[A general practitioner's dilemma--an odyssey directed by changing winds of politics].
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Family Practice↗
Biomedical subjects
B Carlsson
Publications and source records attributed to B Carlsson.
Amiodarone is a dose-dependent noncompetitive and competitive inhibitor of T3 binding to thyroid hormone receptor subtype beta 1, whereas disopyramide, lignocaine, propafenone, metoprolol, dl-sotalol, and verapamil have no inhibitory effect.
The cardiovascular and electrophysiological effects of amiodarone resemble those of hypothyroidism. The drug has a structural resemblance to thyroid hormone (T3). Previous studies indicate that amiodarone exerts its major effect through antagonism of T3, probably as a result of inhibition of ligand binding to the thyroid hormone receptor (ThR). There are five subtypes of ThR, of which the beta 1 is the most prominent in the human heart. Our first aim was to investigate whether ThR is involved in a general antiarrhythmic mechanism for antiarrhythmic drugs or whether this action is specific for amiodarone. Therefore, we studied the affinity of one antiarrhythmic drug from every Vaughan-Williams group on T3 binding to human ThR beta 1 (hThR beta 1). Second, we wished to investigate whether amiodarone is a competitive or noncompetitive inhibitor. hThR beta 1, expressed in insect cells using a recombinant baculovirus, was used in regular binding competition assays. Disopyramide, lignocaine, propafenone, metoprolol, dl-sotalol, and verapamil had no effect on T3 binding to hThR beta 1. Amiodarone showed a noncompetitive binding pattern at low concentrations (0.25-2 microM) and a competitive binding at high concentrations (2-8 microM). Among the antiarrhythmics tested, only amiodarone had affinity for hThR beta 1. This may represent a novel type of antiarrhythmic mechanism. The finding that amiodarone, in concentrations corresponding to therapeutic range in plasma, shifts from a noncompetitive to a competitive inhibitor, is of clinical interest in comparisons of low- and high-dose treatment.
Amiodarone↗
Aberrations in titer and avidity of serum IgM and IgG antibodies to microbial and food antigens in IgA deficiency.
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Antibody Affinity↗
Chronic elevation of cAMP levels induces changes in the adenylate cyclase system, opiate receptor sensitivity and levels of Gs-mRNA in cultured neurons.
Neurons in primary culture were treated (5 days) with the adenylate cyclase stimulator 10(-5) M forskolin. The basal adenylate cyclase was decreased by 57%. The acute stimulatory effect of forskolin was down-regulated by 48%. The inhibitory effects of the 3 opiate receptor agonists (mu, delta and kappa) were partly abolished. The abundance of mRNA encoding the stimulatory G-protein (Gs) was decreased prominently. The data indicate that the cAMP system in neuronal cells in primary culture is under dynamic regulation, possibly including altered Gs-protein gene expression. Furthermore, long-term forskolin treatment might induce increased proliferation in susceptible neural blast cells.
Adenylyl Cyclases↗
Distribution of IGF-I mRNA and IGF-I binding sites in the rat kidney.
In the present study we have investigated the distribution of IGF-I mRNA and IGF-I binding sites in the rat kidney. The distribution of IGF-I mRNA was investigated using a simple and sensitive non-radioactive in situ hybridisation technique based on probe labelling with digoxigenin labelled-UTP followed by detection with conventional immunocytochemical techniques. IGF-I mRNA was found predominantly in medullary collecting ducts and sparsely in cortical collecting duct cells. In addition IGF-I mRNA was expressed in scattered proximal tubular cells in the cortex and in cells confined to the glomerular tuft. IGF-I binding sites were studied using radiolabelled IGF-I and conventional autoradiographical techniques on tissue sections. It was found that IGF-I binding sites were widely distributed throughout the entire kidney and that the specific binding was highest in the inner medulla. These findings add further complexity to the understanding of IGF-I production and action on renal structures.
Animals↗
Altered amounts of G-protein mRNA and cAMP accumulation after long-term opioid receptor stimulation of neurons in primary culture from the rat cerebral cortex.
