The effect of activated charcoal on drug exposure in healthy volunteers: a meta-analysis.

The objective of the study was to estimate the effect of activated charcoal (AC) administered during the first 6 h after drug intake and the effect of drug properties on drug exposure. Sixty-four controlled studies were integrated in a meta-analysis. AC administered 0-5 min after administration of a drug reduced median drug exposure by 88.4% (25-75 percentile: 65.0-96.8) (P < 0.00001). The effect of AC continued to be statistically significant when administered up to 4 h after drug intake (median reduction in drug exposure 27.4% (range 21.3-31.5%, P = 0.0006). The reduction in drug exposure was correlated with the AC/drug ratio (rho = 0.69, P < 0.0001), the volume of distribution (Vd) (rho = 0.46, P = 0.0001), and time to peak concentration (rho = 0.40, P = 0.02). We found that AC is most effective when given immediately after drug ingestion but has statistically significant effects even when given as long as 4 h after drug intake. AC appears to be most effective when given in a large dose.

Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride.

BACKGROUND: One of the controversies in preventive medicine is, whether a general reduction in sodium intake can decrease the blood pressure of a population and thereby reduce cardiovascular mortality and morbidity. In recent years the debate has been extended by studies indicating that reducing sodium intake has effects on the hormone and lipid profile. OBJECTIVES: To estimate the effects of low sodium versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol and triglycerides. SEARCH STRATEGY: "MEDLINE" and reference lists of relevant articles were searched from 1966 through December 2001. SELECTION CRITERIA: Studies randomising persons to low sodium and high sodium diets were included if they evaluated at least one of the above outcome parameters. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data, which were analysed by means of Review Manager 4.1. MAIN RESULTS: In 57 trials of mainly Caucasians with normal blood pressure, low sodium intake reduced SBP by -1.27 mm Hg (CI: -1.76; -0.77)(p<0.0001) and DBP by -0.54 mm Hg (CI: -0.94; -0.14) (p = 0.009) as compared to high sodium intake. In 58 trials of mainly Caucasians with elevated blood pressure, low sodium intake reduced SBP by -4.18 mm Hg (CI: -5.08; - 3.27) (p < 0.0001) and DBP by -1.98 mm Hg (CI: -2.46; -1.32) (p < 0.0001) as compared to high sodium intake. The median duration of the intervention was 8 days in the normal blood pressure trials (range 4-1100) and 28 days in the elevated blood pressure trials (range 4-365). Multiple regression analyses showed no independent effect of duration on the effect size. In 8 trials of blacks with normal or elevated blood pressure, low sodium intake reduced SBP by -6.44 mm Hg (CI: -9.13; -3.74) (p < 0.0001) and DBP by -1.98 mm Hg (CI: -4.75; 0.78) (p = 0.16) as compared to high sodium intake. The magnitude of blood pressure reduction was also greater in a single trial in Japanese patients. There was also a significant increase in plasma or serum renin, 304% (p < 0.0001), aldosterone, 322%, (p < 0.0001), noradrenaline, 30% (p < 0.0001), cholesterol, 5.4% (p < 0.0001) and LDL cholesterol, 4.6% (p < 0.004), and a borderline increase in adrenaline, 12% (p = 0.04) and triglyceride, 5.9% (p = 0.03) with low sodium intake as compared with high sodium intake. REVIEWER'S CONCLUSIONS: The magnitude of the effect in Caucasians with normal blood pressure does not warrant a general recommendation to reduce sodium intake. Reduced sodium intake in Caucasians with elevated blood pressure has a useful effect to reduce blood pressure in the short-term. The results suggest that the effect of low versus high sodium intake on blood pressure was greater in Black and Asian patients than in Caucasians. However, the number of studies in black (8) and Asian patients (1) was insufficient for different recommendations. Additional long-term trials of the effect of reduced dietary sodium intake on blood pressure, metabolic variables, morbidity and mortality are required to establish whether this is a useful prophylactic or treatment strategy.

Ascites fluid and plasma calprotectin concentrations in liver disease.

