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Biomedical subjects

L Rasmussen

Publications and source records attributed to L Rasmussen.

At least 19 recordsLinked to original sources

Response to mannitol in asymptomatic subjects with airway hyper-responsiveness to methacholine.

BACKGROUND: Bronchial provocation using methacholine, a cholinergic agonist, causes airway narrowing directly by contraction of bronchial smooth muscle. While methacholine has a high sensitivity for identifying airway hyper-responsiveness (AHR), it does not have a high specificity to diagnose asthma and false-positive responses may be observed in non-asthmatics. Mannitol is an osmotic stimulus that acts indirectly to cause airway narrowing by release of endogenous bronchoconstricting mediators. OBJECTIVES: We tested the hypothesis that subjects with asymptomatic AHR to methacholine would not have AHR to mannitol. METHODS: Sixteen subjects with a methacholine PD(20) <8 micro mol were challenged with mannitol. A positive response to mannitol was defined as a 15% decline in forced expiratory volume in 1 s (FEV(1)) after <635 mg (PD(15)). Expired nitric oxide (eNO) and blood eosinophils were also measured. RESULTS: The GM PD(20) for methacholine was 2.25 micro mol [95% confidence interval (CI): 2.19-5.29], the mean eNO was 14.7 p.p.b. (CI: 10.1-19.4) and the eosinophil count was 0.20 x 10(-9)/L (CI: 0.14-0.27 x 10(-9)/L). Only one subject (a smoker, 10 pack-years, FEV(1) 76% pred, non-allergic rhinitis, normal eNO and eosinophil count) also had a mild positive response to mannitol (PD(15): 451 mg). CONCLUSIONS: The response to mannitol was within the normal range in asymptomatic subjects with AHR to methacholine. Further evidence on the responsiveness to mannitol compared with methacholine in a random population sample is required to elucidate whether mannitol is a more specific test for diagnosing asthma.

Adult↗

Severe intoxication after an intentional overdose of amlodipine.

Intoxication with 280 mg of amlodipine caused severe hypotension, third-degree heart block and hyperkalaemia in a 36-year-old female patient. The patient was initially treated with fluids, dopamine, calcium chloride, and epinephrine without effect. The patient was then given a bolus injection of insulin and glucose as a temporary mean to treat the hyperkalaemia. We observed a rise in blood pressure (BP) after insulin was given and the BP was subsequently responsive to epinephrine. A possible positive inotropic effect of insulin therapy in patients with calcium channel blocker intoxication is in accordance with previous findings. In conclusion, it is suggested that hyperinsulinaemia-euglycaemia therapy may be considered as a first-line therapy in calcium channel blocker intoxication.

Adult↗

Gastrointestinal malformations in Funen county, Denmark--epidemiology, associated malformations, surgery and mortality.

AIM: To report the epidemiology, associated malformations, morbidity and mortality for the first 5 years of life for infants with gastrointestinal malformations (GIM). METHODS: Population-based study using data from a registry of congenital malformations (Eurocat) and follow-up data from hospital records. The study included livebirths, fetal deaths with a gestational age of 20 weeks and older and induced abortions after prenatal diagnosis of malformations born during the period 1980 - 1993. RESULTS: A total of 109 infants/fetuses with 118 GIM were included in the study giving a prevalence of 15.3 (12.6 - 18.5) cases per 10 000 births. Anal atresia was present in seven of the 9 cases with more than one GIM. There were 38 cases (35 %) with associated malformations and/or karyotype anomalies. Thirty-two of the 90 live-born infants died during the first 5 years of life with the majority of deaths during the first week of life. Mortality was significantly increased for infants with associated malformations or karyotype anomalies compared to infants with isolated GIM (p < 0.01). An uneventful surgical course was reported for 74 % of the 58 survivors. CONCLUSIONS: The prognosis for infants with GIM is highly dependent on the presence of associated malformations or karyotype anomalies. Surgery for GIM can be performed with low mortality. Morbidity is high for a small group of infants, but the majority of survivors have an uncomplicated surgical course.

Anal Canal↗

Effects of inhaled plasminogen activator on the balance between coagulation and fibrinolysis in traumatized pigs.

A profibrinolytic state is normal in the alveoli, but this may change as a result of trauma, possibly leading to fibrin deposition, a characteristic of acute lung injury/acute respiratory distress syndrome. Therefore, the present study investigated in a double-blind, placebo-controlled manner the effect of severe trauma on the alveolar fibrinolytic/coagulation balance, and the effect here-upon of inhalation of single-chain urokinase plasminogen activator (scu-PA) in pigs. The study shows an increased concentration of scu-PA in the bronchoalveolar lavage fluid of the treated animals in association with an increased plasmin-dependent fibrinolytic activity without increased systemic fibrinolytic activity, the transient increase in the concentration of scu-PA in the plasma being minimal. In conclusion, the study shows that activatable scu-PA can be nebulized to the lower respiratory tract and can increase the alveolar fibrinolysis without any significant systemic effects.

