Increased abdominal fat mass and high fat consumption in young school children with congenital heart disease: results from a case-control study.

BACKGROUND: We have previously found that infants with complex congenital heart disease (CHD) experience growth failure despite high-energy dietary supplementation. This is a follow-up and comparison with healthy controls at 9 years of age regarding body composition and macronutrient intake, especially in relationship to the diet provided during infancy. METHODS: Anthropometric changes in 10 children with CHD at 12 months and at 4 and 9 years of age were analysed as Z-scores. To assess body composition and food intake at 9 years of age, a dual-energy X-ray absorptiometry scan and a 3-day food diary were completed and compared with age- and gender-matched controls using Wilcoxon's signed-rank test for matched pairs. RESULTS: Growth changes from 12 months to 9 years, converted to Z-scores for weight for height and height for age, were significantly different within the group of children with complex CHD, although no growth differences were seen in comparison with healthy controls at 9 years of age. However, the children with CHD had statistically higher abdominal fat mass index and higher daily intake of fat, particularly from saturated fatty acid in g kg-1 compared to controls. CONCLUSIONS: At 9 years of age, children with complex CHD with growth failure and high fat intake in infancy have normalised growth but increased abdominal fat mass and higher intake of saturated fatty acid compared to their peers. Nutritional monitoring in early childhood may detect unhealthy diet quality and prevent later health risks in this group.

[Are newer antihypertensive agents better than the older ones? Results of trials (CAPPP, STOP-2, NORDIL, INSIGHT and ALLHAT) with newer antihypertensive agents]. / Er de nye antihypertensiva bedre end de gamle? Resultater fra hypertensions-studier (CAPPP, STOP-2, NORDIL, INSIGHT og ALLHAT) med nyere medikamenter.

Until recently, no morbidity-mortality study had examined the effects of "newer" drugs, like angiotensin-converting enzyme inhibitors, calcium antagonists, and alpha-blockers compared to "old", but well-proven, thiazide diuretics, and beta-blockers in the treatment of essential hypertension. The prospective and randomised clinical trials, CAPPP, STOP-2, NORDIL, INSIGHT, and one arm of ALLHAT, with a total of about 58,000 middle-aged or elderly hypertensive patients have now been published. The primary outcome, composite cardiovascular (CV) death, cerebral stroke, and myocardial infarction, or composite fatal coronary heart disease and myocardial infarction, was the same, irrespective of the drug in all trials. Thus, prevention of CV complications depends on the lowering of blood pressure with well-tolerated medication, irrespective of class.

Dietary antioxidant intake and the risk of cardia cancer and noncardia cancer of the intestinal and diffuse types: a population-based case-control study in Sweden.

In spite of diverging incidence trends, subsite, and subtype-specific gastric cancer data on the association with dietary antioxidants are sparse. We aimed to test whether the apparent protective effect of antioxidants is mainly confined to noncardia (distal) cancer of the intestinal subtype, to which most of the incidence decline in gastric cancer has been ascribed. In a Swedish study base (total population 1.3 million), we interviewed 567 cases uniformly classified to subsite (cardia vs. noncardia) and subtype (intestinal vs. diffuse), and 1165 population-based controls, frequency matched for age and sex. Serologic data on H. pylori status was available for a subset of 542 individuals. Ascorbic acid (vitamin C) was inversely associated with all subsites and subtypes of gastric cancer in a significant dose-response manner (all p<0.05), with risk reductions between 40% and 60%. beta-carotene was also strongly and negatively associated with risk, particularly with the intestinal type. The associations with alpha-tocopherol (vitamin E) were less clear. The highest parallel intake of all three antioxidants (quartiles 4), compared to those with the lowest parallel intakes (quartiles 1), was associated with a 70% lower risk of developing noncardia cancer (OR 0.3, 95% CI 0.1-0.9). Our results suggest that antioxidants might be especially beneficial among subjects at increased risk for gastric cancer such as smokers and those infected by H. pylori. We conclude that a high intake of antioxidants, as a consequence of high consumption of fruit and vegetables, may lower the risk not only for gastric cancer of the intestinal type, but also for diffuse type adenocarcinoma and cardia cancer.

Neurotransmitter aberrations in schizophrenia: new perspectives and therapeutic implications.

The dopamine hypothesis has dominated schizophrenia research for decades but is now yielding to a more diversified view, where the interaction of several neurotransmitters in complex circuitries is under scrutiny. Especially, glutamatergic and serotonergic mechanisms are attracting attention. However, the role of dopamine also needs further exploration and may still turn out to have novel therapeutic applications. In the present minireview an attempt is made to integrate preclinical and clinical data on neurotransmitter aberrations in schizophrenia and to discuss their therapeutic implications.