BACKGROUND: Calprotectin, a marker of neutrophil activation, has been associated with a poor prognosis in alcohol-induced cirrhosis. The aims were to study concentrations of calprotectin in patients with various liver diseases, and to further investigate the prognostic value of calprotectin in cirrhosis. METHODS: Plasma calprotectin concentrations were determined in 84 patients with alcohol-induced liver disease, 32 hepatitis B or C infected patients, 33 patients with liver disease of other aetiologies, 7 patients with combined aetiologies and in 24 patients with malignant disease. Thirty healthy individuals were included as controls. Ascites calprotectin concentrations were determined in patients with ascites (n = 75). Follow-up for survival was performed after a median observation period of 10 months. RESULTS: Increased plasma and ascites calprotectin concentrations were observed in malignant disease compared to non-malignant disease (P < 0.0001). Plasma calprotectin concentrations were low in viral liver disease compared to patients with non-viral liver disease (P = 0.02) and to controls (P = 0.0002). Plasma calprotectin (>median) was a highly significant marker of poor survival in alcohol-induced cirrhosis (P = 0.001), but was of no prognostic value in non-alcohol-induced cirrhosis (P = 0.88). In decompensated cirrhosis high (>upper quartile) ascites calprotectin concentrations were associated with an increased mortality (P = 0.002), as were high (>median) plasma calprotectin levels (P = 0.009). CONCLUSION: The prognostic importance of calprotectin in alcohol-induced cirrhosis is confirmed and demonstrated as specific for alcohol-induced liver disease. Low calprotectin levels are indicated in viral liver disease, and an association between high ascites calprotectin levels and malignant ascites was observed.

Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride.

BACKGROUND: One of the controversies in preventive medicine is, whether a general reduction in sodium intake can decrease the blood pressure of a population and thereby reduce cardiovascular mortality and morbidity. In recent years the debate has been extended by studies indicating that reducing sodium intake has effects on the hormone and lipid profile. OBJECTIVES: To estimate the effects of low sodium versus high sodium intake on systolic and diastolic blood pressure (SBP and DBP), plasma or serum levels of renin, aldosterone, catecholamines, cholesterol and triglycerides. SEARCH STRATEGY: "MEDLINE" and reference lists of relevant articles were searched from 1966 through December 2001. SELECTION CRITERIA: Studies randomising persons to low sodium and high sodium diets were included if they evaluated at least one of the above outcome parameters. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data, which were analysed by means of Review Manager 4.1. MAIN RESULTS: In 57 trials of mainly Caucasians with normal blood pressure, low sodium intake reduced SBP by -1.27 mm Hg (CI: -1.76; -0.77)(p<0.0001) and DBP by -0.54 mm Hg (CI: -0.94; -0.14) (p = 0.009) as compared to high sodium intake. In 58 trials of mainly Caucasians with elevated blood pressure, low sodium intake reduced SBP by -4.18 mm Hg (CI: -5.08; - 3.27) (p < 0.0001) and DBP by -1.98 mm Hg (CI: -2.46; -1.32) (p < 0.0001) as compared to high sodium intake. The median duration of the intervention was 8 days in the normal blood pressure trials (range 4-1100) and 28 days in the elevated blood pressure trials (range 4-365). Multiple regression analyses showed no independent effect of duration on the effect size. In 8 trials of blacks with normal or elevated blood pressure, low sodium intake reduced SBP by -6.44 mm Hg (CI: -9.13; -3.74) (p < 0.0001) and DBP by -1.98 mm Hg (CI: -4.75; 0.78) (p = 0.16) as compared to high sodium intake. The magnitude of blood pressure reduction was also greater in a single trial in Japanese patients. There was also a significant increase in plasma or serum renin, 304% (p < 0.0001), aldosterone, 322%, (p < 0.0001), noradrenaline, 30% (p < 0.0001), cholesterol, 5.4% (p < 0.0001) and LDL cholesterol, 4.6% (p < 0.004), and a borderline increase in adrenaline, 12% (p = 0.04) and triglyceride, 5.9% (p = 0.03) with low sodium intake as compared with high sodium intake. REVIEWER'S CONCLUSIONS: The magnitude of the effect in Caucasians with normal blood pressure does not warrant a general recommendation to reduce sodium intake. Reduced sodium intake in Caucasians with elevated blood pressure has a useful effect to reduce blood pressure in the short-term. The results suggest that the effect of low versus high sodium intake on blood pressure was greater in Black and Asian patients than in Caucasians. However, the number of studies in black (8) and Asian patients (1) was insufficient for different recommendations. Additional long-term trials of the effect of reduced dietary sodium intake on blood pressure, metabolic variables, morbidity and mortality are required to establish whether this is a useful prophylactic or treatment strategy.

