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Biomedical subjects

L Larsen

Publications and source records attributed to L Larsen.

At least 19 recordsLinked to original sources

Magnetic resonance investigation of bone marrow following priming and stem cell mobilization.

PURPOSE: To evaluate application of MRI and magnetic resonance spectroscopy (MRS) to monitor bone marrow cellularity during pretransplant priming with chemotherapy and hematopoietic growth factor (HGF) administration. MATERIALS AND METHODS: A total of 10 lymphoma and myeloma patients, in remission following induction therapy and considered eligible for high-dose therapy and autologous stem cell transplantation, were included in the study. MR investigation was scheduled four times: at study entry, and one, two, and four weeks following priming. Priming with cyclophosphamide and recombinant human granulocyte colony-stimulating factor (rhG-CSF) started the day after study entry. MR parameters studied in a region of interest were as follows: bone marrow intensity on short-time inversion-recovery (STIR) turbo spin-echo (TSE; thus STIRTSE) and on T1-weighted TSE (T1TSE) images, T2 value for fat component, T2 value for water component, water/fat ratio (W/F), T1 value for fat component, and T1 value for water component. RESULTS: The results did not support the hypothesis that hematopoietic expansion quantitated and monitored by MR correlates to the level of mobilized progenitor cells. CONCLUSION: The results indicate that release of stem cells is a more complex phenomenon than hematopoietic expansion and reduction of fat tissue in bone marrow.

Aged↗

Childhood obesity: prevention practices of nurse practitioners.

PURPOSE: The purposes or this study were to (a) describe the prevention practices of nurse practitioners (NPs) regarding childhood obesity, (b) compare the practices of NPs by specialty, practice setting, and awareness of childhood obesity prevention guidelines, (c) identify relationships between prevention practices and demographic variables of NPs, and (d) examine the resources for and barriers to implementing prevention practices. DATA SOURCES: A convenience sample of 99 family NPs (FNPs) and pediatric NPs (PNPs) from the Intermountain area was used. Participants completed a questionnaire based on documented risk factors for childhood obesity as well as prevention guidelines developed by the American Academy of Pediatrics (AAP). CONCLUSIONS: NPs working in family practice or general pediatric practice settings were not consistently using the BMI-for-age index to screen for childhood obesity, as recommended by the AAP. However, they were teaching parents to promote healthy food choices and physical activity in their families. PNPs and FNPs working in a pediatric practice setting and NPs who were aware of prevention guidelines were more likely to perform several prevention strategies than FNPs working in a family practice setting and those who were unaware of guidelines. Major barriers to implementing childhood obesity prevention strategies included parental attitudes, the American lifestyle, and lack of resources for both the NP and the family. The main resources NPs used in preventing childhood obesity were a dietician, journal articles, and Web sites. IMPLICATIONS FOR PRACTICE: Although the majority of the NPs in this study reported being aware of childhood obesity prevention guidelines (73.7%), most were not consistently using BMI for age or monitoring children at increased risk for obesity. Because childhood obesity is escalating at such a rapid rate, it is critical that NPs working in family practice and pediatric practice settings take the necessary steps to help curtail obesity in childhood, including calculating BMI for age, targeting children at risk, and helping families develop healthy nutrition and physical activity habits. In addition to proper health supervision of children, NPs also need to be advocates in their communities to overcome barriers to childhood obesity prevention.

Adult↗

Extracellular signal-regulated kinase is essential for interleukin-1-induced and nuclear factor kappaB-mediated gene expression in insulin-producing INS-1E cells.

AIMS/HYPOTHESIS: The beta cell destruction and insulin deficiency that characterises type 1 diabetes mellitus is partially mediated by cytokines, such as IL-1beta, and by nitric oxide (NO)-dependent and -independent effector mechanisms. IL-1beta activates mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK), and the nuclear factor kappa B (NFkappaB) pathway. Both pathways are required for expression of the gene encoding inducible nitric oxide synthase (iNOS) and for IL-1beta-mediated beta cell death. The molecular mechanisms by which these two pathways regulate beta cell Nos2 expression are currently unknown. Therefore, the aim of this study was to clarify the putative crosstalk between MAPK and NFkappaB activation in beta cells. MATERIALS AND METHODS: The MAPKs ERK, p38 and JNK were inhibited by SB203580, PD98059 or Tat-JNK binding domain or by cells overexpressing the JNK binding domain. The effects of MAPK inhibition on IL-1beta-induced iNOS production and kappa B inhibitor protein (IkappaB) degradation were examined by western blotting. NFkappaB DNA binding was investigated by electrophoretic mobility shift assay, while NFkappaB-induced gene transcription was evaluated by gene reporter assays. RESULTS: Inhibition of the MAPKs did not affect IkappaB degradation or NFkappaB DNA binding. However, inhibition of ERK reduced NFkappaB-mediated Nos2 expression; serine 276 phosphorylation of the p65 unit of the NFkappaB complex seemed critical, as evaluated by amino acid mutation analysis. CONCLUSIONS/INTERPRETATION: ERK activity is required for NFkappaB-mediated transcription of Nos2 in insulin-producing INS-1E cells, indicating that ERK regulates Nos2 expression by increasing the transactivating capacity of NFkappaB. This may involve phosphorylation of Ser276 on p65 by an as yet unidentified kinase.

