Syntheses and catalytic oxotransfer activities of oxo molybdenum(vi) complexes of a new aminoalcohol phenolate ligand.

The new aminoalcohol phenol 2,4-di-tert-butyl-6-(((2-hydroxy-2-phenylethyl)amino)methyl)phenol (H2L) was prepared by a facile solvent-free synthesis and used as a tridentate ligand for new cis-dioxomolybdenum(vi)(L) complexes. In the presence of a coordinating solvent (DMSO, MeOH, pyridine), the complexes crystallise as monomeric solvent adducts while in the absence of such molecules, a trimer with asymmetric Mo[double bond, length as m-dash]O→Mo bridges crystallises. The complexes can catalyse epoxidation of cis-cyclooctene and sulfoxidation of methyl-p-tolylsulfide, using tert-butyl hydroperoxide as oxidant.

Decline in out-of-hospital coronary heart disease deaths has contributed the main part to the overall decline in coronary heart disease mortality rates among persons 35 to 64 years of age in Finland: the FINAMI study.

BACKGROUND: Out-of-hospital deaths constitute the majority of all coronary heart disease (CHD) deaths and are therefore of considerable public health significance. METHODS AND RESULTS: We used population-based myocardial infarction register data to examine trends in out-of-hospital CHD deaths in Finland during 1983 to 1997. We included in out-of-hospital deaths also deaths in the emergency room and all deaths within 1 hour after the onset of symptoms. Altogether, 3494 such events were included in the analyses. The proportion of out-of-hospital deaths of all CHD deaths depended on age and gender. In the age group 35 to 64 years, it was 73% among men and 60% among women. These proportions did not change during the study. The annual average decline in the age-standardized out-of-hospital CHD death rate was 6.1% (95% CI, -7.3, -5.0%) among men and 7.0% (-10.0, -4.0%) among women. These declines contributed among men 70% and among women 58% to the overall decline in CHD mortality rate. In all, 58% of the male and 52% of the female victims of out-of-hospital CHD death had a history of symptomatic CHD. Among men with a prior history of myocardial infarction, the annual average decline in out-of-hospital CHD deaths was 5.3% (-7.2, -3.2%), and among men without such history the decline was 2.9% (-4.4, -1.5%). Among women, the corresponding changes were -7.8% (-14.2, -1.5%) and -4.5% (-8.0, -1.0%). CONCLUSIONS: The decline in out-of-hospital CHD deaths has contributed the main part to the overall decline in CHD mortality rates among persons 35 to 64 years of age in Finland.

Thymoma with immunodeficiency (Good's syndrome) associated with myasthenia gravis and benign IgG gammopathy.

We treated a case of thymoma with immunodeficiency (Good's syndrome) associated with a rare combination of other parathymic syndromes including myasthenia gravis, benign IgG lambda M component, pernicious anemia, and diabetes. The characterization of the patient's immunologic capacity disclosed practically normal T-cell number and mitogenic responses but impaired lymphokine production as well as B-cell function.

Aminobisphenolate supported tungsten disulphido and dithiolene complexes.

Dioxotungsten(vi) complexes with tetradentate amino bisphenolates were converted into the corresponding Cs-symmetric amino bisphenolate disulphido complexes by a reaction with either Lawesson's reagent or P2S5. Further reaction with diethyl acetylenedicarboxylate leads to the formation of diamagnetic tungsten(iv) dithiolene compounds. The syntheses, crystal structures, spectroscopic and electrochemical characterization of such disulphido and dithiolene complexes are presented.

Inverse correlation between serum testosterone and leptin in men.