Autoantibodies against interleukin 1alpha in rheumatoid arthritis: association with long term radiographic outcome.

OBJECTIVES: To investigate the possible association of interleukin 1alpha autoantibodies (IL1alpha aAb) with the long term course of joint erosion in patients with rheumatoid arthritis (RA). METHODS: Serum samples from 176 patients with RA included in a prospective study over 30 years were analysed for IL1alpha aAb by binding to human [(125)I]IL1alpha. Erosions of 19 diarthrodial joints were radiographically scored by the Larsen method. RESULTS: The relative risk (RR) of early IL1alpha aAb positive patients developing at least 30% of maximum radiographic joint destruction was significantly lower than for IL1alpha aAb negative patients, RR=0.29 (p=0.04). In rheumatoid factor positive patients RR was only 0.18 (p=0.02). Patients who seroconverted more than two years after the onset of RA showed the most aggressive development of joint erosion, with a relative risk of at least 40% of maximum radiographic joint destruction of 2.56 (p=0.048) CONCLUSIONS: The progression of radiographic joint destruction in patients with RA is associated with, and perhaps modified by, circulating IL1alpha aAb, suggesting that IL1alpha or IL1alpha aAb, or both, have a role in the erosive processes. IL1alpha aAb appear to be of prognostic significance in RA.

The association of variant mannose-binding lectin genotypes with radiographic outcome in rheumatoid arthritis.

OBJECTIVE: To investigate the possible association of mannose-binding lectin (MBL) genotypes with the outcome of rheumatoid arthritis (RA). METHODS: MBL genotypes and plasma concentrations were retrospectively determined in 140 RA patients who were selected from a major cohort followed up prospectively for up to 32 years. RESULTS: MBL-insufficient patients (those with 2 defective structural MBL alleles or with 1 defective allele combined with a low-expression variant of the normal allele) had unfavorable outcomes. The relative risk of a severe radiographic outcome event (30% of maximum radiographic destruction, or an RE30) was 3.1 (95% confidence interval 1.8-5.1) in the MBL-insufficient group versus the MBL-competent group (P < 0.0001). An RE30 occurred in 50% of MBL-competent patients within 17 years, while such an event occurred 9 years earlier in MBL-insufficient patients (i.e., within 8 years) (P < 0.0001). During the first 15 years, there was a significant trend toward lower hemoglobin levels (P < 0.04), higher erythrocyte sedimentation rates (P < 0.02), and a higher number of swollen joints (P < 0.05) in the MBL-insufficient group. CONCLUSION: MBL genotypes giving rise to MBL insufficiency are highly significant risk factors for fast progression of radiographic joint destruction.

Two edged role of mannose binding lectin in rheumatoid arthritis: a cross sectional study.

OBJECTIVE: We investigated whether polymorphisms in the gene of mannose binding lectin (MBL) may be associated with onset of rheumatoid arthritis (RA), and whether MBL in conjunction with aggregated agalactosyl IgG (IgG-G0) may be associated with clinical and paraclinical variables. METHODS: MBL genotypes and serum concentrations were measured by polymerase chain reaction and ELISA in 189 patients with established RA. Binding of purified MBL to IgG-G0 in serum was assessed and clinical and paraclinical variables were recorded. RESULTS: The median age at onset of RA in the 3 genotypes (normal: A/A, hetero: A/0, and homozygous: 0/0 for variant alleles) was 54.1 (n = 108), 47.0 (n = 68), and 38.4 years (n = 13), respectively (p = 0.01). The frequency of variant alleles in patients with onset below the median age (50.8 yrs) was 0.32, but was 0.17 in patients with onset above 50.8 years (p = 0.003) and 0.20 in 250 controls (p = 0.001). Stratification according to erosion score (no, small, large) revealed an increasing tendency among the different groups in binding of MBL to IgG-G0, increased Health Assessment Questionnaire score, and acute phase reactants in A/A individuals, while no difference was seen among carriers of variant alleles. This effect was most pronounced in those with late onset RA. CONCLUSION: Presence of MBL variant alleles was associated with early onset of RA. MBL deficiency may, therefore, accelerate the disease. However, in patients with late onset and advanced disease our results indicate that the A/A type may be associated with additional inflammation different from that seen in carriers of variant alleles.