Human milk kappa-casein and inhibition of Helicobacter pylori adhesion to human gastric mucosa.

Readily digested caseins, which account for almost half of the protein content in human milk, are important as nutritional protein for breast-fed infants. It has also been advocated that part of the antimicrobial activity of human milk resides in the caseins, most likely the glycosyated K-casein. Top explore this possibility, we purified K-casein from human milk to homogeneity by a two-step size-exclusion chromatography procedure. Purified human K-casein, in contrast to K-casein purified from bovine milk, effectively inhibited the cell lineage-specific adhesion of fluoroisothiocyanate-labeled Helicobacter pylori to human gastric surface mucous cells. The inhibitory activity was abolished by metaperiodate oxidation and considerably reduced by preincubation with alpha-L-fucosidase but not with alpha-N-acetylneuraminidase or endo-beta-galactosidase. These results strongly support the view that fucose containing carbohydrate moieties of human K-casein are important for inhibition of H. pylori adhesion and, thus, infection. They also suggest that breastfeeding may protect from infection by H. pylori during early life and that species-specific glycosylation patterns, as illustrated by human bovine K-casein, partly determine both the narrow host spectrum of this human gastric pathogen and the capacity to resist infection.

ACE inhibition preserves renal function better than beta-blockade in the treatment of essential hypertension.

Antihypertensive treatment can slow down the decline in glomerular filtration rate (GFR) with time. In patients with diabetic nephropathy, angiotensin converting enzyme (ACE) inhibition has been shown to be more effective in this regard than conventional antihypertensive therapy. Whether this applies to the much larger population of patients with essential hypertension is not yet known. In the present study, the effects of two different antihypertensive therapies on the loss of GFR with time, determined with Cr51-EDTA clearance after 6, 12 and 24 months of treatment, were assessed in a prospective, randomised, double-blind trial in 257 patients with essential hypertension. All had normal renal function and none had diabetes mellitus or glucosuria. Proteinuria (dipstick positive or trace) was detected in 7 patients initially. The two therapeutic modalities were the ACE inhibitor cilazapril and the beta-adrenoceptor blocking agent atenolol. Both therapies were equally effective in lowering systolic blood pressure (e.g. from 168 mmHg to 152 mmHg with cilazapril and from 170 mmHg to 155 mmHg with atenolol after 6 months, p < 0.001 for both). However, atenolol was slightly but significantly more effective in lowering the diastolic blood pressure at 6, 12 and 24 months. The decline in GFR with time was significantly smaller with cilazapril than with atenolol. After 6 months the reduction in GFR was 1.0 vs. 4.0 ml/min x 1.73 m2, p = 0.008 (cilazapril vs. atenolol) and after 12 months the corresponding changes were 2.0 vs. 4.5 ml/min x 1.73 m2, p = 0.04 and after 24 months 3.0 vs. 4.0 ml/min x 1.73 m2, respectively (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of angiotensin-converting enzyme inhibition versus conventional antihypertensive therapy on the glomerular filtration rate.

Antihypertensive treatment has been shown to slow down the decline in glomerular filtration rate (GFR) with time. This has been most extensively studied in patients with diabetic nephropathy and, to some extent, with other forms of renal disease. Angiotensin-converting enzyme (ACE) inhibition has been shown to be more effective in this regard than conventional antihypertensive therapy. This important aspect of antihypertensive treatment has not been studied previously in patients with essential hypertension. Preliminary results regarding the effects of two different antihypertensive therapies on the loss of GFR with time, determined with 51Cr-EDTA clearance after 6, 12, and 24 months of treatment, are presented here. The GFR was assessed in a prospective, randomized, double-blind trial in 257 patients with essential hypertension. All had a normal renal function, and none had diabetes mellitus or glucosuria. The two therapeutic modalities were the ACE inhibitor cilazapril and the beta-adrenoceptor blocking agent atenolol. Both therapies were equally effective in lowering the systolic blood pressure. However, atenolol was slightly but significantly more effective in lowering the diastolic blood pressure after 6, 12, and 24 months. The decline in GFR with time was significantly smaller with cilazapril than with atenolol. After 6 months, the reduction in GFR was 1.0 (cilazapril) vs. 4.0 (atenolol) ml/min x 1.73 m2 (p < 0.01). After 12 months the corresponding changes were 2.0 vs. 4.5 ml/min x 1.73 m2 (p < 0.05) and after 24 months 3.0 vs. 4.0 ml/min x 1.73 m2 (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of inhaled lignocaine and adrenaline on capsaicin-induced cough in humans.