Besides its role in the regulation of energy balance, leptin seems to be involved in linking energy stores to the reproductive system. A gender-dependent difference exists in plasma leptin concentration and leptin messenger ribonucleic acid expression in rodents and humans. This difference does not seem to be explained simply by differences in the amount of body fat between genders. To elucidate the relationship of endogenous testosterone and leptin, we studied the serum leptin concentrations in 269 elderly nondiabetic men. In addition, to assess whether exogenously administered testosterone could influence leptin production, we followed the serum levels of leptin in 10 healthy men during a 12-month treatment with 200 mg testosterone enanthate, i.m., weekly for contraceptive purposes. We found that the serum leptin concentration correlated inversely (r = -0.39; P < 0.001) with that of testosterone in elderly men. This inverse correlation was still present when body mass index and plasma insulin were included in the analysis. The administration of testosterone to young men suppressed serum leptin from the pretreatment level of 3.4 +/- 1.4 to 1.9 +/- 0.6 micrograms/L during the therapy. After cessation of testosterone injections, serum leptin concentration returned back to the pretreatment level. It is concluded that testosterone has a suppressive effect on leptin production, as reflected by circulating levels of this hormone.

Unusual association of hyperkalemia and hypertension.

We report an unusual association of hyperkalemia, mild hyperchloremic acidosis, and hypertension in a young woman. Pseudohyperkalemia, Addison's disease, renal insufficiency, classical hyporeninemic hypoaldosteronism, isolated hypoaldosteronism, and iatrogenic causes were excluded. The patient's findings were compatible with a rare syndrome designated as type II pseudohypoaldosteronism, Gordon's syndrome.

Ambulatory monitoring uncorrected for placebo overestimates long-term antihypertensive action. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.

This study compares blood pressure (BP) changes during active antihypertensive treatment and placebo as assessed by conventional and ambulatory BP measurement. Older patients (> or = 60 years, n=337) with isolated systolic hypertension by conventional sphygmomanometry at the clinic were randomized to placebo or active treatment consisting of nitrendipine (10 to 40 mg/d), with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d). At baseline, clinic systolic/diastolic BP averaged 175/86 mm Hg and 24-hour and daytime ambulatory BPs averaged 148/80 and 154/85 mm Hg, respectively. After 13 months (median) of active treatment, clinic BP had dropped by 22.7/7.0 mm Hg and 24-hour and daytime BPs by 10.5/4.5 and 9.7/4.3 mm Hg, respectively (P<.001 for all). However, clinic (9.8/1.6 mm Hg), 24-hour (2.1/1.1 mm Hg), and daytime (2.9/1.0 mm Hg) BPs decreased also during placebo (P<.05, except for daytime diastolic BP); these decreases represented 43%/23%, 20%/24%, and 30%/23% of the corresponding BP fall during active treatment. After subtraction of placebo effects, the net BP reductions during active treatment averaged only 12.9/5.4, 8.3/3.4, and 6.8/3.2 mm Hg for clinic, 24-hour, and daytime BPs, respectively. The effect of active treatment was also subject to diurnal variation (P<.05). Changes during placebo in hourly systolic and diastolic BP means amounted to (median) 21% (range, -1% to 42%) and 25% (-3% to 72%), respectively, of the corresponding changes during active treatment. In conclusion, expressed in millimeters of mercury, the effect of antihypertensive treatment on BP is larger with conventional than with ambulatory measurement. Regardless of whether BP is measured by conventional sphygmomanometry or ambulatory monitoring, a substantial proportion of the long-term BP changes observed during active treatment may be attributed to placebo effects. Thus, ambulatory monitoring uncorrected for placebo or control observations, like conventional sphygmomanometry, overestimates BP responses in clinical trials of long duration.

The proximal interferon-stimulated response elements are essential for interferon responsiveness: a promoter analysis of the antiviral MxA gene.

