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Biomedical subjects

B Holstein

Publications and source records attributed to B Holstein.

At least 19 recordsLinked to original sources

Socioeconomic health inequalities among a nationally representative sample of Danish adolescents: the role of different types of social relations.

STUDY OBJECTIVE: To investigate the role of different types of social relations in adolescent health inequalities. DESIGN: Cross sectional study. Measures included family social class, indices of social relations to parents, friends, teachers, and school. SETTING: Random sample of 55 schools in Denmark. PARTICIPANTS: Nationally representative sample of 5205 students from grades 5, 7, and 9. MAIN OUTCOME MEASURES: Self reported physical and psychological symptoms. RESULTS: Adolescents from families of lower socioeconomic position reported more physical and psychological symptoms. This ranged from 40% increased odds for multiple physical symptoms among less advantaged girls, to 90% increased odds of multiple psychological symptoms for less advantaged boys. Relationships with friends or teachers showed small social class differences, while strong and consistent social class differences were found in the ways adolescents reported their own and their parents relations to school. For example, girls from families of lower socioeconomic position were more than four times as likely to report their parents unwilling to attend school meetings (odds ratio=4.54, 95% confidence intervals: 2.68 to 7.69). Poorer relations with parents, peers, teachers, and school were all associated with worse health. Patterns of parent-child relations with the school were the greatest contributors to socioeconomic differences in physical and psychological symptoms. CONCLUSIONS: The school is one of the first important social institutions directly experienced by children and socioeconomic differences in how adolescents and their parents relate to the school may be part of the cascade of early life influences that can lead to later social and health disadvantage.

Adolescent↗

Pharmacodynamic modelling of reversible gastric acid pump inhibition in dog and man.

H 335/25, a 4-amino quinoline, belongs to a new class of reversible gastric acid pump inhibitors. A potential advantage of such drugs over the irreversible proton pump inhibitors (PPIs) is better control over the effect-time profile. Dose escalation studies were performed to characterize the effect on acid secretion in dogs (n=24) and healthy male subjects (n=12). The effect-time profile was delayed compared to the concentration-time profile. A model-based approach, using non-linear mixed effects modelling, was applied to quantify and elucidate the mechanism for the delayed effect. Three different models were investigated: (1) a slow equilibration preceding the formation of drug-enzyme complex, modelled by an effect-compartment, (2) a slow equilibration between free drug, free enzyme and drug-enzyme complex, described by a kinetic binding model, and (3) a delay between enzyme inhibition and the measured response, described by an indirect response model. Model 2 was shown to be superior to models 1 and 3, for both dog and human data. The dissociation rate constant, k(off), was estimated to be 0.85 and 0.88 h and the calculated equilibration constant, K(d), was 160 and 250 nM in dog and man, respectively. Simulations of the predicted time-course of the effect beyond the 4-5-h observation period was similar for the three models.

Administration, Oral↗

Socioeconomic position and smoking behaviour in Danish adults.

AIMS: The associations between smoking and various socioeconomic indicators may have different implications and causes, which may also vary according to sex and birth cohort. This study analyses how two dimensions of socioeconomic position, an individual (education) and a structural (occupation) indicator, are associated with ever, current and ex-smoking. METHODS: Data on smoking behaviour were collected in five cross-sectional surveys of random samples of the general Danish population aged 20 years or more at intervals between 1982 and 1994. In total, 8,054 men and 8,281 women participated. Logistic regression was used to analyse the influence of education and occupation on smoking behaviour controlling for sex and birth cohort. RESULTS: In cohorts born after 1930 ever and current smoking were related to years of school education and current occupation. The prevalences of ever and current smoking were highest among the least educated, unskilled workers, unemployed persons and persons who received welfare benefits. A significant interaction between birth cohort and education indicated that the educational difference in ever and current smoking increased significantly with increasing year of birth. In multivariate analysis controlling for sex and birth cohort, ex-smoking seemed to be more strongly associated with education than occupation. Those with 12 or more years of school education had twice as high a chance of being ex-smokers as those with 7 years of school or less. CONCLUSION: Smoking behaviour is strongly associated with both individual and structural indicators of socioeconomic position in Danish adults in all cohorts except for those born before 1930.

