Peroxynitrite Footprint in Circulating Neutrophils of Abdominal Aortic Aneurysm Patients is Lower in Statin than in Non-statin Users.

OBJECTIVES: Extensive reactive oxygen and nitrogen species (also reactive species) production is a mechanism involved in abdominal aortic aneurysm (AAA) development. White blood cells (WBCs) are a known source of reactive species. Their production may be decreased by statins, thereby reducing the AAA growth rate. Reactive species production in circulating WBCs of AAA patients and the effect of statins on their production was investigated. METHODS: This observational study investigated reactive species production in vivo and ex vivo in circulating WBCs of AAA patients, using venous blood from patients prior to elective AAA repair (n = 34; 18 statin users) and from healthy volunteers (n = 10). Reactive species production was quantified in circulating WBCs using immunofluorescence microscopy: nitrotyrosine (footprint of peroxynitrite, a potent reactive nitrogen species) in snap frozen blood smears; mitochondrial superoxide and cytoplasmic hydrogen peroxide (both reactive oxygen species) by live cell imaging. Neutrophils, lymphocytes, and monocytes were examined individually. RESULTS: In AAA patients using statins, the median nitrotyrosine level in neutrophils was 646 (range 422-2059), in lymphocytes 125 (range 74-343), and in monocytes 586 (range 291-663). Median levels in AAA patients not using statins were for neutrophils 928 (range 552-2095, p = .03), lymphocytes 156 (101-273, NS), and for monocytes 536 (range 535-1635, NS). The statin dose tended to correlate negatively with nitrotyrosine in neutrophils (Rs -0.32, p = .06). The median levels in controls were lower for neutrophils 466 (range 340-820, p < .01) and for monocytes 191 (range 102-386, p = .03), but similar for lymphocytes 99 (range 82-246) when compared to the AAA patients. There were no differences in mitochondrial superoxide and cytoplasmic hydrogen peroxide between statin and non-statin users within AAA patients. CONCLUSIONS: It was found that the peroxynitrite footprint in circulating neutrophils and monocytes of AAA patients is higher than in controls. AAA patients treated with statins had a lower peroxynitrite footprint in neutrophils than non-statin users.

Alteration by p11 of mGluR5 localization regulates depression-like behaviors.

Mood disorders and antidepressant therapy involve alterations of monoaminergic and glutamatergic transmission. The protein S100A10 (p11) was identified as a regulator of serotonin receptors, and it has been implicated in the etiology of depression and in mediating the antidepressant actions of selective serotonin reuptake inhibitors. Here we report that p11 can also regulate depression-like behaviors via regulation of a glutamatergic receptor in mice. p11 directly binds to the cytoplasmic tail of metabotropic glutamate receptor 5 (mGluR5). p11 and mGluR5 mutually facilitate their accumulation at the plasma membrane, and p11 increases cell surface availability of the receptor. Whereas p11 overexpression potentiates mGluR5 agonist-induced calcium responses, overexpression of mGluR5 mutant, which does not interact with p11, diminishes the calcium responses in cultured cells. Knockout of mGluR5 or p11 specifically in glutamatergic neurons in mice causes depression-like behaviors. Conversely, knockout of mGluR5 or p11 in GABAergic neurons causes antidepressant-like behaviors. Inhibition of mGluR5 with an antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), induces antidepressant-like behaviors in a p11-dependent manner. Notably, the antidepressant-like action of MPEP is mediated by parvalbumin-positive GABAergic interneurons, resulting in a decrease of inhibitory neuronal firing with a resultant increase of excitatory neuronal firing. These results identify a molecular and cellular basis by which mGluR5 antagonism achieves its antidepressant-like activity.

Health economic analysis of total extraperitoneal repair versus Lichtenstein surgery for inguinal hernia: data from a randomized clinical trial.