Animals↗

Building-related symptoms and molds: a two-step intervention study.

AIMS: To evaluate the relation between mold growth and symptoms in an intervention study design. METHODS: The building was examined by a walk-through and microbiological testing from surfaces and ventilation canals before and after each of two steps of the renovation. The examination program for the 25 employees comprised questionnaire, clinical examination, 2-week peak-flow monitoring, and blood samples, and in six persons also a bronchial challenge. RESULTS: Initially the building had severe moisture problems with growth of Trichoderma and Phoma as dominating microfungi. The total number of symptoms from a nine-item building-related symptom score was 66%, peak-flow variability was 20%. After the first renovation, no visible mold growth was seen, but samples showed that the building was still contaminated. Symptoms decreased to 33%. After further cleaning the mold levels decreased on surfaces, and the number of symptoms decreased to 4%. Mean peak-flow variability fell to 15%. DISCUSSION: In a poorly maintained building with moisture problems and mold growth, the staff had a number of irritative and general symptoms. The first renovation eradicated most visible signs of molds and gave a decreased number of symptoms. The second renovation sufficiently cleaned the building, and the rate of symptoms and peak-flow variability fell to normal levels. A thorough cleaning after renovation seems necessary for the eradication of symptoms.

Air Pollution, Indoor↗

Evaluation of chronic venous disease in the lower limbs: comparison of five diagnostic methods.

To compare the usefulness of five diagnostic methods in ensuring deep vein patency, and in demonstrating site(s) of incompetence, 39 patients with clinical signs of chronic venous disease of a leg were included in a study of deep, superficial and perforator veins using triplex ultrasound (TUS), ascending phlebography (AP), descending phlebography (DP), continuous wave Doppler (CWD) and ambulatory strain gauge plethysmography (ASGP). One patient withdrew from the study. It was not possible to use all five methods in all 38 cases, and the methods could only be used partly in some cases. TUS, which allows anatomical, morphological and functional evaluation of the venous system, was chosen as the reference method. There was poor agreement between TUS and AP, and no agreement between TUS and ASGP, in the diagnosis of venous occlusion. AP demonstrated reflux (abnormal valves) in 7 of 22 patients with competent veins at TUS, and missed reflux in 13 of 15 patients with incompetent veins. Similarly, CWD overdiagnosed reflux in 13 of 20 patients and missed the reflux in 3 of 14 patients. DP was only technically possible in 11 patients. ASGP diagnosed venous reflux in all patients with incompetent deep veins, but also indicated deep vein or perforator vein reflux in all but one patient with competent deep veins. The agreement between TUS and the other methods in evaluating reflux in the deep veins was not better than that expected to occur by chance, Cohen's kappa being less that 0.20. It is concluded that AP, CWD and ASGP are of little value in the work-up of patients with deep venous insufficiency.

Adult↗

The effect of nevirapine in combination with nelfinavir in heavily pretreated HIV-1-infected patients: a prospective, open-label, controlled, randomized study.

The purpose of the current study was to determine the efficacy and safety of nevirapine combined with nelfinavir and two nucleoside reverse transcriptase inhibitors (NRTIs) in patients previously exposed to highly active antiretroviral therapy (HAART). In a prospective, open-label, randomized study, 56 HIV-infected adults who had received HAART, including saquinavir hard gel capsule, ritonavir, or indinavir, were randomly assigned to receive nevirapine in addition to nelfinavir and two NRTIs. The proportion of patients who achieved an undetectable viral load (plasma HIV-RNA <200 copies/ml) at weeks 24 and 36 was significantly higher in the nevirapine group than in the control group (55% and 52% vs. 22% and 22%; p =.015 and p =.047). No differences in CD4 cell count or clinical outcome were observed. In the nevirapine group, 17% of patients discontinued treatment because of rashes. We conclude that the addition of nevirapine, when switching from one protease inhibitor-containing regimen to one containing nelfinavir, has a substantial effect on viral suppression.