Adult↗

Social relations: network, support and relational strain.

We introduce a conceptual framework with social relations as the main concept and the structure and the function of social relations as subconcepts. The structure of social relations covers aspects of formal relations and social network. The function of social relations covers social support, social anchorage and relational strain. We use this conceptual framework to describe social relations in the Danish population, with questionnaire data from the Danish Longitudinal Health Behaviour Study including a random sample of each of the age groups 25-, 50-, 60-and 70-year olds, N = 2,011. The postal questionnaires were answered by a random sample in each of the age groups. The results show marked age and gender differences in both the structure and the function of social relations. The social network, measured as weekly contacts, weakens with age and so does instrumental support. Emotional support is unrelated to this decline in contact frequency and appears to be at the same level for younger and older individuals. Relational strain, measured as conflicts, declines with age for all kinds of social relations. The weakening of the social network with age does not seem to affect the level of emotional support and in turn seems to be partly compensated for by a simultaneous decline in relational strain.

Adult↗

A multicenter questionnaire investigation of attitudes toward hand hygiene, assessed by the staff in fifteen hospitals in Denmark and Norway.

A questionnaire survey was carried out anonymously among 2557 health care workers in Denmark and Norway to identify and quantify factors that affect the handwashing behavior of physicians, nurses, and other staff groups who perform direct patient care. For number of daily patient contacts physicians reported significantly fewer instances of hand hygiene (HH) per day than did those in other medical professions. Male physicians reported significantly fewer HH per day than did their female colleagues. Significant differences were found among staff groups in emphasis on factors motivating and discouraging HH. The main motivating factor for all groups, however, was an awareness that HH is important for the prevention of infection. Skin problems from frequent handwashing and the use of agents that irritate and dry the skin were the main reasons for disinclination toward HH. The number of points given to these statements correlated well with the stated frequency of HH in staff groups with relatively many (9 to 24) patient contacts per day. Many studies have revealed low standards of HH in health care settings. Whenever HH is taught, the significance of HH for the prevention of infection is always stressed. The participants in this survey were well aware of this significance, but there is still a discrepancy between theory and practice. Goal-specific strategies to improve HH practices would probably be more effective if more were done to minimize the factors that health care workers find detrimental to HH. Continual evaluation of the possibly detrimental effects of current hand washing agents should also be carried out.

Attitude of Health Personnel↗

Effect of somatostatin on basal and stimulated gastric secretion in the cod, Gadus morhua.

In vivo secretion of gastric acid and pepsin has been studied in pylorus-ligated cod. Basal acid output amounted to 100-150 mumol H+.kg-1.h-1 and pepsin secretion to 1 mg.kg-1.h-1. In response to bombesin nonapeptide (2.4 nmol.kg-1.h-1) and histamine (81 nmol.kg-1.h-1), acid secretion increased to approximately 200 and 600% of the basal level, respectively. Pepsin output was marginally affected by histamine but increased to approximately 3 and 15 times the basal level during treatment with bombesin and eledoisin (3.27 nmol.kg-1.h-1). Somatostatin (SS-14, 15 nmol.kg-1.h-1) inhibited basal acid secretion by 85%. It also inhibited the acid secretion during stimulation with bombesin (68%) and histamine (57%), but although the former effect could be explained by removal of the basal component, the latter could not. Basal pepsin secretion was not affected by SS-14. A slight inhibition (28%) of the peak pepsin response to eledoisin was demonstrated, and bombesin failed to stimulate pepsin secretion during treatment with SS-14. These results indicate that endogenous somatostatin, if present in the cod stomach, could play a role in the regulation of gastric secretion.

