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Biomedical subjects

H Holm

Publications and source records attributed to H Holm.

At least 19 recordsLinked to original sources

Pharmacokinetics and pharmacodynamics of mivacurium in young adult and elderly patients.

BACKGROUND: Mivacurium is hydrolyzed by plasma cholinesterase, and is therefore less dependent on liver metabolism and renal elimination than other neuromuscular blocking drugs. This might favor the use of mivacurium in elderly patients. The purpose of this study was to compare the pharmacodynamics and the pharmacokinetics of the three isomers of mivacurium and their metabolites in young adult and elderly patients. METHODS: Sixty-four patients were included in a dose-response study, in which 32 young adults and 32 elderly patients received one of four doses of mivacurium. An additional bolus dose of mivacurium to a total of 0.1 mg/kg was given followed by a continuous infusion adjusted to maintain a 91-99% neuromuscular block. The times to maximum block and different levels of recovery were measured using mechanomyography and train-of-four (TOF) nerve stimulation. Thirty-two patients were randomly selected for the pharmacokinetic study. Venous samples were taken for determination of the three mivacurium isomers and the metabolites. RESULTS: The estimated ED95 were 0.053 and 0.061 mg/kg in young adults and elderly patients, respectively (NS). The median infusion rate did not differ, but duration to a TOF ratio of 0.7 was significantly longer in elderly patients than in young adult patients (21.0 vs. 16.5 min). No statistically significant difference between the age groups in clearance and elimination half-life of the isomers was seen. The half-lives of the metabolites were significantly prolonged in the elderly patients. CONCLUSION: There were no significant differences in the potency or infusion requirements between the adult and elderly patients, but the rate of recovery was significantly, though only moderately prolonged, in the elderly patients. No significant difference in clearance was seen but the elimination half-lives of the metabolites was longer in the elderly patients.

Adolescent↗

Inadequate treatment of depression after myocardial infarction.

OBJECTIVE: The objective of the study was to investigate the prevalence of depressive symptoms and the self-reported psychiatric treatment after myocardial infarction. METHOD: Depressive symptoms and medication were studied in 85 consecutive acute myocardial infarction patients during 18 months follow-up. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). RESULTS: The proportion of patients with depressive symptoms (BDI >/= 10) was 21.2% while in hospital, 30.0% at 6 months and 33.9% at 18 months. At 18 months, none of the patients were receiving adequate antidepressive medication. There were eight patients with BDI scores corresponding to moderate/severe depression (BDI >/= 19). Six of these patients were receiving benzodiazepine medication and two of them had been treated in the mental health care system after the myocardial infarction. CONCLUSION: There seems to be considerable problems in the diagnosis and/or treatment of depression after myocardial infarction.

Aged↗

Promoting breastfeeding in rural Gambia: combining traditional and modern knowledge.

Sub-optimal breastfeeding practices still prevail in many countries, especially in traditional rural communities. Despite high breastfeeding initiation rates and long total duration of breastfeeding, exclusive breastfeeding is a rare practice. In the present study, quantitative methods were used to identify current infant feeding practices in 12 rural communities in The GAMBIA: Results indicated that delayed initiation of breastfeeding, prelacteal feeding and failure to practice exclusive breastfeeding were widespread. Qualitative data further indicated that current beliefs and practices were strongly influenced by traditional beliefs and practices. These were kept very much alive by elders, both women and men, including husbands. The results also showed an unexpected support for bottle-feeding from both male and female elders who considered it part of the modernization process. A strategy for promoting early initiation of breastfeeding, feeding of colostrum and exclusive breastfeeding for 6 months in rural communities should therefore incorporate traditional beliefs and practices into modern messages on optimal breastfeeding. Traditional beliefs and practices in the study setting that could be used in this way included knowledge from the population's acquaintance with the newborns of their livestock. It also included the traditional practice of mothers taking their very young children with them when going to work in the fields. The paper suggests such a strategy by developing a matrix to establish linkages between modern and traditional knowledge on a specific practice. Such linkages facilitate the acceptance of recommendations on infant feeding by mothers in these communities. The strategy recommends an expanded target group to include elders and husbands, as the data show that these groups are highly influential in matters regarding patterns of child feeding.