Administration, Inhalation↗

Cell death in Tetrahymena thermophila: new observations on culture conditions.

We previously suggested that the cell fate of the protozoan ciliate, Tetrahymena thermophila, effectively relates to a quorum-sensing mechanism where cell-released factors support cell survival and proliferation. The cells have to be present above a critical initial density in a chemically defined nutrient medium in order to release a sufficient level of these factors to allow a new colony to flourish. At a relatively high rate of metabolism and/or macromolecular synthesis and below this critical density, cells began to die abruptly within 30 min of inoculation, and this death took the form of an explosive disintegration lasting less than 50 milliseconds. The cells died at any location in the culture, and the frequency of cell death was always lower in well-filled vials than those with medium/air interface. Cell death was inhibited by the addition of Actinomycin D or through modifications of the culture conditions either by reducing the oxygen tension or by decreasing the temperature of the growth medium. In addition, plastic caps in well-filled vials release substances, which promote cell survival. The fate of low-density cultures is related to certain 'physical' conditions, in addition to the availability of oxygen within closed culture systems.

Animals↗

Genetics of resistance against defences of the host plant Barbarea vulgaris in a Danish flea beetle population.

One essential aspect of the study of the evolution of host-plant use by insects is (variation in) its genetic basis. The genetic basis of the ability of a flea beetle (Phyllotreta nemorum) to use the crucifer Barbarea vulgaris ssp. arcuata (G type) as a host plant was studied in a Danish population (Kvaerkeby) occurring naturally on this atypical host plant. Evidence was found that this ability was determined by a single, major, autosomal gene, although the presence of genes at additional loci at lower frequencies could not be excluded. No evidence was found for sex-linked inheritance, which was common in a second population in Denmark (Ejby) using Barbarea as a host plant. All beetles in the Kvaerkeby sample were homozygous 'resistant' to Barbarea defence. After crossing resistant F1 offspring from pairs consisting of a field-collected beetle and a susceptible one amongst each other, genotyping the F2 (reared on radish) showed a 1:2:1 ratio of homozygous resistant, heterozygous and susceptible beetles. No evidence was found for a reduction in the viability of beetles that were homozygous resistant at the autosomal locus, in contrast to what had been found earlier for two backcrossed lines founded by beetles from Ejby. The results show that there is variation in the genetic basis of host-plant use across local populations and imply that population structure should form part of the study of the interaction between P. nemorum and its host plants.

Animals↗

Phospholipase C and D in the commitment to survival or death in the early lag phase of tetrahymena cultures.

We made three kinds of experiments in order to elucidate aspects of physiological mechanisms involved in a series of specific events leading to either cell death or survival in the lag phase of culture growth. We studied the fate of newly inoculated Tetrahymena cells in small droplets at 'high' (more than 1000 cells ml(-1)) and 'low' cell densities (less than 600 cells ml(-1)) in a nutrionally complete, synthetic nutrient medium. Confirming previous results we found that the cells in high-density cultures multiplied to final densities around 500,000 cells ml(-1) and that cells in low-density cultures died before multiplying. The appearance of the cells was recorded with a video camera at 20 frames per second for 6 h or until they died. The results indicated that the death process took place within milliseconds. We also studied the effects of U 73122, an inhibitor of the phosphatidylinositol-specific phospholipase C, on cell survival at low densities. At low inhibitor concentrations low-density cells were rescued from dying. At high inhibitor concentrations all cells died, and phosphatidylinositol - but not phosphatidylserine and phosphatidylcholine - saved them. The results indicate that the paths leading to either cell death or to cell proliferation separate within the first few minutes after subcultivation into a new medium, since the first cells in each culture died within 4-30 min after inoculation. Our results also indicate that some PLC activity was required for stimulation of phospholipase D, and that cell death during the early lag phase is caused by a shortage in phosphatidylinositol before the phospholipase D activity is upregulated. These experiments are shedding light on the lethal consequences of a cellular depletion of the important signalling compound phosphatidylinositol in an in vivo system, and may help to elucidate mechanisms behind the century-old fact that eukaryote cells die when inoculated at too low a cell density to survive.

Animals↗

Human cytomegalovirus strains associated with congenital and perinatal infections.