BACKGROUND: The aim was to compare cost-effectiveness of Lichtenstein under local anaesthesia (LLA) with total extraperitoneal repair (TEP) under general anaesthesia for primary inguinal hernia in men. An endoscopic approach to inguinal hernia repair is often considered costlier. The cost of endoscopic hernia repair, however, has not been compared to open inguinal hernia repair in a cost-effective setting. METHODS: Data from an RCT comparing TEP and Lichtenstein in a cost-effective setting, with health economy as a secondary endpoint, were used. Data on costs were collected prospectively. Data on sick leave were obtained from the Swedish Social Insurance Agency in order to compare lengths of sick leave. RESULTS: In total, 384 patients were included and 374 (97.4 per cent) patients were available for analysis, 189 in the LLA group and 185 in the TEP group. The median operating time for LLA was 70 (i.q.r. 60-80) min compared with 60 (i.q.r. 50-75) min in the TEP group (P < 0.001). The median time in operating theatre was 114 (i.q.r. 95--125) min for LLA and 125 (i.q.r. 110-145) min for TEP (P < 0.001). The median cost including all materials was 2433 (i.q.r. 2084-2734) Euros for LLA and 2395 (i.q.r. 2093-2784) Euro for TEP (P = 0.650). Mean sick leave was 4.2 days in the LLA group and 6.2 days in the TEP group (P = 0.830). CONCLUSION: The overall cost to the hospital or length of sick leave did not differ between LLA and TEP.

Anchored multiplex amplification on a microelectronic chip array.

We have developed a method for anchored amplification on a microchip array that allows amplification and detection of multiple targets in an open format. Electronic anchoring of sets of amplification primers in distinct areas on the microchip permitted primer-primer interactions to be reduced and distinct zones of amplification created, thereby increasing the efficiency of the multiplex amplification reactions. We found strand displacement amplification (SDA) to be ideal for use in our microelectronic chip system because of the isothermal nature of the assay, which provides a rapid amplification system readily compatible with simple instrumentation. Anchored SDA supported multiplex DNA or RNA amplification without decreases in amplification efficiency. This microelectronic chip-based amplification system allows multiplexed amplification and detection to be performed on the same platform, streamlining development of any nucleic acid-based assay.

Self assembly, structure and properties of the decanuclear lanthanide ring complex, Dy10(OC2H4OCH3)30.

Self assembly produced high yields of the lanthanide ring complex Dy10(OC2H4OCH3)30, the largest lanthanide ring known, characterized by X-ray diffraction methods and by magnetic susceptibility as a function of temperature.

Influence of coronary nursing management follow up on lifestyle after acute myocardial infarction.

OBJECTIVE: To examine the ability of a secondary prevention programme to improve the lifestyle in myocardial infarction patients aged 50-70 years. DESIGN: Habitual physical activity, food habits, and smoking habits were assessed from questionnaires at admission to hospital and at the one year follow up. Initially, all patients were invited to join an exercise programme and were informed about cardiovascular risk factors. Four weeks after discharge from the hospital, 87 patients were randomised to follow up at the coronary prevention unit by a special trained nurse (the intervention group), and 81 to follow up by their general practitioners (the usual care group). After randomisation, the intervention group was educated about the effects of smoking cessation, dietary management, and regular physical activity. The intervention group also participated in a physical training programme two to three times weekly for 10-12 weeks. MAIN RESULTS: 89% of the patients referred to the intervention group improved their food habits compared with 62% of the patients referred to the usual care group (P = 0.008). Furthermore, 50% of the smokers referred to the intervention group stopped smoking compared to 29% in the usual care group (P = 0.09). Changes in physical activity did not differ between the groups. CONCLUSIONS: This secondary prevention programme based on a nurse rehabilitator was successful in improving food habits in patients with acute myocardial infarction. Initiating the smoking cessation programme during the hospital stay followed by repeated counselling during follow up might have improved the results. The exercise programme had no advantage in supporting physical activity compared to usual care.

Study of protein and RNA in dendritic spines using multi-isotope imaging mass spectrometry (MIMS).