Neopterin and interleukin-8--prognosis in alcohol-induced cirrhosis.

BACKGROUND: Neutrophil cytotoxity and activated macrophages have been implicated in the pathogenesis of alcohol-induced liver disease. The aim of this study was to relate plasma levels of neopterin, a marker of activation of the cellular immune system, and IL-8, a neutrophil chemotactic factor, with severity of liver disease and prognosis in patients with alcohol-induced cirrhosis. METHODS: Plasma concentrations of neopterin and IL-8 were assessed in 81 patients with alcohol-induced cirrhosis admitted to the Department of Medicine B, Bispebjerg Hospital, Copenhagen, Denmark, and in 16 healthy controls. After a median follow-up period of 5 years, mortality and death causes were registered. The patients were divided into groups according to the major contributing cause of death: infection, upper gastrointestinal bleeding or hepatic coma. RESULTS: Neopterin and IL-8 levels were increased in the cirrhosis patients, but not significantly related to Child-Pugh classification. Five-year mortality was 67%. High neopterin levels (>upper quartile) were an independent predictor of death (p=0.01, Log rank and p<0.02, Cox). High IL-8 levels (>upper quartile) were of no significant prognostic value for overall mortality. Causes of death related mortality were as follows (Log rank): Neopterin; p=0.009, p=0.84 and p=0.94, and IL-8; p=0.36, p=0.002 and p=0.27, respectively, according to infection, bleeding and coma as causes of death. CONCLUSIONS: Neopterin and IL-8 plasma levels are raised in patients with alcohol-induced cirrhosis, and are predictive of mortality associated with infections and upper gastrointestinal bleeding, respectively.

[The effect of reduced sodium intake on blood pressure, body weight, renin, aldosterone, catecholamines, cholesterol and triglycerides. A meta-analysis]. / Effekten af reduceret saltindtagelse på blodtryk, kropsvaegt, renin, aldosteron, katekolaminer, kolesterol og triglycerid. En metaanalyse.

The purpose of the present study was to estimate the effects of reduction in sodium intake on blood pressure, hormones and lipids. Data were extracted from randomised studies and statistically integrated in a meta-analysis. In 58 trials of hypertensive persons, a reduction in sodium intake of 118 mmol reduces systolic BP by 3.9 mmHg (CI: 3.0-4.8) (p < 0.0001) and diastolic BP by 1.9 mmHg (CI: 1.3-2.5) (p < 0.0001). In 56 trials of normotensive persons, the reduction in sodium intake reduced SBP by 1.2 mmHg (CI: 0.6-1.8) (p < 0.0001) and DBP by 0.26 mm Hg (CI: -0.3-0.9) (p = 0.12). Plasma renin and alsterone increased by a factor of three to four (p < 0.0001). There was a significant decrease in body weight and an increase in noradrenaline, cholesterol and LDL cholesterol. In conclusion the present results do not warrant a general recommendation of reducing sodium intake.

Radiographic progression in rheumatoid arthritis: a long-term prospective study of 109 patients.

OBJECTIVE: To investigate the long-term radiographic course as a mathematical function of disease duration in individual patients and in a group of patients with rheumatoid arthritis (RA). METHODS: In 109 patients with RA, radiographic examinations of 46 diarthrodial joints were performed at regular intervals of 1-3 years, for up to 30 years after disease onset. RESULTS: Five main types of progression were identified: 1) a rare type (<1%), with no radiographic progression at all; 2) a type with a slow or moderate onset, but an increasing progression rate (9% exponential growth type and 30% linear type); 3) a type with a moderate-to-fast onset and a stable progression rate (the square-root type; 11%); 4) a type with a fast onset, but a later decreasing progression rate (the first-order kinetics type, 30%); and 5) a type characterized by slow onset, then acceleration and later deceleration (the sigmoid type, 20%). CONCLUSION: The progression of radiographic damage in RA followed mathematical functions of time. The identification of progression type may be used in the prediction of outcome in patients with RA.