Animals↗

Gastrin/CCK-like immunoreactivity in endocrine cells and nerves in the gastrointestinal tract of the cod, Gadus morhua, and the effect of peptides of the gastrin/CCK family on cod gastrointestinal smooth muscle.

Immunohistochemistry shows the presence of one or several gastrin/cholecystokinin (CCK)-like peptides in the gastrointestinal tract of the Atlantic cod, Gadus morhua. Immunoreactive (IR) endocrine cells are present mainly in the lower part of the cardiac and in the pyloric stomach, with a concentration to the inner curvature, and in the proximal part of the intestine, especially in the area of the pyloric caeca, after which the population density of IR cells decreases anally. IR nerve fibers are found in the myenteric plexus and muscle layers of the stomach only. Radioimmunoassays, performed with two C-terminal specific gastrin/CCK antisera, confirm the immunohistochemical findings. The highest levels of IR material are found in the mucosa of the pyloric caeca, the proximal intestine, and the pyloric part of the stomach. The smooth muscle layers contain IR material in a decreasing gradient toward the rectum. The excitatory effect of gastrin/CCK-related peptides on gut smooth muscle is investigated in isolated strip preparations of the gut wall. Of the peptides tested, cerulein is the most potent, followed by CCK 8 and gastrin 17, while gastrin 5 is the least effective. Sulphated CCK 8 gives a higher amplitude of the response but in the same concentration range as nonsulphated CCK 8. It is concluded that one or several gastrin/CCK-like peptides are present in the gut of the cod and may be involved in the nervous and endocrine control of the cod gut motility.

Animals↗

Characterization with agonists of the histamine receptors mediating stimulation of gastric acid secretion in the Atlantic cod, Gadus morhua.

Gastric acid secretion in response to a number of agonists, active at H1 and/or H2-receptors, were measured in the gastrically and intestinally perfused cod. Histamine (D50 = 15 nmol/kg X h) was the most potent of the agonists tested. The H2-active agonists 4-methylhistamine (4-MeHi), Na-MeHi, and Na,Na-MeHi were about 25 times less potent than histamine in this in vivo model. Na,Na-MeHi was a partial agonist, while 4-MeHi and Na-MeHi elicited maximum responses similar to that of histamine. Dimaprit and impromidine, two highly selective H2-agonists, failed to stimulate acid secretion under basal conditions, and inhibited histamine-stimulated acid secretion. The H1-selective 2-MeHi and 2-pyridylethylamine (2-PEA) were essentially inactive. It is concluded that the cod gastric histamine receptor related to acid secretion is of the H2-class. It is not, however, identical to the mammalian gastric H2-receptor, and should be placed in a separate subgroup.

Animals↗

Effects of tachykinins on gastric acid and pepsin secretion and on gastric outflow in the Atlantic cod, Gadus morhua.

Gastric acid and pepsin responses to substance P, physalaemin, eledoisin, and an eledoisin-related peptide, [Lys6]eledoisin-(6-11), were measured in gastrically and intestinally perfused cods. The intestinal perfusion maintains water balance and inhibits drinking. During basal conditions acid secretion was stimulated (approximately equal to 25%) by low doses (less than 0.13 nmol X kg-1 X h-1) of physalaemin and eledoisin. High doses (greater than 16 nmol X kg-1 X h-1) were inhibitory. Median and very high doses of substance P and eledoisin-related peptide, respectively, tended to stimulate acid secretion. All tachykinins were extremely efficacious pepsigogues. Physalaemin and eledoisin were the most potent (D50 approximately 10(-10) mol X kg-1 X h-1) but produced fading and submaximal responses at high doses. The fading persisted despite endogenous acidification produced by histamine stimulation. Relative to physalaemin, the potencies of substance P and eledoisin-related peptide were 0.04 and 0.001. The results suggest that some tachykinin may be a physiological stimulator of pepsin secretion and that the effect on acid secretion results from activation of both stimulatory and inhibitory pathways. The inhibitory component probably includes a cholinergic link. Gastric volume outflow increased during infusion of physalaemin, eledoisin, and (slightly) substance P. The response, which was not related to acid secretory rate (and conceivably not to volume secretion), suggests that a tachykinin may be involved also in the regulation of drinking.