The genotypes of human cytomegalovirus (HCMV) isolates from pediatric patients differs from those of infected adults in Australia. Genotypes were determined by PCR amplification of glycoprotein B (gB) sequences, with subsequent analysis by restriction fragment length polymorphism, single-stranded conformation polymorphism, heteroduplex mobility analysis and direct DNA sequencing. Restriction fragment length polymorphism analysis of gB showed genotypes gB1 (39%) and gB3 (30%) were more prevalent in infected children and two new genotypes (gB6 and gB7) were found. Single-stranded conformation polymorphism was used to group isolates into 22 further subtypes and suggested longitudinal co-infection or viral mutation was occurring over time. Heteroduplex mobility analysis was found to be the most accurate and concise of the four methods used for genotyping HCMV isolates. DNA sequencing was used to confirm the results obtained from heteroduplex mobility analysis, and identified two isolates that were incorrectly genotyped by restriction fragment length polymorphism analysis. Heteroduplex mobility analysis efficiently genotyped all samples and allowed estimation of sequence variation between isolates. These data suggest certain gB genotypes are associated more commonly with childhood infections, and these differ from strains associated with invasive disease in HIV patients.

Acquired Immunodeficiency Syndrome↗

Are cells rescued from 'low density death' by co-operation between phospholipases C AND D?

Cells of the ciliate Tetrahymena thermophila die when transferred at low density to a lipid-free nutritionally complete medium. This death is prevented and they will start to proliferate if protein kinase C is activated and this activation is sustained. We propose that this takes place in two stages. Firstly, the phospholipase C pathway beginning with and specific for phosphatidylinositol leads to the formation of diacylglycerol and inositol tris -phosphate. Diacylglycerol activates protein kinase C, and inositol tris -phosphate via Ca(2+)phospholipase D (PLD). Secondly, the protein kinase C response can now be sustained by diacylglycerol produced by phospholipase D, using phosphatidylcholine and phosphatidylserine as substrates. Should this switching from PI-specific phospholipase C (PLC) to phospholipase D fail, then the cell will die in the course of milliseconds during the minutes following inoculation.

Animals↗

Characterization of bone resorbing activity in gingival crevicular fluid from patients with periodontitis.

BACKGROUND: In attempts to elucidate factors stimulating bone resorption in patients with different inflammatory diseases in the vicinity of the skeleton, e.g., peridontal disease and rheumatoid arthritis, we are investigating the presence of bone-resorbing activity in a variety of inflammatory exudates. The aim of the present study was to characterize the bone-resorbing activity present in patients with periodontitis. METHODS: Bone-resorbing activity was assessed in gingival crevicular fluids (GCFs) collected from patients with periodontitis and from patients with no signs of gingivitis. Bone-resorbing activity was evaluated by analyzing the capacity of GCFs to stimulate the release of minerals and the breakdown of bone matrix proteins in cultured neonatal mouse calvariae. The concentrations of IL-1alpha, IL-1beta and PGE2 were determined with ELISA and RIA techniques, respectively. RESULTS: GCF eluates from 24 different healthy sites caused a 1.23+/-0.05 fold stimulation of 45Ca release, whereas GCF eluates from 45 different diseased (periodontitis) sites caused a 2.46+/-0.10 fold stimulation. The effect on 45Ca release was time- and concentration-dependent, inhibited by 3 different osteoclast inhibitors and associated with enhanced release of 3H from [3H]-proline-labelled bones. The activity in GCF causing enhanced 45Ca release was unaffected, or in some samples partially reduced, by ultrafiltration using a filter with a molecular weight cut-off of 3000 Daltons. The bone-resorbing activity was temperature sensitive (+90degrees C, 10 min). The concentrations of prostaglandin E2 (PGE2) in the diluted GCF eluates, used in the bone resorption bioassay, were too low to be responsible for the release of 45Ca. Antisera specifically neutralizing human IL-1a inhibited the stimulatory effect of GCF pooled from several diseased sites. The specific, recombinant human IL-1 receptor antagonist completely inhibited the effect of pooled GCFs. GCF eluates from diseased sites contained human IL-1alpha and IL-1beta at concentrations of 1838+/-294 pg/ml and 512+/-91 pg/ml, respectively. CONCLUSIONS: These data show that GCF contains activity(ies) stimulating osteoclastic bone resorption in vitro. The factor primarily responsible for this activity seems to be IL-1alpha, but IL-1alpha is not the sole activator of bone resorption in GCF.

Adult↗

[T validity of the diagnosis of urinary tract infection in children under two years of age].