Primary neuronal enriched cultures were incubated with mu (morphine, 10(-5) M), delta (DPDPE, 10(-6) M) and kappa (U-50,488H, 10(-5) M) receptor agonists for 5 days, respectively. Thereafter the acute inhibitory actions of mu, delta or kappa receptor agonists on forskolin stimulated cAMP accumulation was assayed. The effect of long term opioid treatment on the steady-state level of G-protein mRNA (G alpha s, G alpha i-1 and G alpha i-2) was analyzed using an RNAase protection hybridization assay. Incubation for 5 days with kappa receptor agonist resulted in an attenuated ability to decrease the accumulation of cAMP by kappa receptors, as well as mu and delta receptors, which was also observed after 5 days of incubation with the delta receptor agonist. Furthermore, the adenylate cyclase responsiveness to forskolin stimulation was markedly reduced in cultures treated with either delta or kappa receptor agonists. Five days of incubation with kappa receptor agonist resulted in an increase in the levels of G alpha s and G alpha i-2 mRNAs. No effects on the amounts of G alpha s mRNA, G alpha i-1 mRNA or G alpha i-2 mRNA were detected after 5 days of delta receptor stimulation. On the other hand, 5 days of mu receptor stimulation decreased the amounts of G alpha s, G alpha i-1 and G alpha i-2 mRNA. Incubation with kappa receptor agonist for 24 h resulted in a significant decrease in the forskolin-stimulated accumulation of cAMP. The stimulatory effect of forskolin was further decreased after 3 days incubation with kappa receptor agonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Regulation of G-PROTEIN mRNA abundancy and cAMP accumulation after long-term opioid incubation in primary cultures of astroglia from the rat cerebral cortex.
Primary astroglial cultures were incubated with delta (10(-6) M DPDPE) or kappa (10(-5) M U-50,488H) receptor agonists for 5 days. Thereafter, the acute inhibitory actions of delta or kappa receptor agonists on forskolin stimulated cAMP accumulation were assayed. The G alpha s, G alpha i-1 and G alpha i-2 mRNA levels were quantified after 5 days of either delta or kappa receptor agonist treatment using a solution hybridization, RNase protection assay. Pronounced effects were observed after 5 days of kappa receptor agonist [10(-5) M U-50,488H] incubation. This treatment resulted in an attenuation in the acute inhibitory action of delta and kappa receptor agonists. Furthermore, a decreased stimulatory action of forskolin was seen. Similar effects were also seen after delta receptor stimulation. We also investigated the effects after 24 h and 3 days of incubation with the kappa receptor agonist (10(-5) M) U-50,488H. The 24 h incubation resulted in a decreased sensitivity to the acute inhibitory action of delta and kappa receptor agonists in the astroglial cultures. This effect was further accentuated after the 3 days of incubation with 10(-5) M U-50,488H. No significant change was seen in the basal accumulation of cAMP after incubation with the kappa agonist U-50,488H. However, after 5 days of incubation with the delta agonist DPDPE, a significantly increased basal accumulation of cAMP was seen in the astroglial cultures. After 5 days of delta or kappa agonist incubation, an increase in G alpha s mRNA level and a decrease in G alpha i-2 mRNA level was seen compared with controls. No statistically significant alterations in the amount of G alpha i-1 mRNA were seen. The data obtained in the present study indicate that the effects of long-term opioid treatment alters the sensitivity of glial cell opioid receptors. Furthermore, long term opioid treatment induces alterations in glial G-protein mRNA levels.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
High frequency of mammary adenocarcinomas in metallothionein promoter-human growth hormone transgenic mice created from two different strains of mice.
Transgenic mice were developed by injecting a mouse metallothionein promoter-human growth hormone (Mt-hGH) gene fragment into the pronucleus of C57Bl x DBA/2J-f2 or C57Bl x CBA-f2 one cell embryos. Six founder animals with the C57Bl x DBA genetic background grew 1.3-2.2 times larger than littermate controls and had higher levels of hGH in plasma (4.6-279 mU/l). Three of the four female transgenic founders developed malignant papillar adenocarcinomas of mammary origin at 27-43 weeks of age. One male transgenic founder was successfully mated and two of three female transgenic offsprings developed mammary tumors. To examine if the tumor induction was dependent on the strain of mice used the experiments were repeated using animals with different genetic background. Fourteen female hGH transgenic mice from five founder animals were generated using C57Bl x CBA-f2 mice. Thirteen of the animals had elevated levels of hGH in plasma (7-1960 mU/l) and grew larger than control animals. Nine of the animals developed mammary adenocarcinomas. Four of the hGH expressing animals did not demonstrate macroscopic tumor formation but have not yet been analyzed histologically. The present study suggests that markedly elevated endogenous levels of GH cause mammary carcinoma in hGH transgenic mice. The present animal model might prove useful for studying molecular mechanisms involved in the development of hormonally induced mammary tumors.
Adenocarcinoma, Papillary↗
Acute myocardial infarction patients' chest pain as monitored and evaluated by ambulance personnel.