Adult↗

Proteinase inhibitors induce selective stimulation of human trypsin and chymotrypsin secretion.

Among the variety of signals stimulating pancreatic secretion, cholecystokinin (CCK) and related hormones are assumed to be responsible for modulating proteinase output. In some species, intraduodenal tryptic activity has to be abolished to demonstrate feedback-induced CCK release. The aim of this study was to investigate in vivo effects of modest inhibition of intraduodenal proteolytic enzymes on the secretion patterns of pancreatic enzymes and plasma CCK concentrations. Two inhibitors (Kunitz trypsin inhibitor and Bowman-Birk inhibitor) were applied. Intermittent sampling of plasma nd duodenal juice was performed during intraduodenal saline and inhibitor instillations in six healthy volunteers. Enzyme activities and concentrations were determined in the duodenal samples and expressed as percentage of basal values. Instillation of Kunitz trypsin inhibitor caused an increase in trypsin and the pancreatic secretory trypsin inhibitor (PSTI), without changes in plasma CCK. This result demonstrates, for the first time, that pancreatic exocrine secretion of trypsin and chymotrypsin is regulated by different mechanisms. Bowman-Birk inhibitor additionally stimulated the secretion of chymotrypsin and carboxypeptidase A and B and increased plasma CCK. Elastase 1 and amylase secretions were not increased by either instillations. Although the inhibitors have similar in vitro inhibition patterns, their in vivo effects are different. The nonparallel secretion of proteinases (trypsin, chymotrypsin and elastase 1) supports the view of a complex system involved in feedback regulation of human pancreatic exocrine secretion, including signals other than CCK.

Adult↗

Inhibitor-stimulated non-parallel pancreatic secretion in man: hormonal and neural regulation?

BACKGROUND: We wanted to study whether a total inhibition of tryptic activity in the duodenum would induce a cholecystokinin (CCK)-dependent increase in pancreatic exocrine proteinase secretion. METHODS: Concentrations of CCK and activities and concentrations of pancreatic enzymes were measured in human plasma and duodenal juices, respectively, collected during continuous intraduodenal instillations of proteinase inhibitors, with and without intravenous atropine administration. RESULTS: Inhibitor instillation totally abolished tryptic activity and reduced the chymotryptic and elastase (1 and 2) activities by 95-100%. The inhibitors caused a rapid increase in the concentrations of trypsin, chymotrypsin, and pancreatic secretory trypsin inhibitor (PSTI) but had only a slight or no effect on amylase and elastase 1 secretion. An enhanced secretion of PSTI lends support to a possible connection between PSTI (resembling the monitor peptide causing CCK release in rats) and the enzyme secretion in man. CCK increased from 7 to 12-13 pmol/l. Intravenous atropine almost completely blocked the inhibitor-stimulated enzyme and PSTI secretion and reduced amylase activity by 50%. A further significant (P = 0.002) increase in the inhibitor-induced CCK output was found during atropine administration, as compared with the test situation without atropine. CONCLUSION: The inhibitor-induced pancreatic secretion during total inhibition of tryptic activity shows a non-parallel secretion requiring different signals for different enzymes. The increase in plasma CCK levels indicates that CCK is feedback-regulated by both an inhibitor-mediated decrease in duodenal enzyme activity and a further decrease in pancreatic enzyme secretion by atropine.

Atropine↗

Update on newer neuromuscular blocking drugs.

The development of new non-depolarizing neuromuscular blocking drugs starting with the introduction of the intermediate-acting agents atracurium and vecuronium has made it possible to avoid the use of succinylcholine for elective cases. Recently 4 new drugs have become available; the short-acting mivacurium, the intermediate-acting rocuronium and the 2 long-acting drugs doxacurium and pipecuronium. The pharmacokinetic and pharmacodynamic profile of these drugs are reviewed in this paper.

Adult↗

Platelet selenium as indicator of wheat selenium intake.