Interferon (IFN)-inducible human MxA protein mediates resistance against influenza and several other RNA viruses. The MxA gene is under the control of type I IFN and, in certain cell types, is also directly activated by viruses. Here we show that in human macrophages, MxA mRNA levels are upregulated by very low doses of IFN-alpha in a dose-dependent manner. A similar, albeit much weaker, dose-dependent induction was seen with IFN-gamma. The induction was rapid and independent of protein synthesis. Interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) did not influence MxA mRNA levels alone or in combination with IFNs, in spite of the presence of putative response elements of these cytokines in the MxA promoter. We show that the promoter of the MxA gene contains two functional IFN-stimulated response elements (ISRE) near the transcription start site and one homologous ISRE-like element, which is apparently nonfunctional, further upstream. The two proximal ISRE sites are essential for IFN-alpha-induced transcription and appear to be binding sites for IFN-stimulated gene factor 3 complex. In addition, EMSA and DNAse I footprinting analysis demonstrated that Spl binds with high affinity to a region encompassing nucleotides -25 and -50 and, thus, may provide means of interaction with the basal transcriptional machinery.

Effect of high dose progestin on serum lipids.

The effect of high dose medroxyprogesterone (MPA) on serum lipids was studied in 31 postmenopausal patients with endometrial cancer. After 3 months of MPA treatment, total cholesterol decreased by 18% (P less than 0.001), LDL cholesterol by 16% (P less than 0.01) and HDL cholesterol by 38% (P less than 0.001) from the respective pretreatment values; correspondingly, the ratio of HDL to total cholesterol decreased (P less than 0.001). Similar changes were found as early as 2 weeks after start of treatment. In the 15 controls receiving no progestin treatment, full dose intracavitary radiotherapy and gynecological surgery had no effect on these serum lipids.

Long-term effect of the combination of calcium clofibrate and calcium carbonate on serum total cholesterol, triglyceride and high density lipoprotein--cholesterol concentrations in hyperlipoproteinaemia. A comparative study with clofibrate.

Thirty hyperlipidaemic patients (19 with type IIA, 4 with IIB and 7 with type IV hyperlipoproteinaemia) were subjected to therapy with calcium clofibrate and calcium carbonate (4C, 2 + 2 g/day for 6 months) and the effect was compared with clofibrate (1C, 2 g/day) which was given for 6 months as well, in a single-blind placebo-controlled study. 4C and 1C decreased total serum cholesterol levels especially in subgroups IIA and IIB. 4C was somewhat more effective than 1C in decreasing (VLDL + LDL)-cholesterol in subgroup IIA. The HDL-cholesterol concentrations and the ratio of HDL-cholesterol and total cholesterol increased during treatment with both 1C and 4C. The HDL-cholesterol increase (vs. placebo) was 18%. The concentrations of serum triglycerides decreased by 33% during both treatment periods and there was no significant difference between 1C and 4C.

Effect of atenolol on plasma HDL cholesterol subfractions.

The effect of atenolol on plasma HDL cholesterol subfractions and other plasma lipids in 18 patients with essential hypertension was studied. The atenolol was given orally, in a dose of 100 mg once daily for 6 months. The level of HDL cholesterol during atenolol treatment was significantly lower than before it. The concentration of HDL2 cholesterol decreased (P less than 0.01) during the first month of therapy and remained constant during treatment. The level of HDL3 cholesterol decreased slightly but not significantly. The concentrations of plasma triglycerides and total cholesterol increased slightly during atenolol treatment; statistical significance was reached (P less than 0.05) at 6 months.

Serum from type IIA hyperlipoproteinemic patients does not stimulate proliferation of and collagen synthesis in human fetal aortic smooth muscle cells in culture.

The effect of serum from type IIA hyperlipoproteinemic patients on the proliferation and synthesis of collagen and other proteins of human fetal aortic smooth muscle cells (SMC) was studied. The activity of lysyl oxidase secreted into the culture medium was also measured. Type IIA hyperlipoproteinemic sera did not affect the proliferation of human aortic SMC as compared to normolipidemic sera, regardless of incubation time. The findings were similar for 3 different human fetal aortic SMC lines and one fibroblast line from adult human skin. The synthesis of collagen and other proteins was inhibited rather than stimulated in the presence of type IIA hyperlipoproteinemic sera. The activity of lysyl oxidase was not affected by type IIA hyperlipoproteinemic sera. The atherogenicity of hypercholesterolemia cannot be explained either by its direct effect on the proliferation of arterial SMC, as has been suggested by animal cell studies, or by its direct effect on the fibrogenicity of these cells.