Effects of sodium restriction on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride: a meta-analysis.

CONTEXT: One of the controversies in preventive medicine is whether a general reduction in sodium intake can decrease the blood pressure of a population and thereby reduce the number of strokes and myocardial infarctions. In recent years the debate has been extended by studies indicating that reduced sodium intake has adverse effects. OBJECTIVE: To estimate the effects of reduced sodium intake on systolic and diastolic blood pressure (SBP and DBP), body weight, and plasma or serum levels of renin, aldosterone, catecholamines, cholesterols, and triglyceride, and to evaluate the stability of the blood pressure effect in relation to additional trials. DATA SOURCES: MEDLINE search from 1966 through December 1997 and reference lists of relevant articles. STUDY SELECTION: Studies randomizing persons to high-sodium and low-sodium diets were included if they evaluated at least one of the effect parameters. DATA EXTRACTION: Two authors independently recorded data. DATA SYNTHESIS: In 58 trials of hypertensive persons, the effect of reduced sodium intake as measured by urinary sodium excretion (mean, 118 mmol/24 h) on SBP was 3.9 mm Hg (95% confidence interval [CI], 3.0-4.8 mm Hg) (P<.001) and on DBP was 1.9 mm Hg (95% CI, 1.3-2.5 mm Hg) (P<.001). In 56 trials of normotensive persons, the effect of reduced sodium intake (mean, 160 mmol/24 h) on SBP was 1.2 mm Hg (95% CI, 0.6-1.8 mm Hg) (P<.001) and on DBP was 0.26 mm Hg (95% CI, -0.3-0.9 mm Hg) (P=.12). The cumulative analysis showed that this effect size has been stable since 1985. In plasma, the renin level increased 3.6-fold (P<.001), and the aldosterone level increased 3.2-fold (P<.001); the increases were proportional to the degree of sodium reduction for both renin (r=0.66; P<.001) and aldosterone (r=0.64; P<.001). Body weight decreased significantly, and noradrenaline, cholesterol, and low-density lipoprotein cholesterol levels increased. There was no effect on adrenaline, triglyceride, and high-density lipoprotein cholesterol. CONCLUSION: These results do not support a general recommendation to reduce sodium intake. Reduced sodium intake may be used as a supplementary treatment in hypertension. Further long-term studies of the effects of high reduction of sodium intake on blood pressure and metabolic variables may clarify the disagreements as to the role of reduced sodium intake, but ideally trials with hard end points such as morbidity and survival should end the controversy.

Mannan binding lectin in rheumatoid arthritis. A longitudinal study.

OBJECTIVE: Low serum levels of mannan binding lectin (MBL) are associated with increased risk of recurrent infections. We determined whether there was an association between serum MBL levels and the course and prognosis of rheumatoid arthritis (RA). METHODS: MBL was analyzed in sera from 99 patients with RA who were included in a longterm prospective study. RESULTS: Compared with controls, a high fraction of patients lacked detectable MBL in serum (11 vs 3%; p = 0.025). Comparing patients with MBL serum levels above and below the median revealed that those with levels below the median were younger at onset of RA (p = 0.043) and had higher erythrocyte sedimentation rate (p = 0.006), joint swelling score (p = 0.019), limitation of joint motion score (p = 0.027), and annual increase in radiographic destruction score (p = 0.053). CONCLUSION: MBL insufficiency may be a contributing pathogenetic factor in RA.

[Iron requirements and iron balance during pregnancy. Is iron supplementation needed for pregnant women?]. / Jernbehov og jernbalance under svangerskabet. Er det nødvendigt med jerntilskud til gravide?