The effect of an increased intake of wheat selenium (Se) on platelet Se, serum Se, whole-blood Se, and glutathione peroxidase (GSH-Px) levels was investigated in 14 healthy Norwegian females (age 21-53 years). The intake of 60 micrograms Se per day as wheat Se, for six weeks, significantly increased the platelet Se (mean +/- SEM) from 9.1 +/- 1.1 mumol/L to 11.4 +/- 0.9 mumol/L, the serum Se from 1.43 +/- 0.18 mumol/L to 1.63 +/- 0.25 mumol/L, and the whole blood Se from 1.77 +/- 0.18 mumol/L to 2.01 +/- 0.18 mumol/L. The increase in percent of initial Se values was twice as high for platelets as for serum and whole blood. The GSH-Px levels were not altered during the experiment. Platelet Se was not significantly correlated to the Se intake initially. At the end of the experimental period, the Se in platelets reflected the total Se intake, but not with a simple linear correlation. No significant correlation between the total Se intake and the Se concentration in whole blood or serum was found.

Adult↗

Nicotine intake and dependence in Swedish snuff takers.

Two studies examining nicotine intake in users of Swedish moist oral snuff are reported. Absorption form a single pinch (2 g) in ten users after overnight abstinence was fairly rapid. The increment in plasma nicotine concentrations averaged 9.9 ng/ml (SD 6.5) after 10 min and peaked at 14.5 ng/ml (SD 4.6) shortly after discarding at 30 min. Among groups of habitual snuff takers (n = 27) and cigarette smokers (n = 35) studied on a day of normal snuffing/smoking, peak blood nicotine levels after use were similar [averaging 36.6 ng/ml (SD 14.4) and 36.7 ng/ml (SD 16.1), respectively], but there was a tendency to higher cotinine levels in the snuffers (399.2 ng/ml versus 306.3 ng/ml). The snuff takers and cigarette smokers reported similar levels of subjective dependence on tobacco. Epidemiological study of Swedish snuff users could clarify whether the cardiovascular risks of tobacco are attributable to nicotine or to other smoke components, as in their case nicotine intake is not accompanied by combustion products.

Adult↗

L-tryptophan supplementation does not improve running performance.

In 1988 Segura and Ventura (14) reported that 1.2 g of L-Tryptophan (L-TRY) supplementation increased total exercise time by 49.4% when the subjects were running at 80% of maximal oxygen uptake (VO2max). In human performance research, acute improvements of that category are rather uncommon. Both for this reason and because ingestion of purified L-TRY may have adverse effects, it seemed pertinent to repeat the investigation of Segura and Ventura. Forty-nine well-trained male runners, aged 18-44, with an average maximal aerobic power of 66 (57-78) ml.kg-1.min-1, participated in a randomized double blind placebo (P) study. Each subject underwent four trials on the treadmill. The first two served as learning experience, including measurement of VO2max and anaerobic threshold. During the last two trials the subjects ran until exhaustion at a speed corresponding to 100% of their VO2max-first an initial trial and then after receiving a total of 1.2 g L-TRY or P over a 24 hour period prior to the run. No significant difference between the improvements in the L-TRY and P group could be demonstrated. It is concluded that oral L-TRY supplementation does not enhance running performance.

Adolescent↗

Supplementation with wheat selenium induces a dose-dependent response in serum and urine of a Se-replete population.

In spite of a rather modest dietary intake of selenium (80 micrograms/10 MJ), Norwegian serum Se levels are among the highest in Europe. As part of an ongoing study of Se bioavailability, effects of different doses of wheat Se were investigated in eighteen healthy, Norwegian women. The participants were given Se-rich bread providing 100, 200 and 300 micrograms Se daily for 6 weeks. About 50% of the Se intake was excreted in the urine by week 6, compared with 67% before the intervention started. Serum Se increased by 20, 37 and 53 micrograms/l respectively, in the three group (P less than 0.001). The blood response and renal clearance results compare well with data obtained from less Se-replete populations, and support the hypothesis that selenomethionine from the diet is incorporated into a non-specific amino acid pool. Our study indicates that the intake of wheat Se is the main determinant of blood Se levels in Norway.

