inhibition has direct effects on myocyte contractile processes and if these effects are mediated primarily through the AT1 angiotensin-II receptor subtype remains unclear. The present project examined the relationship between changes in LV and myocyte function and beta adrenergic receptor transduction in four groups of six dogs each: (1) Rapid Pace: LV failure induced by chronic rapid pacing (4 weeks; 216 +/- 2 bpm); (2) Rapid Pace/ACEI: concomitant ACE inhibition (ACEI: fosinopril 30 mg/kg b.i.d.) with chronic pacing; (3) Rapid Pace/AT1 Block: concomitant AT1 Ang-II receptor blockade [Irbesartan: SR 47436(BMS-186295) 30 mg/kg b.i.d.] with chronic pacing; and (4) CONTROL: sham controls. With Rapid Pace, the LV end-diastolic volume increased by 62% and the ejection fraction decreased by 53% from control. With Rapid Pace/ACEI, the LV end-diastolic volume was reduced by 24% and the ejection fraction increased by 26% from Rapid Pace only values. Rapid Pace/AT1 Block did not improve LV geometry or function from Rapid Pace values. Myocyte contractile function decreased by 40% with Rapid Pace and increased from this value by 32% with Rapid Pace/ACEI. Rapid Pace/AT1 Block had no effect on myocyte function when compared with Rapid Pace values. With Rapid Pace/ACEI, beta receptor density and cyclic AMP production were normalized and associated with an improvement in myocyte beta adrenergic response compared with Rapid Pace only. Although Rapid Pace/AT1 also normalized beta receptor density, cyclic AMP production was unchanged and myocyte beta adrenergic response was reduced by 15% compared with Rapid Pace only. ACE inhibition with chronic rapid pacing improved LV and myocyte geometry and function, and normalized beta receptor density and cyclic AMP production. However, AT1 Ang-II receptor blockade with chronic rapid pacing failed to provide similar protective effects on LV and myocyte geometry and function. These unique findings suggest that the effects of ACE inhibition on LV geometry and myocyte contractile processes in the setting of developing LV failure are not primarily caused by modulation of AT1 Ang-II receptor activation.