Among fertile, nonpregnant, Danish women, 33% have absent or reduced iron stores; 22% have serum ferritin values above 70 micrograms/l, i.e., iron reserves of more than 530 mg, corresponding to the net iron losses during a normal pregnancy. During pregnancy, the demands for absorbed iron increase from 0.8 to 7.5 mg/day. Controlled studies show that iron-treated pregnant women have higher serum ferritin levels, i.e., larger iron stores, and higher haemoglobin levels than placebo-treated women. A supplement of 66 mg ferrous iron daily from the beginning of the 2nd trimester prevents iron deficiency anaemia. In Denmark, general iron prophylaxis with 60-70 mg ferrous iron daily from 20 weeks of gestation is recommended by the health authorities.

[Plasma calprotectin. A new prognostic marker of survival in alcoholic liver cirrhosis]. / Plasmacalprotektin. En ny prognostisk markør for overlevelse ved alkoholisk levercirrose.

The purpose of this study was to determine plasma concentrations of calprotectin in patients with different severity of alcoholic cirrhosis. Additionally, the prognostic value of calprotectin for recurrent infections and for survival was investigated after a median observation period of 19 months. No difference was found in calprotectin levels when comparing healthy controls (n = 16), compensated (n = 50) and decompensated cirrhotics (n = 34). However, high calprotectin concentrations (> median) was a significant prognostic marker of poor survival (p = 0.001, Log-rank test). Calprotectin levels (> median) showed an independent and much higher prognostic value than variables of liver disease (multivariate Cox model). During follow-up calprotectin levels (> median) were also a predictor of recurrent infection (p = 0.009, Log-rank test). Thus, in patients with alcoholic cirrhosis, plasma calprotectin appears to be a new prognostic marker of survival, which seems independent of severity of liver disease. Furthermore, high plasma calprotectin levels may characterize a group of cirrhotics with recurring bacterial infections.

[Iron status markers in pregnant women. No clinically significant connection between the values during the second trimester, later in pregnancy and after delivery]. / Jernstatusmarkører hos gravide. Ingen klinisk betydende sammenhoeng mellem vaerdierne i begyndelsen af andet trimester, senere i graviditeten og efter fødslen.

The aim of this randomized, double blind, placebo controlled parallel study was to evaluate whether iron status markers in pregnant women, measured early in the second trimester, could be used to predict levels later in pregnancy, and post partum. One hundred and twenty healthy pregnant women between 14 and 18 weeks of gestation were included. Sixty-three women were allocated to treatment with tablets containing 66 mg ferrous iron (as fumarate) daily, and 57 women to treatment with placebo. Haemoglobin, serum transferrin saturation, and serum ferritin were measured every fourth week during gestation, prior to delivery, one week and eight weeks post partum. Correlation matrices during pregnancy and post partum were calculated for each iron status marker, both in iron and placebo treated women. Haemoglobin, transferrin saturation and serum ferritin values at inclusion displayed steadily declining correlation coefficients with values obtained later in pregnancy. There were no clinically relevant correlations to values obtained eight weeks or less prior to delivery, or post partum. Serum ferritin values at inclusion could not be used to predict values later in pregnancy or post partum. Haemoglobin, transferrin saturation and serum ferritin values measured in the beginning of the second trimester appear unsuitable as guidelines for an individual iron prophylaxis during the remaining period of pregnancy.

No effect of the calcium antagonist, isradipine, on plasma catecholamines in irreversible chronic obstructive pulmonary disease (COPD). A randomized, double-blind, placebo-controlled study.

Calcium antagonists have been claimed to decrease the pulmonary artery pressure and increase oxygen uptake and cardiac output in patients with chronic obstructive pulmonary disease (COPD). This should tend to decrease the plasma levels of catecholamines. The purpose of the present study was to assess the effects of the vasodilating calcium antagonist, isradipine, on resting and exercise levels of catecholamines in patients with COPD. Eighteen patients with severe respiratory insufficiency (FEV1<1.01) were investigated. During maximum exercise, the baseline levels of plasma noradrenaline rose from 2.27 nmol/l (0.41-7.66: mean, range) to 3.86 nmol/l (1.3-12.2) (P = 0.0002) and plasma adrenaline rose from 0.39 nmol/l (0.07-1.02) to 0.64 nmol/l (0.07-1.77) (P = 0.0001). The patients were randomly allocated to receive either capsules of placebo or capsules of 5 mg of isradipine and were reinvestigated after 2 h and 3 months. There was no significant difference between the two groups concerning the change in plasma catecholamines, neither at rest nor at exhaustion. Furthermore, the increase in catecholamines during exercise in the two groups did not differ from each other, neither before administration of isradipine nor after. In conclusion, a vasodilating calcium antagonist did not alter the resting level or exercise induced increase in plasma catecholamines.