In the Department of Paediatrics at Hillerød a valid diagnosis of urinary tract infection in children is defined to be at least 10.000 bacteria/ml. in two midstream specimens of urine or any bacterial growth in urine collected by a suprapubic aspiration or by bladder catheterisation. We decided to study if these criteria were fulfilled in our department, which takes care of urinary tract infections in children in the county of Frederiksborg with a catchment area of about 350.000 people. From 1994-1996 a total of 60 children younger than two years of age were treated for their first suspected urinary tract infection. The diagnosis was valid in 37% of the cases. Eighty-eight percent of the children received parenteral antibiotics for at least three days, and 86% were discharged with prophylactic antibiotics. All underwent urological ultrasonographic examination and 70% underwent an isotope micturition cystourethrography. Among patients with a valid diagnosis 68% were boys and 50% had urological abnormalities, whereas among patients without a valid diagnosis there were 33% boys (p < 0.025) and 24% had urological abnormalities (p = 0.0734). A valid diagnosis of a first urinary tract infection was established in 0.15% of children younger than two years of age in the county of Frederiksborg. This is lower than previously reported. The problem of false positive urinary tract infections thus may be important in general.

Age Factors↗

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Journal Article↗

Cholecystectomy in patients with normal gallbladder function did not alter characteristics in duodenal motility which was not correlated to size of bile acid pool.

Nine gallstone patients with normal gallbladder function as assessed by hepatobiliary scintigraphy were included. Fasting and postprandial duodenal motility were studied before and one month after an uncomplicated laparoscopic cholecystectomy. An ambulatory continuous pressure recording was obtained from 5 PM to 8 AM with a sampling frequency of 4 Hz. At 6 PM, the patients received a 1400-kJ standard meal. The size of the bile acid pool after cholecystectomy was measured according to the dilution principle using [C14]cholic acid as the marker. Preoperatively the migrating motor complex (MMC) cycle was 0.48/hr (quartiles 0.42-0.68) compared to 0.68/hr (0.43-0.77) postoperatively. This difference was not significant. An increase in the MMC cycle frequency was observed postoperatively in three patients, and a decrease was seen in four patients. The migration velocity was 5.61 cm/min (4.26-8.01) preoperatively and 7.16 cm/min (4.79-9.71) postoperatively, a difference that was not significant. The time period from meal ingestion to appearance of phase III was 297 min (218-431) at the preoperative examination and 443 min (192-494) at the postoperative examination. This difference was not significant. The size of the bile acid pool after cholecystectomy was 3.68 mmol (2.69-8.47) and was not significantly correlated to the frequency of the MMC cycle or the time period from food ingestion to phase III activity. It is concluded that in gallstone patients with a normally functioning gallbladder, cholecystectomy does not alter duodenal motility, which was not correlated to the size of the bile acid pool.

Adult↗

Molecular pathogenesis of human cytomegalovirus infection.

Despite progress in diagnosis and treatment of human cytomegalovirus (CMV) infection, we do not understand why, in hosts with comparable levels of immunosuppression, some CMV infections result in symptomatic CMV disease while others are limited to asymptomatic virus shedding with no discernible clinical consequences. CMV viral detection and quantification are useful for identifying those at highest risk, but do not consistently predict clinical outcome. Factors such as host genotype and immune response are active areas of research. However, the importance of CMV strain variability, recognized since 1976, is now receiving attention. Advances in technology that allow the rapid sequencing of viral DNA for purposes of strain characterization have fueled the renewed interest. The focus of this review will be to summarize our evolving knowledge of CMV strain variability and to document where possible a potential relationship to strain virulence. Studies with the UL55 (gB) envelope glycoprotein will be emphasized because of the ability to clearly identify naturally occurring variants, as well as the increasing number of reports that there are differences in biological activities that may contribute to virulence.

Cytomegalovirus↗

The effects of omeprazole on intragastric pH, intestinal motility, and gastric emptying rate.