Adult↗

Intranasal absorption of sumatriptan and naratriptan: no evidence of local transfer from the nasal cavities to the brain arterial blood in male rats.

Nasal administration to rats of small molecules (tritiated water, tyrosine, and propanol) results in a higher concentration in the brain arterial blood than in other arteries. The preferential distribution is based on a counter current transfer, which takes place between nasal vein blood and brain arterial blood in the cavernous sinus-carotid artery complex. This model was used to investigate whether the antimigraine 5HT(1B/1D) receptor agonists sumatriptan and naratriptan may also be transferred by the system. The ratio of 'head':'heart' plasma concentrations obtained from two carotid catheters after intranasal administration was not different from 1.00 for either compound, and thus, there was no experimental evidence of a preferential local transfer of drug from the nose to the carotid artery circulation. However, plasma concentrations increased from the first minute after intranasal dosing suggesting that sumatriptan and naratriptan are absorbed into the general systemic circulation from the nasal cavity in rats in a first-order fashion with no lag time. This is consistent with the clinical onset of efficacy of sumatriptan after an intranasal dose which occurs as early as 15 min post dose.

Absorption↗

Analysing transformation products of herbicide residues in environmental samples.

High-performance liquid chromatography (HPLC) methods were developed for the optimised determination of five herbicide residues (dichlorprop, isoproturon, mecoprop, metsulfuron-methyl and 2,4,5-T) and major metabolites. These compounds represent important groups of herbicides and several residues have been found as contaminants in groundwater. The methods make it possible to study these herbicides and several transformation products through simultaneous detection and quantification. Culture media as well as cleaned up extracts from sediment and groundwater can be analysed. Using HPLC with UV detection the general limit of quantification was 1.8 ng injected corresponding to a detection limit of 1-2 micrograms/l when analysing a cleaned up extract from a 20 ml water sample. The method was verified by analysing herbicide residues in groundwater collected from a wetland area. Cleaning up 20 ml groundwater with a residue level of 25 micrograms/l the general recovery was within 58-82%.

Chromatography, High Pressure Liquid↗

Degradation of herbicides in two sandy aquifers under different redox conditions.

We examined the potential for complete degradation (mineralisation) of the four [ring-U-14C]herbicides mecoprop, isoproturon, atrazine, and metsulphuron-methyl in two sandy aquifers representing aerobic, denitrifying, sulphate-reducing, and methanogenic conditions. Slurries with sediment and groundwater were set-up aerobically or anaerobically in the presence of the electron-acceptor prevailing at the sampling site, amended with 25 microg l(-1) herbicide, and incubated at 10 degrees C. Considerable mineralisation was only observed in sediment from the plough layer incubated aerobically. Here, 30% of 14C-mecoprop was recovered as 14CO2 after 15 days and 15% of isoproturon was recovered as 14CO2 after 267 days. Only 7% of mecoprop was recovered as 14CO2 after 313 days in sediment from the aquifer below sampled at 1.95-3.00 mbs (m below the surface). In denitrifying and methanogenic slurries, 3% of 14C added as mecoprop was recovered as 14CO2. Isoproturon was not mineralised except in the aerobic plough layer, and atrazine and metsulphuron-methyl were not mineralised under any of the conditions applied.

Biodegradation, Environmental↗

Oppositional defiant disorder with onset in preschool years: longitudinal stability and pathways to other disorders.