A delicate duty for ambulance personnel is to care for patients who suffer from chest pain, caused by acute myocardial infarction (AMI-patient). In Sweden pain-relieving drugs may be administered, such as: oxygen, entonox, or morphine according to the skill of the ambulance personnel. The aim of this study was to find out if AMI-patients' expressions of pain were monitored and evaluated, in which way the AMI-patients received pain-relief, and to which degree they were relieved of pain. Examinations of the records of the ambulance personnel's observations during transport of AMI-patients revealed that nine tenths of those who complained about chest pain received pain-relieving drugs. The results of the treatments varied, however, from a good rate of response to morphine to less responses to oxygen and entonox. In order to treat AMI-patients who are in need of pain-relief during their transit to hospital the ambulance personnel must possess thorough knowledge of both pain theory and communication theory. Furthermore, they need tools for assessment of pain and for administering adequate pain-relieving drugs in clinical practice. In the future it may be necessary to differentiate between ambulance personnel in routine service and those in emergency service according to their levels of education.
Allied Health Personnel↗
Expression of functional growth hormone receptors in human granulosa cells.
Both clinical and experimental evidence suggest that growth hormone may be of importance for ovarian function. The present study investigated whether growth hormone receptors are expressed in human granulosa cells. Granulosa cells were isolated either from natural cycles or from stimulated cycles in the course of in-vitro fertilization. Total RNA hybridized with a 32P-labelled rat growth hormone receptor cRNA probe revealed one major transcript with an estimated size of 4.5 kb and one minor transcript with an estimated size of 1.3 kb. Biotinylated growth hormone was used to analyse growth hormone binding. Competitive growth hormone binding was detected in freshly isolated granulosa cells, as well as in cultured cells. Growth hormone augmented basal and/or follicle stimulating hormone-stimulated steroidogenesis in granulosa cells obtained from patients with natural cycles, but the response to growth hormone stimulation showed considerable variation. We conclude that functional growth hormone receptors are present in human granulosa cells and that growth hormone, therefore, may have an important role in ovarian function.
Analysis of Variance↗
The urgency of care need and patient satisfaction at a hospital emergency department.
Satisfaction with the treatment and service at a hospital emergency department (ED) in a Swedish suburban area was generally high according to a questionnaire carried out among 758 patients with a 75 percent response rate. Satisfaction with the ED, however, was significantly lower among patients who were triaged nonurgent than among the immediate and urgent triage patients. This was especially true for younger patients.
Aged↗
Oral ketoconazole prophylaxis for Candida infections during induction therapy for acute leukaemia in adults: more bacteraemias.
We determined whether ketoconazole prophylaxis might reduce Candida colonization and infections in adult patients with acute leukaemia. During first-remission induction therapy 50 patients were treated with 200 mg ketoconazole administered orally daily, while 57 patients received placebo in a double-blind, randomized trial. The duration of severe neutropenia (granulocytes less than 0.1 x 10(9) l-1) represented 36% of the study period in the ketoconazole group and 26% in the placebo group (P = 0.043). Although fewer patients presented with positive Candida surveillance cultures and serological evidence of Candida infection in the ketoconazole group compared to the placebo group, two candidaemias and one Trichosporum fungaemia were observed in the ketoconazole group. Moreover, significantly more bacteraemias were noted in the ketoconazole group (n = 37) than in the placebo group (n = 21) (P = 0.004). Thus, although oral ketoconazole prophylaxis might be associated with less Candida colonization and fewer seroconversions, it also resulted in more bacteraemias and longer duration of severe neutropenia, suggesting that caution should be exercised when ketoconazole (or related drugs) is given to this group of immunocompromised hosts.
Antineoplastic Combined Chemotherapy Protocols↗
Aberrations in titre and avidity of serum IgM and IgG antibodies to microbial and food antigens in IgA deficiency.
The antibody levels and relative avidity of serum IgM and IgG antibodies against E. coli O antigens, poliovirus type 1 and beta-lactoglobulin were determined with enzyme-linked immunosorbent techniques in IgA deficient (IgAd) patients with frequent respiratory tract infections and healthy IgAd individuals. Healthy individuals with normal immunoglobulin levels served as controls. The IgM antibody levels against the bacterial, viral and food antigens and the IgG antibody levels against the bacterial antigens were significantly higher in the IgAd group with recurrent infections than in the group of healthy IgAd individuals. The symptomatic IgAd group had significantly higher levels of the IgG antibodies against the bacterial antigen, also when compared with controls. In contrast the healthy IgAd individuals had the highest avidities of IgM antibodies to the viral and food antigens. The high avidities of antibodies could be a compensatory host defence mechanism in IgAd. These aberrations may appear as a consequence of increased mucosal exposure in IgAd to antigens such as E. coli or beta-lactoglobulin, but presumably not to poliovirus which is only exceptionally present in the milieux. They could also be a result of the previously suggested dysregulation of antibody responses in IgAd.