BACKGROUND: The hypothesis that adrenaline can augment and/or prolong the antitussive effect of nebulised lignocaine was examined. METHODS: The effect of inhaled lignocaine alone (20 mg) and in combination with adrenaline (400 micrograms) was studied on capsaicin-induced cough in 10 healthy subjects. RESULTS: Cough was significantly reduced between five and 25 minutes by lignocaine. Adrenaline alone had no inhibitory effect and it neither augmented nor prolonged the antitussive effect of lignocaine. The subjective anaesthesia by lignocaine was short lasting (less than 15 minutes) and not altered by adrenaline, suggesting different sensory mechanisms for anaesthesia and cough suppression. Plasma concentrations of lignocaine were low (< 30 ng/ml), not altered by adrenaline, and did not correlate with the local anaesthetic or the antitussive effect. CONCLUSIONS: Lignocaine acts locally in the oropharynx and airways and adrenaline does not alter the effect or absorption of nebulised lignocaine on the human respiratory mucosa.

Separation of active and inactive forms of recombinant human plasminogen activator inhibitor type 1 (PAI-1) expressed in Chinese hamster ovary cells: comparison with native human PAI-1.

Human plasminogen activator inhibitor type 1, PAI-1, was expressed in Chinese hamster ovary cells. A production level of 10-15 mg latent PAI-1 per liter of media was achieved after methotrexate amplification. Latent recombinant PAI-1 was purified by two chromatographic steps, cation exchange chromatography on CM-Sepharose and affinity chromatography on heparin-Sepharose. The obtained latent PAI-1 was approximately 90-95% pure showing one homogenous peak upon size-exclusion chromatography. However, four different isoforms due to different degrees of sialylation could be seen upon isoelectric focusing. Purified latent PAI-1 was activated by incubation in 6 M guanidine-HCl. By this method, 40-60% of PAI-1 was converted to an active form after removing the denaturant. The active fraction of PAI-1 was separated from inactive material by size exclusion chromatography on Superdex 200. Active PAI-1 migrated as expected for a 43-kDa large protein, while inactive PAI-1 migrated as larger protein complexes, suggesting that the remaining inactive PAI-1 was in the form of aggregates. This method for the separation of active and inactive PAI-1 could also be used for activated native PAI-1 prepared from human endothelial cells. Active recombinant PAI-1 was remarkably stable at pH 5.5, both when stored on ice and when stored at room temperature.

Nutrients and gastric cancer risk. A population-based case-control study in Sweden.

A population-based case-control study of gastric cancer was conducted in areas with contrasting incidence rates in Sweden. Face-to-face interviews were carried out with 338 (74.1%) of all eligible cases and 679 (77.3%) of the selected controls. Consumption of selected nutrients during adolescence and 20 years prior to interview was estimated, together with life-time intake of vitamin supplements. Ascorbic acid and beta-carotene had an unequivocal protective effect, but alpha-tocopherol and nitrate were also negatively associated with gastric-cancer risk. In a multivariate analysis including all of these factors, only ascorbic acid remained a significant protective factor. The only macronutrient positively associated with the risk of gastric cancer was fat: intake 20 years prior to interview, but not during adolescence, was found to have a significant impact. Supplementation with vitamins almost halved the risk after adjustment for dietary intake of the corresponding vitamins. While the protective effect of vitamin C and beta-carotene could conceivably be ascribed to other agents in the diet, the strong negative association between supplementation with vitamin C and risk of gastric cancer supports the hypothesis of a protective role of this anti-oxidant.

Effect of coffee on ambulatory blood pressure in patients with treated hypertension.

Effects of caffeine on ambulatory blood pressure, heart rate, renin-angiotensin system, and ANP were studied in patients treated for mild to moderate hypertension in a randomized, double-blind, placebo-controlled, cross-over trial comparing 2 weeks of caffeine-free diet with 2 weeks of regular coffee use. Twenty-three patients (13 men; aged 28-74 years) with treated, mild to moderate essential hypertension and a regular intake of 3-4 cups of coffee daily completed the study. Mean 24-h, day- or night-time ambulatory blood pressure and heart rate were not different between regimens. Nor were there any effects on the renin-angiotensin system while ANP was significantly increased during caffeine intake. Compliance of the dietary regimen was excellent as assessed by serum caffeine concentration measurements. We conclude that habitual coffee drinking did not influence the 24-h blood pressure profiles or cardiovascular hormones in treated hypertensives.