Adult↗

Raw soybeans stimulate human pancreatic proteinase secretion.

Intraduodenal instillation of raw soybeans stimulated pancreatic proteinase secretion in humans. Raw soybeans almost abolished the activity of chymotrypsin and severely reduced (50%) the tryptic activity. Immunoreactive tryptic and chymotryptic material simultaneously appeared in amounts 2 to 4 times basal concentrations. This increase, demonstrated with rocket immunoelectrophoresis, was begun within the first 10 min of soybean instillation. The enhanced secretion also persisted throughout the succeeding saline instillation, and it is suggested that the presence of Kunitz trypsin inhibitor contributed to this postprandial stimulation. An amidase that hydrolyzes low-molecular-weight substrates (i.e., benzoyl-arginine p-nitroanilide) was found in raw soybeans. Its low activity was not assumed to substantially bias standard trypsin assays. The increased proteinase secretion was, as previously published, not preceded by an elevated plasma cholecystokinin concentration. The raw soybeans also caused a nonparallel secretion of amylase and proteinases. Nervous, perhaps cholinergic, regulation mediates the inhibitor-stimulated proteinase secretion in humans. This stimulation yields both a general increase of proteinases and also a specific inhibitor-resistant trypsin. This is consistent with the physiologic need for proenzyme-activation in the presence of inhibitors and for restoration of the proteolytic capacity of the duodenal juice.

Amylases↗

Seasonal siderosis in female eider nesting in Svalbard.

Specimens of female and male eider (Somateria mollissima) were collected in Svalbard. Atomic absorption analyses revealed mean hepatic iron concentrations of 280 micrograms per g wet weight 2 to 3 weeks before egg laying, 2620 micrograms per g after 2 to 3 weeks brooding and 800 micrograms per g 2 weeks after hatching. At the highest concentration, there was massive siderosis with the iron located in both parenchymal and non-parenchymal cells. No signs of liver injury were seen. The female eider fasts completely from the start of egg laying to the end of hatching. The non-parenchymal iron deposits are probably the result of catabolism of blood and lean tissue, i.e., translocation of body iron. The parenchymal siderosis can hardly be explained by liver weight loss alone. An increased iron absorption preceding the egg laying is suggested.

Animals↗

Opposite effect of cold on energetic efficiency in normal and obese Wistar rats with hypothalamic lesions.

Reduced thermogenesis in brown adipose tissue (BAT) may contribute to increased energetic efficiency and obesity in rats with ventromedial hypothalamic (VMH) lesions. Thermogenic activity of BAT is a function of the environmental temperature. If a relationship exists, it follows that the increased energetic efficiency of VMH-lesioned rats likewise should be governed by temperature. We have therefore investigated the energy balance of normal and VMH-lesioned rats housed at 30 degrees C and 10 degrees C. Experiments at differing feeding levels allowed calculation of maintenance energy requirements and the net energetic efficiencies of each group. VMH-lesioned rats at thermoneutrality (30 degrees C) accumulated more body fat at all feeding levels than did normal rats. Maintenance energy requirement was reduced, but the net energetic efficiency did not differ significantly from normal. The reduced maintenance energy requirement of lesioned rats persisted at 10 degrees C. Net energetic efficiency decreased in normal rats acclimated to cold but increased in the lesioned group. The difference was significant (P less than 0.05). The cold-induced increase in interscapular brown adipose tissue (IBAT) oxidative capacity of VMH-lesioned rats was only half that of normal rats. Differences in BAT thermogenesis may be the basis for the differing temperature effects on net energetic efficiency.

Adipose Tissue↗

Raw soy and purified proteinase inhibitors induce the appearance of inhibitor-resistant trypsin and chymotrypsin activities in Wistar rat duodenal juice.

