[Better analgesia to children].
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Age Factors↗
Biomedical subjects
K Berg
Publications and source records attributed to K Berg.
Protoporphyrin IX accumulation in cells treated with 5-aminolevulinic acid: dependence on cell density, cell size and cell cycle.
Human colon adenocarcinoma cells (WiDr) and Chinese hamster lung fibroblasts cells (V79) were incubated with different concentrations of 5-aminolevulinic acid (ALA), and the production of protoporphyrin IX (PpIX) was studied using several techniques. The amount of PpIX produced per cell increased with increasing ALA concentration according to different kinetics for the 2 cell lines. For both cell lines a cell density dependency of the PpIX synthesis was observed. For saturating ALA concentrations, 2-3 times more PpIX was produced per cell at a density of 5 x 10(4) than at a density of 5 x 10(3) cells/cm2. The photosensitivity of cells appeared to increase even more than the PpIX content, indicating a cooperative effect in inactivation. The PpIX production rate increased with cell size and was about 1.9 times higher for cells in the G2 + M phase than for cells in the G1 phase of the cell cycle. Neither cell size nor cell cycle distribution were significantly dependent on cell density.
Adenocarcinoma↗
Effects of a 9.6-kb deletion of the LDL receptor gene (FH Helsinki) on structure and levels of mRNA.
FH Helsinki is a deletion of the low-density lipoprotein receptor (LDLR) gene that deletes 9.6 kb from intron 15 to exon 18. Screening for mutant transcripts by Northern blot analysis from a patient heterozygous for FH Helsinki revealed two mutant transcripts. One was a transcript where the proximal part of intron 15 was retained in mRNA. The second was a transcript where exon 15 was spliced to nucleotide 4186 of exon 18. Thus, this transcript was generated using the normal donor splice site in intron 15, and a cryptic AG acceptor splice site in exon 18. Translation of the two mutant transcripts is predicted to give nonfunctional proteins, as both the membrane-spanning domain and the cytoplasmic domain of the receptor are deleted. Scanning of the autoradiograms showed that the amounts of each of the two mutant transcripts were approximately 10 times higher than that of the normal transcript in our heterozygous patient. The finding of higher levels of mutant transcripts was confirmed by an allele-specific transcript quantitation method, in which the amount of the two mutant transcripts together was approximately 5 times higher than the amount of the normal transcript. Deletion of destabilizing elements (AU-rich elements) by FH Helsinki are proposed to cause the increased levels of mutant transcripts.
Base Sequence↗
Screening for mutations of the apolipoprotein B gene causing hypocholesterolemia.
In this study we have performed analyses of apolipoprotein (apo) B at both the protein and gene level to search for mutations of the apoB gene causing hypocholesterolemia among 71 Norwegian subjects. None of the subjects possessed apoB of abnormal molecular weight as determined by SDS-polyacrylamide gel electrophoresis of lipoproteins in the 1.025 g/ml-1.063 g/ml density range. Screening for mutations in exon 26 of the apoB gene by analysis of single-strand conformation polymorphisms followed by DNA sequencing, revealed seven point mutations of which one is a novel mutation. Five of the mutations were missense mutations and two were sense mutations. A group of 143 hypercholesterolemic, nonfamilial hypercholesterolemia subjects served as a control group for comparisons of gene frequencies. The only statistically significant finding was that mutation 8344T at codon 2712 was more common among those with hypocholesterolemia. This finding is in accord with previous reports.
Adult↗
Benefits of home health care after inpatient rehabilitation for hip fracture: health service use by Medicare beneficiaries, 1987-1992.
OBJECTIVE: To examine the added benefit of home health services for elderly patients with hip fracture discharged home after inpatient rehabilitation. DATA: Medicare claims from 1% of 1986 beneficiaries followed until 1992. STUDY POPULATION: Persons hospitalized with hip fracture at 70 years or older who had no major Medicare claims during the year before hospitalization and who were discharged home after inpatient rehabilitation. OUTCOMES: Rehospitalization and any nonskilled nursing facility (non-SNF) nursing home admission during the 12 months after hospital discharge. RESULTS: Patients who received additional home health services (27.2%) were less likely to be hospitalized than those who received rehabilitation only (31.1%); they were also less likely to have a non-SNF nursing home admission (11.3% vs 23.3%), and more likely to survive the year with no subsequent Medicare claims (65.6% vs 55%). Propensity scores were used to adjust for nonrandom treatment selection in a Cox proportional hazards analysis showing that home health was associated with a significantly lower risk of nursing home admission (adjusted odds ratio = .42, 95% confidence interval .21-.84), and hospitalization (adjusted odds ratio = .65, 95% confidence interval .26-1.00). CONCLUSIONS: Studies of the relative effectiveness of post-acute services and postdischarge evaluations of inpatient rehabilitation should consider additional home care as a postacute service and examine optimal postacute treatment to minimize additional service use.