BACKGROUND: The present study was designed to investigate whether omeprazole changes the characteristics and thereby the functions ascribed to fasting intestinal motility, postprandial motility, postprandial pH, and gastric emptying. METHODS: Ten healthy subjects were investigated. The studies were performed after 10 days of treatment with 40 mg omeprazole daily/placebo. Duodenal pressures and intragastric pH were detected by strain-gauge transducers and a pH electrode attached to a miniature computer. The meal consisted of an omelette labelled with 99mTc-sulphur colloids followed by 150 ml water labelled with 111In-diethylenetriamine pentaacetic acid. RESULTS: The difference in fasting intragastric pH between the two series was highly significant. The profile from the placebo series showed a relationship between phase activity and pH. The pH increased from phase I (median, 1.3; 95% confidence interval (CI), 0.9-1.6) to a maximum at 25% (1.8 (0.9-2.1)) and 50% (1.6 (1.1-3.8)) of cycle duration and decreased thereafter until the end of the cycle. The profile from the omeprazole series showed significantly higher values during the entire cycle but no relationship between phase activity and pH. Pretreatment with omeprazole was followed by a delay in gastric emptying of liquid at 30 min (64% (49%-66%) (omeprazole series) versus 78% (67%-83%); P < 0.01) and solid at 180 min (71% (48%-86%) (omeprazole series) versus 96% (87%-100%); P < 0.01). There was no significant difference in duration of postprandial motility (305 min (157-350 min) (omeprazole) versus 259 min (129-403 min)). CONCLUSIONS: Omeprazole eliminates the temporal relationship between intragastric pH and characteristics of the migrating motor complex and induces a delay in gastric emptying of both liquid and solid. A non-significant increase in duration of postprandial motility may represent a type-II error.

Adult↗

The variability of the incremental postprandial portal vein flow response is partly caused by a relationship between fasting flow rate and phase activity of the migrating motor complex.

OBJECTIVE: Results from studies on portal flow rate (PFR) have demonstrated a considerable intra- as well as interindividual variability of the incremental integrated response (IIR). We hypothesized that part of the variation of the IIR might be related to variability of the fasting PFR caused by a relationship between PFR and characteristics of the migrating motor complex (MMC). DESIGN: We examined 12 healthy men and PFR was recorded by using the percutaneous colour Doppler technique. Gastric emptying (GE) was determined by scintigraphy and the meal consisted of an omelette of 100 g (1400 kJ; 60% fat, 20% protein, 20% carbohydrates) tagged with 99mTc sulphur colloids followed by 150 ml water mixed with 111In DTPA. The design included recording of PFR in phase II as well as in phase III of the MMC. Meal ingestion took place in the following duodenal phase I. Postprandial recordings of GE and PFR were performed at 10 min intervals for the following 2 h. RESULTS: Median (95% confidence limits) amount of solid emptied at 120 min was 68% (59-81%). PFR in phase III was significantly higher than in phase II (1.56 l/min (1.35-1.93 l/min) vs 0.96 l/min (0.84-1.12 l/min), P< 0.001). PFR increased after the meal and a peak flow of 2.19 l/min (1.58-2.46 I/min) was recorded 10 min after ingestion (P< 0.01 vs phase III). Based on these characteristics a difference in IIR is to be expected, and the calculations revealed that IIR is considerably higher in the phase II series than in the phase III series (50 l/min x 120 min (8-90 l/min) vs -26 l/min x 120 min (-55 to 1 l/min), P< 0.001). In both series a weak but significant inverse relationship was demonstrated between amounts emptied during a 20-min period and the corresponding IIR (n = 72; r = -0.27, P< 0.05 (III); r = -0.29; P< 0.05 (II)). CONCLUSION: We conclude that fasting PFR is related to phase activity of the MMC and characteristics of the postprandial IIR depend upon MMC activity at the time of recording of the fasting value. Future studies on PFR need to be performed with phase related recording of fasting flow and meal ingestion in relation to preselected characteristics of the MMC.

Adult↗

[The Rockefeller Foundation, the Carlsberg Foundation and Danish medical biology in the interwar years. Effects on research and education throughout the 20th century].

Three large scientific institutes were built in Copenhagen, Denmark, between 1928 and 1938 supported by the Rockefeller Foundation in New York. The three institutes were: the Rockefeller Institute of Copenhagen, Juliane Mariesvej, the Biological Institute of the Carlsberg Foundation, and the Institute of Human Genetics, both on Tagensvej (The Carlsberg Foundation in Copenhagen participated in the financing of the two first ones.) In the same period the Rockefeller Foundation supported the construction of a cyclotron at Niels Bohr's Institute of Theoretical Physics. These institutes in Copenhagen sent many co-workers both to the Rockefeller University in New York and to other places in the world for further education supported by stipends from the Rockefeller Foundation. The scientific nucleus around which these activities crystallized included: the physiologist (and Nobel Prize winner) Aug. Krogh, the physicist (and Nobel Prize winner) Niels Bohr, the chemist S.P.L. Sorensen, the geneticist W. Johannsen, the plant physiologist Peter Boysen Jensen, and the cell culturist Albert Fischer. The international co-operation between the two foundations began early in the 20th century and it can be traced in Danish medical/biological science through the rest of that century.

Academies and Institutes↗