Antibody Affinity↗
A comparison of secretory antibodies in breast-fed and formula-fed infants over the first six months of life.
In the present study salivary IgA, anti-Escherichia coli, anti-beta-lactoglobulin and anti-poliovirus type 1 IgA and IgM in serum and saliva were evaluated longitudinally in 13 breast-fed and 14 formula-fed infants over the first six months of life. Salivary IgA was quantified by electroimmunodiffusion; specific IgA and IgM antibodies were determined in serum and saliva by ELISA. Salivary IgA was significantly lower at age one month in breast-fed compared with formula-fed infants but in breast-fed infants salivary IgA increased with age and was significantly higher at six months than at one month. In both groups of infants, at the age of six months, salivary IgA levels were significantly lower than in adult controls. No significant differences in secretory anti-E. coli were observed between the two groups of infants. Salivary anti-poliovirus IgA and IgM antibodies increased transiently only to disappear in most babies at age six months, while anti-beta lactoglobulin IgA and IgM, present in saliva at all ages, showed a wide scatter. No important differences in specific serum IgA or IgM antibodies were observed either between the groups or at different times within the groups.
Age Factors↗
Presence of non-maternal antibodies in newborns of mothers with antibody deficiencies.
To explain the mechanism for induction and production of specific antibodies found in the newborn already at birth, without previous known exposure to the antigen, we chose a model that presumably excluded the possibility of specific antibodies being transferred from the mother to the fetus. Specific IgG, IgA, and IgM antibodies against Escherichia coli and poliovirus antigens were determined with ELISA in serum, saliva, and amniotic fluid from hypogammaglobulinemic and IgA-deficient mothers as well as in cord serum, saliva, and meconium from their offspring. All the mothers lacked IgA and some also lacked IgM antibodies, which were found in their healthy newborns. The amniotic fluid from a hypogammaglobulinemic mother lacking IgA contained small amounts of IgA antibodies, which were also found in the neonate, suggesting a fetal origin. There was evidence for the presence of antiidiotypic antibodies to poliovirus in the cord sera. We propose that idiotypic and/or antiidiotypic IgG antibodies transferred via the placenta from the mother to the fetus can initiate specific immune responses seen in the newborn. Thus, it may be that transplacental IgG not only passively protects the newborn, but also actively primes the fetus during fetal life via its content of idiotypic and/or antiidiotypic antibodies.
Agammaglobulinemia↗
Maternal cigarette smoking, breast-feeding, and respiratory tract infections in infancy. A population-based cohort study.
This population-based study comprised 192 mothers and their infants; 58 mothers were smokers and 134 non-smokers. At the 18-month infant check-up at the child health clinic, mothers were questioned about the length of the breast-feeding period, both exclusively breast-feeding and overall breast-feeding time. The numbers of antibiotic-treated respiratory tract infections (RTIs) during the first year of life were noted during a scrutiny of records at the district physician's surgery and child health clinic of the Health Centre, and at the paediatric and ENT departments of the Central Hospital. We were unable to find any connection between the duration of breast-feeding and the number of antibiotic-treated RTIs in the infants. This applied to both exclusively breast-feeding period and overall breast-feeding period. Further, it was shown that infants of smokers were affected by RTIs more often than those of non-smokers, the incidence figures being 1.16 vs. 0.76 antibiotic courses per infant and year, respectively. Moreover, infants of smokers were breast-fed for a shorter period than those of non-smokers, the mean values being 3.3 vs. 4.3 months, respectively, for the period of exclusively breast-feeding, and 5.0 vs. 7.2 months, respectively, for the overall breast-feeding period.
Adult↗
[Emergency departments are more popular among elderly patients than among young ones].
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Adult↗
Interaction of P-fimbriated Escherichia coli with human meconium.
The ability of Escherichia coli with different receptor specificities to interact with meconium was studied. E. coli strains expressing P-fimbriae, specific for Gal alpha 1-4Gal beta-containing receptors, were agglutinated by meconium at high titres. This reaction was inhibited by globotetraosylceramide. The attachment of P-fimbriated E. coli to human colonic epithelial cells of the HT-29 cell line was inhibited by meconium. Some type 1 fimbriated strains were agglutinated by meconium, but the agglutination was rarely blocked by methyl alpha-D-mannoside. The attachment by type 1 fimbriated strains to HT-29 cells was reduced by meconium only in some cases. These results suggest that meconium interacts with the P-fimbriae of E. coli, in a way that may influence bacterial colonization of the neonatal intestine.
Adhesins, Escherichia coli↗