Aged↗
Liposome-bound Zn (II)-phthalocyanine. Mechanisms for cellular uptake and photosensitization.
In the present study, cellular uptake of a liposomal formulation of ZnPc (CGP 55847) has been studied in human cervix carcinoma cells of the line NHIK 3025. The cellular uptake of ZnPc is found to be completed after 4-8 h of incubation. The maximum level of ZnPc in the cells after incubation with 1 microgram/ml ZnPc in E2a medium containing 3% serum is 60 ng/mg protein. The cellular uptake is attenuated by the presence of serum and at low temperature of the incubation medium, but the activation energy (30 kJ/mol) and fluorescence microscopic analysis of cells incubated with ZnPc at 0 degree C indicate that ZnPc is taken up into cells by a diffusion-mediated pathway. Measurements of subcellular marker enzymes have been performed immediately after light exposure of ZnPc-treated cells. The mitochondrial marker enzyme (cytochrome c oxidase) and the marker enzyme for the Golgi apparatus (UDP galactosyl transferase), but not those for lysosomes (beta-N-acetyl-D-glucosaminidase) and endoplasmic reticulum (NADPH cytochrome c reductase), are inactivated upon photodynamic treatment. These results indicate that ZnPc is mainly located in the Golgi apparatus and the mitochondria of NHIK 3025 cells. In contrast, photoactivated Photofrin is found to reduce the activity of UDP galactosyl transferase, but not that of NADPH cytochrome c reductase. The tetraphenylporphine TPPS2a and light reduce the activity of NADPH cytochrome c reductase, without influencing the activity of UDP galactosyl transferase. TPPS4 and light do not attenuate the activities of UDP galactosyl transferase and NADPH cytochrome c reductase.
Drug Carriers↗
[Remifentanil in gynecologic laparoscopy. A comparison of consciousness and circulatory effects of a combination with desflurane and propofol].
OBJECTIVES: Rapid post-anaesthetic awakening and low hypnotic potency are two characteristic properties of the new opioid remifentanil. For clinical use remifentanil must be combined with another anaesthetic agent. Propofol is well-established for ambulatory anaesthesia, however, the properties of desflurane (low blood-gas solubility, rapid elimination) suggest this volatile anaesthetic to be a comparable alternative, particularly if rapid awakening is desired. The present study was designed to compare emergence times and haemodynamics for a combination of remifentanil wich hypnotic concentrations of either propofol or desflurane. METHODS: Gynaecological patients, scheduled for elective laparoscopy, were studied at random. After oral premedication with diazepam 0.08-0.12 mg/kg, anaesthesia was induced identically in both groups: remifentanil bolus (1 microgram/kg), start of remifentanil infusion (0.5 microgram/kg/min), followed by propofol (approx. 2 mg/kg) and cisatracurium (0.1 mg/kg). For maintenance of anaesthesia remifentanil (0.25 microgram/kg/min) was combined with either desflurane (0.5 MAC = 3.0 vol%) or propofol (6 mg/kg/h). With termination of surgery anaesthetic delivery was discontinued simultaneously and recovery times were recorded. Heart rate and non-invasive blood pressure were recorded at defined points of interest. RESULTS: In total, 40 patients (desflurane n = 20, propofol n = 20) were studied in comparable groups. For both regimens, emergence after remifentanil-based anaesthesia was remarkably rapid between unconsciousness and complete recovery: In mean only 60 s elapsed from the onset of spontaneous breathing to the moment when patients could clearly state their name. In comparison, recovery times were significantly shorter after remifentanil-desflurane than after remifentanil-propofol: time to spontaneous ventilation 6.4 +/- 2.8 vs. 9.6 +/- 3.9 min (mean +/- SD, p = 0.01); extubation 6.7 +/- 2.8 vs. 9.8 +/- 4.0 min (p = 0.02) and arrival at PACU 11.1 +/- 3.4 vs. 14.7 +/- 4.2 min (p = 0.005). The courses of heart rate (HR) and mean arterial pressure (MAP) were mostly similar in both groups with only minimal or moderate cardiocirculatory reactions during intubation or start of surgery. CONCLUSIONS: Remifentanil in combination with either desflurane or propofol, used for general anaesthesia during gynaecological laparoscopy, will facilitate a smooth haemodynamic course as well as a rapid emergence thereafter. Recovery times after remifentanil-based anaesthesia are significantly shorter with 3.0 vol% of desflurane than with 6 mg/kg/h propofol. Thus, desflurane appears to be a well-suited adjunct to remifentanil and an ideal alternative to propofol, if rapid recovery is required. Differences are best explained by the pharmacological properties of both coanaesthetics and their applied dosages.