High density lipoproteinemia due to vigorous physical work inhibits the incorporation of [3H]thymidine and the synthesis of glycosaminoglycans by human aortic smooth muscle cells in culture.

The effect of sera from normolipidemic men engaging in normal physical activity and from high density lipoproteinemic lumberjacks engaging in vigorous physical activity on the incorporation of [3H]thymidine and the synthesis of glycosaminoglycans by human aortic smooth muscle cells in culture was measured. At high concentration (15%) high density lipoproteinemic serum inhibited significantly (P less than 0.001) the incorporation of thymidine. The serum inhibited the synthesis of glycosaminoglycans at all concentrations tested (1--15%) with the most marked inhibition at 10 and 15%. At lower concentrations (1--5%) the inhibition was more pronounced for sulphated glycosaminoglycans than for hyaluronic acid. The inhibition was of the same magnitude for the subclasses (chondroitin, dermatan and heparan sulphates) of sulphated glycosaminoglycans studied. High density lipoproteinemia due to vigorous physical work is postulated as a protective factor against the early biochemical reactions of arterial smooth muscle cells in the development of atherosclerosis.

Connective tissue components in normal and atherosclerotic human coronary arteries.

Human coronary arteries with various degrees of atherosclerosis were analyzed for the concentration of different types of glycosaminoglycans (GAGs). The changes in GAGs were considered against the background of macroscopic atherosclerosis, and the concentration of glycoprotein-bound hexosamines, collagen, calcium and cholesterol. The concentration of calcium was increased and that of hyaluronic acid decreased even in mildly atherosclerotic coronary arteries. The additional changes in advanced atherosclerosis included the increase of collagen and dermatan sulphate and the decrease of heparan sulphate. Cholesterol was increased in mild, and even further in advanced, atheroslcerosis. The concentrations of chondroitin sulphates and glycoprotein-bound hexosamines were not significantly affected by atherosclerosis.

Growth of human aortic smooth muscle cells cultured with human serum is retarded when serum lipids are lowered by medroxyprogesterone.

Human aortic smooth muscle cells were cultured in the presence of sera from 7 normolipidemic women before and after treatment with high-dose medroxyprogesterone acetate, which caused 16% and 25% decreases in serum cholesterol and HDL-cholesterol concentrations, respectively. As assessed by cell counting and by DNA determination the growth of the cells was retarded significantly in the presence of sera taken after the treatment. At the same time, there were no marked changes in the incorporation rate of [3H]proline into collagen or [3H]glucosamine into hyaluronic acid by the cells. The results indicate that: (1) the mitogenicity of human serum can be altered by drug treatment of serum donors, (2) simultaneously with a lowering of serum lipids in man in vivo, a decreased mitogenicity of sera occurs in vitro.

Type IIA hyperlipoproteinemic sera decrease the synthesis of hyaluronic acid by cultured human aortic smooth muscle cells.

The synthesis of sulphated glucosaminoglycans (S-GAGs) and hyaluronic acid (HA) by cultured human aortic smooth muscle cells (SMC) was measured in the presence of sera from type IIA hyperlipoproteinemic patients (7 males and 6 females) and their age- and sex-matched controls. Experiments with pooled sera showed that type IIA and control sera differed in their effects on the synthesis of GAGs at high serum concentrations with preincubation times of 24 and 48 h. Therefore, individual sera were tested at 15% with 24 h preincubation. Type IIA sera decreased the synthesis of HA by 21% (P less than 0.001) but had no significant effect on sulphated GAGs. The ratio of sulphated GAGs to Ha was higher in the presence of type IIA sera than control sera. The incorporation of thymidine, the number of cells and the amount of DNA did not differ in cultures incubated with type IIA and control sera. Early human and experimental atherosclerotic lesions are known to have an increased sulphated GAGs to HA ratio. Our results suggest that one explantation for the association between type IIA hyperlipoproteinemia and an increased risk for atherosclerosis is the disturbance in the proportions of hyaluronic acid and sulphated GAGs synthesized by arterial SMC.