The classical view of neuronal protein synthesis is that proteins are made in the cell body and then transported to their functional sites in the dendrites and the dendritic spines. Indirect evidence, however, suggests that protein synthesis can directly occur in the distal dendrites, far from the cell body. We are developing protocols for dual labeling of RNA and proteins using 15N-uridine and 18O- or 13C-leucine pulse chase in cultured neurons to identify and localize both protein synthesis and fate of newly synthesized proteins. Pilot experiments show discrete localization of both RNA and newly synthesized proteins in dendrites, close to dendritic spines. We have for the first time directly imaged and measured the production of proteins at the subcellular level in the neuronal dendrites, close to the functional sites, the dendritic spines. This will open a powerful way to study neural growth and synapse plasticity in health and disease.

Validity of the classical monte carlo method to model the magnetic properties of a large transition-metal cluster: Mn19.

The susceptibility of the large transition-metal cluster [Mn19O12(MOE)14(MOEH)10].MOEH (MOE = OC2H2O-CH3) has been fitted through classical Monte Carlo simulation, and an estimation of the exchange coupling constants has been done. With these results, it has been possible to perform a full-matrix diagonalization of the cluster core, which was used to provide information on the nature of the low-lying levels.

Patients with ischemic heart disease: quality of life predicts long-term mortality.

OBJECTIVE: We have investigated whether perceived quality of life has an impact on long-term survival after a cardiac event. DESIGN: Male (n = 316) and female (n = 97) patients were assessed by means of a self-administered quality of life questionnaire 1 year after either acute myocardial infarction (n = 296), coronary artery bypass grafting surgery (n = 99) or percutaneous coronary intervention (n = 18). Inclusion period was 1989-1991. Ten years after the last patient answered the 1-year questionnaire, mortality (status factor) up to census date was analysed using nine dimensions of quality of life as covariates (Cox regression). RESULTS: At 1-year assessment, subjective general health (RR = 3.15), perceived arrhythmia (RR = 1.72), experience of sex life (RR = 1.55), perceived breathlessness (RR = 1.50) and experience of self-esteem (RR = 1.48) were all significantly related to death within the period up to census date. CONCLUSION: The findings highlight that the patients' own experience of his or her quality of life, has a prognostic importance for long-term mortality after a cardiac event. Clinicians should be aware that a careful monitoring of perceived quality of life is an important part of good patient care.

Oesophagus scintigraphy in patients with diabetes mellitus.

Oesophagus scintigraphy with 99mTc was used to evaluate oesophageal motility in 40 patients with insulin-dependent diabetes mellitus. Abnormal oesophageal function was found in one third of the patients, although none reported oesophageal symptoms. The patients with abnormal oesophageal motility had a high frequency of abnormal autonomic nerve function tests compared with controls.

Preparation, structure, and properties of a new giant manganese oxo-alkoxide wheel, [Mn19O12(OC2H4OCH3)14(HOC2H4OCH3)10]. HOC2H4OCH3.

Alkoxides are of great interest as precursors for sol-gel processing of advanced ceramic materials, but there is very little general knowledge about the low-valent 3d-element alkoxides. The novel oxo-alkoxide, [Mn19O12(moe)14-(moeH)10].MOEH (MOE = OC2H2-OCH3), was prepared, by metathesis and auto-decomposition, from MnCl2 and potassium methoxyethoxide in toluene/MOEH, and the solid-state structure was determined from single-crystal X-ray diffraction data: trigonal cell, space group R3 (no. 148), a = 27.560(3), c = 19.294(2) A, Z = 3, R1 = 0.0737, wR2 = 0.1609. The individual molecules are shaped as flat discs and all Mn atoms are divalent and octahedrally coordinated by oxygen atoms in a CdI2-type layer structure. The central Mn atom is coordinated by six mu3-oxo atoms, the six middle ring Mn-atoms by two mu3-oxo atoms and four MOE(H) groups, while the peripheral ring contains twelve Mn atoms coordinated by one mu3-oxo atom and five MOE(H) groups. Differential scanning calorimetry studies showed that the first and irreversible changes start at about 100 degrees C. The continuous decrease of (chiM)T with decreasing temperature below 150 K in the magnetic susceptibility measurements is probably due to antiferromagnetic interactions. FTIR and UV/Vis spectroscopy of solid and dissolved samples showed that the solid-state structure changes at least to some extent on dissolution in toluene/MOEH.