Antihypertensive efficacy and side effects of three beta-blockers and a diuretic in elderly hypertensives: a report from the STOP-Hypertension study.

OBJECTIVE: To compare the blood pressure-lowering efficacy, the frequency of side effects and changes in laboratory values of three beta-blockers and a potassium-sparing diuretic combination in elderly hypertensive patients. DESIGN: The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was a prospective, randomized, double-blind, multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70-84 years. METHODS: The study group consisted of 1627 elderly hypertensive patients (mean +/- SD age 75.7 +/- 3.7 years; 37% males, 63% females). Supine and standing blood pressure, heart rate and side effects were recorded at each visit. Blood was drawn for routine analysis. The mean length of follow-up was 25 months (range 6-65). No patient was lost to follow-up. RESULTS: After 2-months' single-drug therapy, all four active drugs were found to be equally effective in reducing diastolic blood pressure (DBP). However, there were differences in their efficacy in reducing systolic blood pressure (SBP); the diuretic was significantly more effective than the beta-receptor blockers. The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate. More than two-thirds of the patients were given supplementary treatment, most of them already by the 2-month visit, after which there was no significant difference in blood pressure among the treatment regimens. The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens. CONCLUSION: Metoprolol (controlled release), atenolol, pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP. There were differences in their efficacy in reducing SBP, the diuretic being more effective than the beta-blockers. After addition of supplementary treatment (beta-blocker to diuretic, or vice versa) there were no significant differences in blood pressure reduction among the groups. The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens. Thus, the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs.

Capsaicin-induced cough in humans.

We have evaluated the properties of capsaicin as a selective cough-inducing agent in healthy human subjects. Despite frequent coughing, the subjects could inhale repeated breaths of capsaicin aerosol during 60 s without difficulty. Cough started immediately on inhalation and was most intense during the first 30 s. Cough always disappeared promptly when the capsaicin inhalation was terminated. The cough response was well reproducible and concentration-dependent up to 10 microM; at higher concentrations there was a distinct plateau of the cough response. Specific airway conductance was not changed 3 min after 50 microM capsaicin. Capsaicin (> or = 10 microM) had a burning taste, but there were no visual signs of pharyngitis or laryngitis. Citric acid (nebulized solutions 0.125 to 32%) had a choking effect and could be administered only as single breaths. There was no correlation between the cough response to citric acid and to capsaicin. Inhaled lidocaine (20 and 80 mg from nebulized solutions) caused a dose-dependent inhibition of capsaicin-induced cough. Lidocaine suppressed citric acid-induced cough as effectively as capsaicin-induced cough. In conclusion, we have characterized capsaicin-induced cough and demonstrated that it can be a useful tool in the study of cough reactivity and for evaluation of antitussive agents in humans. Capsaicin may be complementary to citric acid and may offer experimental advantages over this traditional tussive stimulus.

Atomic absorption spectrometric determination of selenium in human blood components.

We separated blood from five healthy blood donors into plasma, erythrocytes, platelets, and leukocytes; counted the number of cells in each fraction; and determined the selenium content of each component by hydride generation atomic absorption spectrometry. The mean (+/- SD) selenium concentrations and amounts measured were as follows: whole blood 102.3 +/- 16.1 micrograms/L, plasma 76.9 +/- 10.6 micrograms/L, erythrocytes 13.7 +/- 2.8 ag per cell, platelets 4.8 +/- 1.1 ag per cell, and leukocytes 99 +/- 26 ag per cell.

Determination of selenium in fish flesh by hydride generation atomic absorption spectrometry.

Selenium was determined in freeze-dried fish flesh from perch, pike-perch and the fish flesh reference materials MA-A-2 No. 1174 and MA-B-3 No. 151 (both from the International Atomic Energy Agency) by hydride generation atomic absorption spectrometry. Four different decomposition procedures were tested. They yielded consistent results for the four specimens, but the certified concentration level of selenium in the reference material MA-A-2 was not reached. This indicated losses or the presence of very stable selenium-containing compounds in this fish flesh. Neutron activation analysis of the reference material, however, was in agreement with those results obtained.

Fluorimetry of selenium in body fluids after digestion with nitric acid, magnesium nitrate hexahydrate, and hydrochloric acid.

A digestion procedure involving nitric acid, magnesium nitrate hexahydrate, and hydrochloric acid suffices for selenium determinations in whole blood, serum, and urine by molecular fluorescence spectrometry. To test the accuracy of the method we compared the results with those from hydride-generation atomic absorption spectrometry, and we also analyzed reference materials.