Levels of serum lipids, apolipoproteins A-I and B and pseudocholinesterase activity and their discriminative values in patients with coronary by-pass operation.

Serum lipids and apoproteins A-I and B were measured in 115 male patients and serum pseudocholinesterase activity (PChE) was determined in 83 patients with 3 vessel coronary artery disease (CAD). The control subjects were matched according to sex, smoking, relative weight and age and were free from heart disease. The CAD patients had significantly higher serum VLDL cholesterol and triglyceride levels and lower HDL cholesterol and apo A-I levels and lower HDL to total cholesterol ratio than the controls. The concentrations of serum total cholesterol and LDL cholesterol were only slightly (6.4% and 8.8%, on an average) higher in CAD patients than in controls. The apo B levels of CAD patients were also slightly lower in patients than in controls. The CAD patients had slightly higher PChE activities than controls. The ratios of apo A-I to PChE and HDL cholesterol to PChE were significantly (about 30%, P less than 0.001) lower in patients than in controls. In discriminant analysis between the groups HDL cholesterol and apo A-I showed the best (74% success in reclassifying the patients to correct groups), and total cholesterol, triglycerides, LDL cholesterol and apo B remarkably weak discriminating power among the single variables of serum lipids and lipoproteins. In discriminating analysis the apo A-I/PChE and HDL cholesterol/PChE ratios showed relatively high (77.1 and 71.1% success from the patients to correct groups) and serum PChE activity weak discriminating power. These results indicate that low levels of HDL cholesterol and apo A-I and the low ratio of HDL cholesterol to total cholesterol are the most potent metabolic risk factors for 3 vessel coronary artery disease in a population with relatively high serum total cholesterol level. The determinations of apo A-I/PChE and HDL cholesterol/PChE ratios may be an additional, valuable tool in discriminating the risk for CAD.

Ambulatory pressure decreases on long-term placebo treatment in older patients with isolated systolic hypertension. Syst-Eur Investigators.

OBJECTIVE: This long-term study investigated the widely accepted hypothesis that ambulatory pressure does not decrease in patients given placebo. METHODS: One hundred and twelve older (> or = 60 years) outpatients with isolated systolic hypertension were recruited. Treatment consisted of a placebo during a 3-month baseline period and long-term follow-up. RESULTS: At baseline, on placebo treatment, clinic systolic/diastolic (SBP/DBP) blood pressure (+/- SD) averaged 176 +/- 12/86 +/- 7 mmHg and 24-h SBP/DBP 151 +/- 15/81 +/- 10 mmHg. These pressures were unaltered in 51 patients in whom the baseline measurements were repeated after a further month on placebo. After the 112 patients had received placebo for 1 year (median), clinic SBP/DBP fell by 6.6 +/- 15.9 (P < 0.001)/1.4 +/- 7.4 (P = 0.06)mmHg and 24-h SBP by 2.4 +/- 10.7 mmHg (P < 0.05), whereas 24-h DBP did not change significantly. The 24-h SBP decreased more with higher baseline level and longer follow-up (5-21 months). CONCLUSIONS: These findings in older patients with isolated systolic hypertension suggest that in long-term studies the ambulatory pressure may slightly but significantly decrease on a placebo. Like those using conventional sphygmomanometry, long-term studies using non-invasive ambulatory monitoring require a placebo-controlled design.

Comparison between lovastatin and gemfibrozil in the treatment of primary hypercholesterolemia: the Finnish Multicenter Study.