Rats were fed raw soybeans or purified soybean proteinase inhibitors by tube to see whether they were able to produce inhibitor-resistant trypsin, as previously demonstrated in humans. Their duodenal chyme contained only 20-50% of the enzymatic activities of animals fed bovine serum albumin (BSA) as test protein. However, both tryptic and chymotryptic activities had considerable resistance to low- and high-molecular-weight inhibitors of serine proteinases. In particular, the tryptic activity demonstrated a high degree of inhibitor resistance. Human alpha 1-antitrypsin and lima bean inhibitor in amounts that inhibited bovine serum albumin-induced trypsin completely caused only 2-12% inhibition of the raw soybean-induced tryptic activity. The inhibitor-resistant tryptic and chymotryptic activities after raw soybean instillation might be caused by the Bowman-Birk and Kunitz trypsin inhibitors. The physiologic significance of an inhibitor-resistant trypsin might be to assure activation of other pancreatic proenzymes. The results of the present rat experiments confirm the previous findings of inhibitor-resistant trypsin in humans.

Animals↗

Characterization of a human trypsin resistant to Kunitz soybean trypsin inhibitor. Studies of duodenal juices after tube instillation of raw soybean extract.

Human duodenal juices collected during tube instillation of raw soybean extract into the duodenum contained free trypsin and free Kuntiz soybean trypsin inhibitor (KTI) in the simultaneous presence of trypsin-KTI complexes. It has previously been suggested that this KTI-non-inhibitable trypsin has a general resistance to serine protease inhibitors. Four different trypsin forms have been found and partly characterized by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and isoelectric focusing followed by Western immunoblotting or enzyme staining. In addition, crossed immunoelectrophoresis and affinity chromatography with antibody-coupled gels have been used for identification of free and inhibitor-complexed trypsin.

Blotting, Western↗

Bioavailability of oral magnesium supplementation in female students evaluated from elimination of magnesium in 24-hour urine.

The bioavailability of Mg from different preparations after oral intake has been evaluated by measuring the Mg elimination in 24-hour urine during placebo and treatment periods in 18 normal female students receiving 15-20.6 mmol/day. The urine elimination was increased 0.9-1.3 mmol/24 h by (a) tablets containing Mg citrate/Mg lactate 5 mmol three times a day; (b) tablets containing Mg citrate/Mg lactate and Mg hydroxide, 5 mmol three times a day; (c) tablets containing Mg hydroxide (Emgesan 10.3 mmol) twice a day; (d) solutions with Mg chloride (0.5 mmol/ml) 10 ml three times a day. There was no statistical difference in urine elimination after intake of the different preparations. The differences in Mg elimination/24 h discriminated between control and treatment groups just as well as or better than differences calculated on the basis of Mg/creatinine ratios.

Administration, Oral↗

The form of selenium determines the response to supplementation in a selenium replete population.

In an ongoing study of selenium bioavailability, effects of supplementation with organic and inorganic forms of selenium were investigated in healthy, Norwegian women, aged 23-50 years. In phase I of the study, 58 women received 200 micrograms selenium per day either as selenite or selenium-rich pea flour for 3 months. The selenium tablets were taken together with placebo or ascorbic acid in a double blind design. Initial blood and serum selenium concentrations were 153 +/- 15 micrograms/l and 117 +/- 12 micrograms/l, respectively. These are average values for Norwegians. Indications of increased blood levels were seen in all groups, but the rise reached significance only for the subgroup receiving selenite and ascorbic acid, 14 micrograms/l, P less than 0.05. On the other hand, selenium analysis of 72-h urine samples confirmed that at an average 50 per cent of the selenium supplements had been absorbed. In phase II of the study, 28 of the participants continued for another 5 weeks, still on 200 micrograms Se per day, but this time consuming commercially available preparations. Of four preparations that were tested, two consisted of yeast Se. Only one of these produced a significant rise in blood and serum selenium levels, 60 and 55 micrograms/l respectively. Blood glutathione peroxidase values were not affected by any supplementation. The study demonstrates that different forms of organic selenium elicit widely different responses when administered to a relatively selenium-replete population, and that the explanation for this must be sought at the metabolic level.

Adult↗