Serum lipids four weeks after acute myocardial infarction are a valid basis for lipid lowering intervention in patients receiving thrombolysis.

OBJECTIVE: To compare serum concentrations of total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and triglycerides four weeks after acute myocardial infarction with baseline levels measured within 24 hours after onset of symptoms. DESIGN: A prospective study including 141 patients with acute myocardial infarction who were admitted to the coronary care unit at a general hospital. MEASUREMENTS: Fasting serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. MAIN RESULTS: In patients receiving thrombolytic therapy, no significant differences were found in serum lipids four weeks after admission compared to values estimated within 24 hours from onset of symptoms. In patients not receiving thrombolytic therapy, total cholesterol and low density lipoprotein cholesterol showed a minor increase four weeks after admission compared to values obtained within 24 hours after onset of symptoms. High density lipoprotein cholesterol and triglycerides remained unchanged. CONCLUSIONS: In patients with acute myocardial infarction receiving thrombolytic therapy, serum lipids measured four weeks after onset of infarction are reasonably valid estimates of baseline lipid levels and may be used to decide about lipid lowering interventions. This information can be a basis for actions against hyperlipidaemia early after hospital discharge when the patient is highly motivated to change lifestyles and is still in close contact with a cardiologist or other physician.

Triple helix DNA alters nucleosomal histone-DNA interactions and acts as a nucleosome barrier.

Oligonucleotides which form triple helical complexes on double-stranded DNA have been previously reported to selectively inhibit transcription both in vitro and in vivo by physically blocking RNA polymerase or transcription factor access to the DNA template. Here we show that a 16mer oligonucleotide, which forms triple helix DNA by binding to a 16 bp homopurine segment, alters the formation of histone-DNA contacts during in vitro nucleosome reconstitution. This effect was DNA sequence-specific and required the oligonucleotide to be present during in vitro nucleosome reconstitution. Binding of the triple helix oligonucleotide on a 199 bp mouse mammary tumour virus promoter DNA fragment with a centrally located triplex DNA resulted in interruption of histone-DNA contacts flanking the triplex DNA segment. When nucleosome reconstitution is carried out on a longer, 279 bp DNA fragment with an asymmetrically located triplex site, nucleosome formation occurred at the border of the triple helical DNA. In this case the triplex DNA functioned as a nucleosome barrier. We conclude that triplex DNA cannot be accommodated within a nucleosome context and thus may be used to site-specifically manipulate nucleosome organization.

Long-term effects on cholesterol levels and the utilization of lipid-lowering drugs of a hospital-based programme for secondary prevention of coronary artery disease.

BACKGROUND: The study was designed to determine whether a 1-year hospital-based secondary prevention programme would have any long-term effects on serum lipid levels and the use of lipid-lowering drugs in patients with coronary artery disease 4 years after referral to primary care facilities for follow-up. DESIGN/METHODS: After acute myocardial infarction or coronary bypass surgery, 241 consecutive patients were randomly assigned to conventional care (CC) by the primary health care facilities or to a 1-year hospital-based secondary prevention programme (SPP) with target levels for serum cholesterol (< 5.2 mmol/l) and triglycerides (< 1.5 mmol/l). After 1 year all patients were referred to the primary care sector for a further 4-year follow-up. RESULTS: At the 1-year follow-up there was a significant decrease in serum cholesterol, LDL-cholesterol and triglyceride levels in the SPP group but no change in the CC group, and lipid-lowering drugs were used more frequently in the SPP group. These changes were maintained after 5 years. The proportion of patients achieving target serum cholesterol and triglyceride levels were larger in the SPP group. CONCLUSIONS: Initiatives regarding cholesterol lowering and drug treatment taken by specialists within a structured hospital-based SPP have long-term impact. Accordingly, drug treatment should be initiated and adjusted to adequate doses before patients are referred to primary care for follow-up.