Acid-Base Equilibrium↗

Effect of 5-HT on basal and stimulated secretions of acid and pepsin and on gastric volume outflow in the in vivo gastrically and intestinally perfused cod, Gadus morhua.

Gastric acid and pepsin responses to 5-HT was measured, in cod, during gastric and intestinal perfusions. During basal conditions, both acid and pepsin secretions were stimulated by 0.25 mumol/kg X h of 5-HT. A higher dose, 1 mumol/kg X h inhibited acid secretion and stimulated the output of pepsin both during basal conditions and during stimulation with histamine or carbachol. Histamine and carbachol, when given alone, were powerful acid stimulators but in comparison with 5-HT poor pepsigogues. Most probably due to inhibition of gastric volume secretion, gastric outflow volume decreased during treatment with higher doses of 5-HT. However, when the intestinal perfusion was omitted and water support instead given by the intramuscular route, 5-HT induced a large increase in gastric outflow volume. Our results suggest that 5-HT may be a physiological regulator of acid and pepsin secretion in the fish. The dipsogenic effect seen in the absence of intestinal perfusion indicates that 5-HT may be involved also in the regulation of drinking.

Aniline Compounds↗

Inhibition of gastric acid secretion inthe Atlantic cod, Gadus morhua, by sulphated and desulphated gastrin, caerulein, and CCK-octapeptide.

Gastric acid secretory effects of gastrin/CCK-like peptides have been assayed in cods rendered "spontaneously" secreting by a continuous intestinal perfusion with diluted (33%) seawater. A high dose of pentagastrin induced a weak stimulation (31%) of acid output, while gastrin 17-II, caerulein and CCK8 were inhibitory. Caerulein was the most potent peptide, with an estimated D50 for inhibition of 0.013 nmol/kg.h. Although displaying lower potencies, also the desulphated forms of gastrin-17, caerulein and CCK8 were inhibitory. The results may be explained by release of an endogenous inhibitor, or by interaction with endogenous "codfish gastrin". In the latter case two alternatives are considered: Either gastrin 17, CCK8, and caerulein possess lower efficacies than "codfish gastrin" and therefore act as partial agonists. Alternatively, "codfish gastrin" is itself an inhibitory principle (gastron), the effect of which is mimicked by gastrin 17, caerulein and CCK8. The actions of gastrin and the gastrin-like peptides in the cod indicate a structure-activity relationship different from previously described systems, both mammalian and submammalian.

Animals↗

Inhibition of gastric acid secretion by intestinal and parenteral administration of a mixture of L-amino acids in the Atlantic cod, Gadus morhua.

The effect on basal gastric acid secretion in the cod of a mixture of L-amino acids (AA) was studied. Acid secretion was measured during a 5 h treatment period when the AA was administered intestinally, i.m. or i.v., and plasma alpha-amino nitrogen following the treatment period. Acid secretion was inhibited, the depression related to the plasma level of AA but unrelated to the administration route. It is suggested that acid secretion is inhibited by absorbed AA acting from the blood side, without involvement of an intestinal mechanism.

Amino Acids↗

Effects of exogenous angiotensin II in the Atlantic cod, Gadus morhua. Observations on gastric acid secretion, gastric sham drinking and gastric mucosal plasma flow (14C-aniline clearance).