OBJECTIVE: To examine the stability and change in oppositional defiant disorder (ODD) with onset among preschool children in a pediatric sample. METHOD: A total of 510 children aged 2-5 years were enrolled initially in 1989-1990 (mean age 3.42 years); 280 participated in five waves of data collection over a period of 48 to 72 months (mean wave 5 age, 8.35 years). Test batteries varied by age, but they included the Child Behavior Checklist, developmental evaluation, Rochester Adaptive Behavior Inventory, and a play session (before age 7 years) and a structured interview (Diagnostic Interview for Children and Adolescents, parent and child versions) at ages 7+ years. Consensus diagnoses were assigned by using best-estimate procedures. RESULTS: Wave 1 single-diagnosis ODD showed a significant relationship with both single-diagnosis ODD and single-diagnosis attention-deficit hyperactivity disorder (ADHD) at subsequent waves, but not with single-diagnosis anxiety or mood disorders. Single-diagnosis ODD at wave 1 was associated with later comorbidity of ODD/ADHD, ODD/anxiety, and ODD/mood disorders. Stability across waves 2 through 5 was moderate to high for comorbid ODD/anxiety and ODD/ADHD; low to moderate stability for single-diagnosis ODD and single-diagnosis mood disorder; and low for mood disorder, single-diagnosis ADHD, and single-diagnosis anxiety disorder. CONCLUSIONS: Preschool children with ODD are likely to continue to exhibit disorder, with increasing comorbidity with ADHD, anxiety, or mood disorders.

Adaptation, Psychological↗

Transfer of tritiated water, tyrosine, and propanol from the nasal cavity to cranial arterial blood in rats.

Respiration cools the nasal vein blood. This may, via counter current transfer in the cavernous sinus/carotid artery complex, cool the brain arterial blood and, therefore, decrease the brain temperature during heat stress. We investigated the possible local transfer of substances from the nasal cavities to the brain via a similar transfer between nasal venous blood and brain arterial blood. Tritiated water (TW), 3H-tyrosine (T) and 14C-propanol (P) were infused into the nasal cavity of anesthetized rats that had two catheters inserted into the same, occluded carotid artery, one pointing towards the head, the other towards the heart. Continuous, parallel blood samples were collected throughout 30-s periods for 10 min, and the radioactivity measured in the separated plasma. After nasal application of TW, the radioactivity increased in the head arterial plasma samples compared with the parallel heart samples. When recirculation to the general circulation was diminished, a larger and significant difference was found for all three substances during the last 5 min of the collection period. No difference between the parallel samples was observed after intravenous administration of the three substances. Absorption of all three substances from the nasal cavity was rapid and high. The results indicate that local transfer takes place between the venous and arterial blood in the head, probably in the area of the cavernous sinus-carotid artery complex, which in rat and man lacks a Rete Mirabile. The local transfer raises the possibility of treating brain diseases in man locally through nasal application of drugs.

1-Propanol↗

A cytotoxic sesquiterpene caffeate from the liverwort Bazzanianovae-zelandiae.

Extracts of the liverwort Bazzania novae-zelandiae were cytotoxic, with selective activity against human tumor cell lines. Bioactivity-directed isolation work showed that the new compound naviculyl caffeate (1) was the main cytotoxin. This structure was confirmed by synthesis from the co-occurring sesquiterpene naviculol (2).

Antineoplastic Agents, Phytogenic↗

Local transfer of diazepam, but not of cocaine, from the nasal cavities to the brain arterial blood in rats.

Nasal administration to rats of small molecules (tritiated water, tyrosine, and propanol) results in a higher concentration in the brain arterial blood than in other arteries. The preferential distribution is based on a counter current transfer, which takes place between nasal vein blood and brain arterial blood in the cavernous sinus-carotid artery complex. The present experiments attempt to document that drugs may also be transferred by this system. Groups of 10 large male rats were anaesthetised and intubated. Two catheters were inserted into the same carotid artery, one tip pointing towards the head, the other towards the heart. Parallel blood samples were obtained every 30 sec. for 10 min. after nasal administration of radioactively labelled diazepam or cocaine, and the plasma radioactivity measured. Control groups received the drugs intravenously. The uptake of diazepam was rapid, while cocaine uptake was slow. The average ratio between the radioactivity of parallel samples (R: "Head" plasma/"Heart" plasma) in rats treated with nasal diazepam was 1.12+/-0.04, 181 (average+/-S.E.M., n) for the whole 10 min. period and 1.20+/-0.05, 96 for the second half of the sampling period. The increase of 12 and 20% is highly significant. The intravenous ratio for diazepam and both R's for the cocaine groups were not significantly different from 1.00. The present experiments show that nasal administration of diazepam induces a relatively higher concentration in the brain arterial blood than in parallel samples obtained from another artery. A preferential, first-pass distribution to the brain after nasal administration of diazepam may thus exist.

Animals↗

Computer-assisted semen analysis parameters as predictors for fertility of men from the general population. The Danish First Pregnancy Planner Study Team.