[Magnesium treatment of patients with acute myocardial infarction. A meta-analysis]. / Magnesiumbehandling af patienter med akut myokardieinfarkt. En metaanalyse.

The object of the study was to investigate the effect of intravenous magnesium in acute myocardial infarction. It was carried out as an overview of available randomized trials in which patients were allocated to receive either magnesium or placebo, the trials having taken place in the coronary care units of several hospitals. The subjects were 2438 patients with acute myocardial infarction in nine blind randomized trials combined in a meta-analysis and 54,822 patients in one unblinded randomized multi-centre trial. The main outcome measure was the relative chance of survival and relative chance of avoiding ventricular tachyarrhythmia. In the meta-analysis, the relative chance of survival was significantly increased in the magnesium group (RR = 1.049, 95% CI = 1.020-1.078, p < 0.0007). Hypothetically 25 papers with a mean of 271 patients and an RR of 1.0 should be included to make the result insignificant. The relative chance of avoiding ventricular tachyarrhythmia was not significantly increased in the magnesium group (RR = 1.041, 95% CI = 0.996-1.089, p = 0.07). The risk of accepting the null hypothesis (RR = 1.0) if the alternative hypothesis (RR = 1.041) is correct is 0,58 (the type 2 error). There was no effect on survival in the multi-centre study (RR = 0.996). It is concluded that intravenous treatment with magnesium increases survival in patients with acute myocardial infarction by 4.9% in nine blind trials, but has no effect in a large open multi-centre study.

Relationship between genotype, assessed by HLA typing, and phenotypic expression of iron status markers in families of 29 probands with hereditary haemochromatosis.

The purpose of this pedigree study, comprising 29 families with hereditary haemochromatosis (HH), was to evaluate the relationship between the genotype (G), based on HLA typing, and the phenotype, based on measurement of iron status markers (serum transferrin saturation and serum ferritin). Due to tight linkage between the HH locus and the HLA-A locus, 172 relatives of the 29 unrelated probands could be assigned into three groups: G0 who were considered to be normal (n = 53), G1 who were considered to be heterozygotes (n = 105), and G2 who were considered to be homozygotes (n = 14), according to whether they had no, one or two HLA haplotypes in common with the proband. A high serum transferrin saturation (> 60%) was present in 8/14 = 57.1% of the homozygotes, in 11/105 = 10.5% of the heterozygotes, and in 0/53 = 0% of the normals. Of the homozygotes, 8/14 = 57.1% had preclinical disease, 4/14 = 28.6% had clinically overt iron overload, while 2/14 = 14.3% had normal iron status markers. None of the heterozygotes had clinical evidence of iron overload. Analysis of HLA alleles and iron status markers suggested that 11/105 = 10.5% subjects initially classified as heterozygotes (G1) according to HLA typing should be reclassified as homozygotes because of abnormal iron status markers, explained by either: homozygous x heterozygous (n = 7) or heterozygous x heterozygous (n = 2) matings, HLA recombination (n = 1) or strongly abnormal iron status markers (n = 1).(ABSTRACT TRUNCATED AT 250 WORDS)

[No grounds for vasodilatory treatment in pulmonary hypertension]. / Intet grundlag for behandling af pulmonal hypertension med vasodilatation.

Large scale review of the literature on vasodilatory treatment of secondary pulmonary hypertension reveals an abundance of non-controlled and non-blinded studies. There is only a handful of randomized, placebo-controlled trials. These few studies cannot support the findings from non-controlled studies showing beneficial haemodynamic effects. Only two controlled studies showed clinically relevant parameters such as working capacity, mortality and morbidity, and vasodilators do not seem to possess beneficial influence on these parameters. It is concluded, that until now no publication has been able to convincingly demonstrate any long-term clinically beneficial effects of vasodilators in patients with secondary pulmonary hypertension.