A randomized, double-blind 12-week comparison of lovastatin and gemfibrozil in the treatment of patients with primary hypercholesterolemia with normal or moderately elevated triglycerides was performed in 334 patients from 19 centers in Finland. Patients with "high" total serum cholesterol (240 to 300 mg/dl) constituted Stratum 1 and patients with "very high" total serum cholesterol (greater than 300 mg/dl) constituted Stratum 2. In Stratum 1, patients were randomly assigned to either lovastatin 20 mg nightly or gemfibrozil 600 mg twice daily, and in Stratum 2 to either lovastatin 40 mg nightly or gemfibrozil 600 mg twice daily. In both strata, the lovastatin dose was doubled after 6 weeks if serum cholesterol remained greater than 200 mg/dl. Ninety-two and 93% of the patients doubled their dose in Strata 1 and 2, respectively, resulting in average doses of 38.5 mg/day (Stratum 1) and 77.4 mg/day (Stratum 1) and 77.4 mg/day (Stratum 2) by week 12. The dose of gemifibrozil was kept constant. Lovastatin reduced low-density lipoprotein (LDL) cholesterol by 31 and 42% in Stratum 1 and 2, respectively. The corresponding reductions achieved by gemfibrozil were 13 and 18%. In both strata, as well as in patients with Type IIa and IIb hyperlipoproteinemia, lovastatin was approximately 2 to 4 times as effective as gemfibrozil in lowering LDL cholesterol. Although both drugs increased high-density lipoprotein (HDL) cholesterol concentrations, gemfibrozil was 1.5 to 3 times more effective. LDL/HDL cholesterol ratios decreased significantly more during lovastatin therapy. Both drugs reduced serum triglyceride levels, but gemfibrozil was much more effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial fibrillation in older stroke patients: association with recurrence and mortality after first ischemic stroke.

OBJECTIVES: The objective of this study was to determine the association of atrial fibrillation (AF) with stroke recurrence and mortality and with the causes of death in ischemic stroke patients aged 75 years and older. DESIGN: A population-based study. SETTING: The cities of Turku and Kuopio in Finland. PARTICIPANTS: The study cohort consisted of 2635 consecutive patients aged 75 years and older, with a first ischemic stroke, registered in the FINMONICA Stroke Register. MEASUREMENTS: 28-day and 1-year stroke mortality, causes of death, and recurrence of stroke. RESULTS: There were 767 stroke patients with AF (mean age 82.2) and 1868 patients without AF (mean age 81.4). Mortality was higher in the AF group both 28 days (33.9% vs 28.1%, P = .003) and 1 year after the attack (52.7% vs 43.0%, P < .001). The age- and sex-adjusted relative risk of death at 28 days was 1.25 in the AF group (95% confidence interval (CI) 1.04-1.50, P = .018), and at 1 year it was 1.41 (95% CI 1.18-1.67, P < .001). In a Cox proportional hazards model, 1-year mortality risk comparing the AF-group with non-AF group was 1.24 (95% CI 1.10-1.39, P < .001). The strongest risk factor predicting 1-year mortality was recent myocardial infarction (MI) (RR 1.90, 95% CI 1.49-2.42). Myocardial infarction was more often the underlying cause of death in the AF group during the period of 28 days, but not from 28 days up to 1 year. The 1-year recurrence rate among those alive at day 28 was 11.5% in the AF group and 9.4% in the non-AF group (P = .240). CONCLUSION: Recent MI and AF are independent negative prognostic factors in older patients with stroke. Although the relative risk estimates attributable to AF are of the same magnitude in older as in middle-aged stroke patients, the much higher prevalence of AF in the older patients emphasizes its absolute impact on the mortality and recurrence after the first ischemic stroke in the age group 75 years and older. The treatment of coexisting cardiac disease also has the potential to prevent deaths and recurrent stroke events in older persons.