The predictive value of sperm motility parameters obtained by computer-assisted semen analysis (CASA) was evaluated for the fertility of men from general population. In a prospective study with couples stopping use of contraception in order to try to conceive, CASA was performed on semen samples from 358 men. A recently developed CASA system, Copenhagen Rigshospitalet Image house sperm Motility Analysis System (CRISMAS) was used for assessment of motility parameters. This system has an editing function which allows correction of tracks made by the computer. Probably due to this function, the concentration assessment made by CRISMAS was very close to that made by the technician (median difference <5%) in all concentration ranges. Correlation between CASA parameters and fertility of normal couples (measured as probability of achieving pregnancy) was examined by the Cox regression model. In univariate models ln(sperm concentration) [beta = 0.331, risk ratio (RR) = 1.392, P = 0.0001], ln(total sperm count) (beta = 0.252, RR = 1.286, P = 0.0007) and percentage motile spermatozoa (beta = 0.014, RR = 1.014, P = 0.0004) were most significant predictors for fertility. In a multivariate analysis ln(sperm concentration) (beta = 0.268, RR = 1.307, P = 0.0016) and percentage motile spermatozoa (beta = 0.010, RR = 1.010, P = 0.011) but even more significantly the combined parameter, ln(concentration of motile spermatozoa) (beta = 0.329, RR = 1.389, P = 0.0001), were the only parameters of predictive value for fertility of men in the general population. In conclusion, these parameters obtained by CASA measurements can be used for prediction of fertility potential in normal men. This appears to be the first study showing the value of CASA in prediction of fertility in the general male population.

Adult↗

Integrating emergency services in an urban health system.

When planning for growth and management efficiency across urban health systems, economic and market factors present significant service line challenges and opportunities. This article describes the evolutionary integration of emergency services in St John Health System, a large, religious-sponsored health care system located in Detroit, Michigan. Critical business elements, including the System's vision, mission, and economic context, are defined as the framework for site-specific and System-wide planning. The impact of managed care and market changes prompted St John's clinicians and executives to explore how integrating emergency services could create a competitive market advantage.

Continuity of Patient Care↗

[Treatment of HIV infections and AIDS with protease inhibitor and two nucleoside analogs].

Until December 31st 1997, 163 HIV/AIDS patients were treated with HAART at the Department of Infectious Diseases, Aarhus University Hospital. The patients mainly received a combination of zidovudine, lamivudine and saquinavir. They were observed for an average period of 375 days. HAART was found to increase the amount of CD4 lymphocytes in peripheral blood and decrease the number of HIV-RNA copies. Both effects were seen to be more pronounced in patients naive to antiretroviral treatment. However, 64 patients had their protease inhibitor changed during the observation period, 53% due to failure of suppression of the viral load, 25% due to adverse events and 22% due to other reasons.

Acquired Immunodeficiency Syndrome↗

Saquinavir hard gel suppresses viral load insufficiently in HIV-infected patients naive to anti-retroviral therapy: a retrospective cohort study.

Protease inhibitors are important components in anti-retroviral regimens. In this retrospective study 29 HIV-infected patients treated with a regimen of zidovudine, lamivudine and saquinavir hard gel in 1 centre in Denmark were compared with 58 patients treated with zidovudine, lamivudine and ritonavir or indinavir followed at 5 other centres in Scandinavia. All patients were naive to anti-retroviral therapy prior to institution of the actual anti-retroviral regimen and were followed for a median of 1.3 and 1.4 y respectively. The 2 groups did not differ significantly with respect to age, gender, route of infection, ethnic background, viral load, CD4 count, AIDS at baseline or frequency of clinical controls. Six and 12 months after initiating anti-retroviral therapy, 31% and 34% of the patients on the saquinavir regimen obtained HIV-RNA < or = 500 compared with 76% and 73% in the control group (p < 0.001). In contrast to viral load, the increase in CD4 count did not differ significantly between the 2 groups. In conclusion, we found that with respect to suppression of viral load a regimen of saquinavir, zidovudine and lamivudine seemed to be inferior to a regimen of zidovudine, lamivudine and ritonavir or indinavir.

Adult↗

Supersmart homes: a new meaning for home care.

In 1908, when four nurses first began to deliver inhome nursing services in Toronto, Ontario, no one realized the organization would experience so much change and opportunity to enhance the care provided to clients and their families. Now, almost a century later, information and communications technologies are enabling an entirely different way of providing health services and supports, including information that promotes self management and more control for clients over their own health and health care.

Canada↗