Cods were equipped with cannulae for drainage of the stomach and for the separate perfusion of the stomach (pure seawater containing phenol red as a volume marker) and intestine (diluted seawater). Acidity of the gastric effluence was titrated, its volume calculated from the phenol red concentration. Gastric mucosal plasma flow (MPF) was estimated by gastric 14C-aniline clearance. I.m. injection of angiotensin II (AII) depressed basal acid secretion in a dose-dependent fashion. Also the MPF was reduced, but relatively less than the secretory depression. Therefore, the AII-induced secretory inhibition could not be explained by restrained mucosal blood flow. Perfusion of the intestine with diluted seawater, or a continuous i.m. infusion of 0.6% NaCl both rendered the fishes non-drinking. A high dose of AII (150 micrograms/kg . h) induced drinking in intestinally perfused cod while lower doses (15, 50 micrograms/kg . h) did not. In i.m. saline-injected cod, all three doses were dipsogenic. The results suggest that 0.6% saline infusion induces a permanent satiety and that intestinal perfusion in addition induces a preabsorptive satiety. The preabsorptive satiety appears more resistant to the dipsogenic action of AII than the permanent one.

Angiotensin II↗

Effect of vagotomy and glucose administration on gastric acid secretion in the Atlantic cod, Gadus morhua.

Cods were prepared for measurement of gastric acid secretion. Cannulae were implanted for drainage of the stomach and for separate perfusion of the stomach and intestine. Fishes, intestinally perfused with diluted sea-water (33% SW) exhibited high rates of acid secretion. This "basal" secretion was abolished (96% inhibition) by bilateral vagotomy. Perfusion of the stomach with isosmotic glucose (5.5%) diminished the amount of titratable acid in the gastric effluence, and induced oral ingestion of water. Only part of the decrease could be explained by neutralization by ingested sea-water. Perfusion of the intestine with 5.5% glucose, containing sea-water to raise the osmolality to that of 50% SW, depressed gastric acid secretion compared to 50% SW-perfused controls, without significantly affecting oral intake of water. I.m. administration of glucose, increasing plasma glucose to the same level as intraluminal administration, did not affect acid secretion or oral water ingestion. The study demonstrates the existence of a potential intestinal mechanism for inhibition of gastric acid secretion, and indicates that vagal activity is independent of the blood glucose level in the cod.

Animals↗

The ultrastructure of the gastric glands and its relation to induced secretory activity of cod, Gadus morhua (Day).

Light and electron microscopic studies have been performed on different parts of cod stomach. The studies have been concentrated on the gastric glands of the gastric mucosa. The glands consist of only one cell type. This cell contains an apically located, comprehensive tubular system as well as zymogen granules and therefore probably secretes both acid and zymogen. The high degree of development of certain organelles and their mutual localization shows a structural organization which appears suitable for an effective secretion. What appears to be intermediate organelle forms are common. When acid secretion is increased by continuous intramuscular infusion of histamine or of carbachol the most marked structural changes are increases in the size of the gland lumen and in the cell membrane facing the lumen. Histamine in particular causes the appearance of numerous long and slender cell processes in an enlarged gland lumen. When the acid secretion, increased by histamine, had reached a plateau, metiamide was infused. This histamine H2-receptor antagonist caused a decrease in acid secretion as well as in the size of the gland cell surface to values characteristic of untreated cod.

Animals↗

Stimulation of gastric acid secretion and suppression of VIP-like immunoreactivity by bombesin in the Atlantic codfish, Gadus morhua.

Cods were equipped with cannulae for drainage of the stomach and for separate perfusion of the stomach (pure sea-water) and intestine (diluted sea-water). Acidity and volume of gastric effluence were measured. Plasma immunoreactive gastrin and vasoactive intestinal polypeptide (VIP) were assayed in some experiments. The high rate of "basal" acid secretion was further elevated by i.m. administration of bombesin, but not by pentagastrin. Exogenous VIP inhibited acid secretion. Following 5 h of bombesin infusion, plasma gastrin-IR was unaffected while VIP-IR was depressed compared to saline-treated controls. The possibility that bombesin stimulates acid secretion by inhibiting VIP-release is discussed.

Animals↗