[Need for a long-term program in the follow-up of anti-lipid treatment following coronary artery surgery?]. / Behövs långsiktiga program för uppföljning av blodfettsbehandling efter kranskärlskirurgi?

The positive effects of cholesterol-lowering therapy in coronary artery disease are well recognised. This study, on 99 consecutive coronary artery bypass grafted patients, shows that an intensive one-year follow-up at a secondary prevention specialist clinic significantly improves cholesterol levels compared to conventional follow-up in the primary health care system. However, these positive results are not consistent after a 2.6 year return to the primary health care. Consequently, improved collaboration between hospital and primary health care physicians in the development of structured secondary prevention programmes is essential.

Quality of life in patients with ischaemic heart disease: a prospective controlled study.

OBJECTIVES: To assess quality of life in patients after acute myocardial infarction (AMI), coronary artery by-pass grafting surgery (CABG) and percutaneous transluminal coronary angioplasty (PTCA) as compared with healthy controls. DESIGN: Self-administered questionnaires were completed 1 month and 1 year after the event. SETTING: Department of Cardiology, University Hospital, Malmö, Sweden; 1989-1992. SUBJECTS: 296 AMI, 99 CABG, 18 PTCA patients and 88 randomly selected healthy controls were included; 349 patients completed the entire programme. MAIN OUTCOME MEASURES: Quality of life in the dimensions of perceived general health, thoracic pain, breathlessness, feeling of arrhythmia, anxiety, depression, self-esteem, experience of social life and sex life. RESULTS: Patients differed from controls in both psychological and somatic aspects of QL after 1 month. Furthermore, 1 month after the event AMI patients experienced more anxiety (P = 0.001) than CABG patients, whilst CABG patients experienced a poorer sex life (P < 0.001) than AMI patients. One year after the event patients differed from controls primarily in somatic symptoms: no significant differences were found across patient groups. Patients who sought emergency out-patient care during the follow-up year for clinically diagnosed angina pectoris or cardiac incompensation had reported higher levels of thoracic pain (P < 0.001) and breathlessness (P < 0.001) at 1 month follow-up than patients who did not seek such care. CONCLUSIONS: Quality of life is considerably affected in patients following a cardiac event, especially during the initial recovery phase. Although substantial improvement in quality of life occurs over time, the persistence of residual distress at 1-year follow-up is a challenge for clinicians concerned with the full rehabilitation of the cardiac patient.

Differences in quality of life in men and women with ischemic heart disease. A prospective controlled study.

A study was conducted in Sweden in 1989-1992 to evaluate differences in quality of life (QL) in consecutive male and female patients after acute myocardial infarction (AMI), coronary artery by-pass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). Somatic and psychological dimensions of QL were assessed by self-administered questionnaire in patients one month (n = 376) and one year (n = 349) after the cardiac event. Normal controls (n = 88) were used for comparison. Differences between gender groups, as well as between study patients and controls in somatic and psychological dimensions of QL were studied. Patients were shown to experience poorer QL when compared with demographically similar controls, especially at the one-month assessment. Female patients had poorer QL after one month (in general health, feeling of arrythmia, anxiety, depression, self-esteem, experience of sex life) and after one year (general health, anxiety, depression) compared with male patients. In all dimensions of QL a proportion of patients (19-45%) experienced a decrease in QL from the one-month to the one-year assessment occasion. Healthcare workers concerned with secondary prevention must be aware that QL differs between male and female patients in several dimensions after a cardiac event. These findings should be taken into account in the clinical management of patients, particularly for female patients who may need special attention.