Antihypertensive effect of felodipine or hydralazine when added to beta-blocker therapy.

In a double-blind randomized study, hydralazine (n = 59) or the new dihydropyridine calcium antagonist felodipine (n = 61) was added to previous treatment with beta-adrenoceptor blocking agents in a group of 120 patients with essential hypertension. Active treatment with either hydralazine or felodipine was given for 8 weeks after a 4-week placebo run-in period, at the end of which all patients had supine diastolic blood pressures greater than 95 mm Hg. Assessment of the results according to the intention to treat principle showed that felodipine was significantly more effective than hydralazine at the doses employed, reducing systolic blood pressure 10-19 mm Hg more than hydralazine and reducing diastolic blood pressure 5-11 mm Hg more than hydralazine (95% confidence intervals). The number of patients complaining of side effects, the number of complaints, and the number of patients that had to be withdrawn from treatment were numerically higher during treatment with hydralazine than with felodipine, but these differences were not statistically significant. Against this background it is concluded that felodipine is superior to hydralazine when added to an antihypertensive regimen consisting of beta-adrenoceptor blocking agents.

Regression of structural alterations of hypertension with calcium antagonists--vascular hypertrophy.

Structural vascular changes in the precapillary arterioles are a cardinal feature of established hypertension, and have been described in several vascular beds. In brief, the wall:lumen ratio becomes increased due to hypertrophy of the vascular smooth muscle cells. This results in a reduction of the inner radius in the precapillary vessels, which causes a structurally based vascular hyperreactivity and accentuates the increase in systemic vascular resistance, another hallmark of established hypertension. Much interest has been devoted to the possibility of obtaining a regression of these structural vascular changes. Previously, the emphasis was on obtaining a fall in blood pressure, but more recently additional factors have also been considered, in particular the so-called trophic factors. In this context the calcium antagonists of the dihydropyridine type appear to be of particular interest, since these are markedly effective in lowering elevated arterial pressure, while at the same time they do not cause reflex-mediated elevations of trophic factors during long-term treatment. Few clinical data are yet available to show whether calcium antagonists can cause a regression of structural vascular changes, but some recent animal work suggests that they are clearly useful in this respect.

Alterations in trace element and plasma amino-acid profile in experimental gram-negative septicaemia.

Infection can produce changes in the levels of trace metals such as copper, iron and zinc and several amino acids. These trace metals are involved in many metabolic reactions as well as in the host defence response. In the present study we have induced septicaemia in male Sprague-Dawley rats. The rats were made septic by surgical insertion of a gelatine capsule containing known amounts of E. coli (1.25 x 10(7) bact/ml) and Bacteroides fragiles (2.5 x 10(7) bact/ml) along with sterile rat faeces as an adjuvant (50% vol/vol), and barium sulphate (10% weight/weight) as an irritant into the abdomen. Blood samples were collected at 36, 60 and 72 h to study alterations in the pattern of copper, zinc, calcium and magnesium and plasma amino acids. Liver samples were taken after sacrifice at 72 h for inorganic element analysis. Sepsis produced a significant increase in copper and magnesium and a significant decrease in zinc and calcium levels of plasma. Trace element content of the livers the septic rats did not differ appreciably from control rats. Septic rats also had a lowered concentration of branched chain amino acids. These changes especially those of copper and zinc could be expected to have a role in the progress of the disease. The changes observed in the present study might be caused through the release of Interleukin-I or related substances from the phagocytic cells.

Controlled trial of nifedipine and bendroflumethiazide in hypertension.

In a double-blind study 30 patients with mild or moderate (World Health Organization classification I or II) hypertension were treated with either nifedipine, 20 mg twice a day, or bendroflumethiazide, 2.5 mg (+0.57 g KCl) twice a day for 24 weeks. All patients were then given a combination of half the initial dosage of both drugs for an additional period of 6 weeks. Nifedipine caused a significant reduction of both supine and standing blood pressures (16/10 and 11/5 mm Hg, respectively). Bendroflumethiazide also reduced both recumbent and standing blood pressures significantly (15/10 and 11/10 mm Hg, respectively). Combined treatment with nifedipine and bendroflumethiazide caused a further reduction of both supine and standing blood pressures. The total reduction compared with placebo was 23/12 mm Hg (p less than 0.001) and 17/11 mm Hg (p less than 0.001), respectively. There was no significant correlation between antihypertensive effect and age of patient.