Adult↗
Serum lipoprotein(a) and cardiovascular disease in non-insulin-dependent diabetes mellitus.
OBJECTIVE: To examine whether lp(a) can explain a) the increased cardiovascular morbidity in patients with non-insulin-dependent diabetes mellitus (NIDDM) and b) the wide variation in the tendency for such complications to develop in the patients. DESIGN: Cross-sectional study. SETTING: General practice in a local community in Norway. SUBJECTS: One hundred and thirty NIDDM patients and a reference group drawn from a twin study. MAIN OUTCOME MEASURES: Lp(a), self-reported cardiovascular disease, urinary albumin excretion. RESULTS: The level of lp(a) was equally distributed in our NIDDM population and a reference group. We found no association between lp(a) and self-reported cardiovascular disease and urinary albumin excretion (UAE). CONCLUSION: Lp(a) cannot explain the increased risk for cardiovascular disease in NIDDM patients, nor can it explain the variation in the tendency for such complications to develop.
Adult↗
Polymorphisms at the angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R) loci and normal blood pressure.
The M235T polymorphism at the angiotensinogen (AGT) locus and the A1166C polymorphism at the angiotensin II type 1 receptor (AT1R) locus have been reported to be associated with hypertension in several populations. We examined these polymorphisms in three samples of healthy Norwegians with respect to normal blood pressure (BP) levels. None of the genotypes defined by the polymorphisms or their combinations were associated with systolic (S) BP (SBP) or diastolic (D) BP (DBP) level. However, there was a trend in all three series that individuals carrying the C allele of the A1166C polymorphism at the AT1R locus (homozygotes as well as heterozygotes) had higher SBP, than AA homozygous individuals. The observation did not reach statistical significance in any of the series. When examining these two polymorphisms with respect to possible variability gene effects on BP in two series of monozygote (MZ) twin pairs, no such effect was detected. We could not detect any interaction between the loci studied with respect to BP level or variability. Thus, neither the AGT locus nor AT1R locus, separately analysed or together, seem to have variability gene effects or definite level gene effects on normal BP.
Analysis of Variance↗
Lack of an association between insulin-like growth factor-I and body composition, muscle strength, physical performance or self-reported mobility among older persons with functional limitations.
OBJECTIVE: The hypothesis that decreased growth hormone (GH) secretion contributes to the functional decline that occurs with aging is far from substantiated. There have been few studies addressing the distribution and correlates of IGF-I, an indicator of GH activity, in nonclinical populations. As part of a growth hormone intervention trial, we examined the cross-sectional relations between IGF-I levels and multiple measures of physical function, body composition, and strength in a group of older men and women exhibiting mild to moderate reductions in measured physical performance. METHODS: Using a variety of advertising techniques, 155 older subjects were recruited from a metropolitan area to participate in a growth hormone and exercise intervention study. At baseline, all subjects had blood drawn for IGF-I and underwent testing of body composition using dual X-ray absorptiometry, muscle strength using isokinetic dynamometry, and functional assessment using timed performance measures and self-report. Associations between levels of IGF-I, body composition, strength, and physical function were assessed after dividing men and women separately into tertiles of IGF-I as well as treating IGF-I as a continuous variable. RESULTS: Men had higher IGF-I levels than women, and a significant inverse correlation was observed between age and IGF-I in men (r=-0.29, P=.009). There were no clear trends for associations between tertiles of IGF-I, and any of the variables tested. Linear regression models with IGF-I treated as a continuous measure were not associated significantly with any of the measures of physical function, body composition, or strength (all P > 0.05). CONCLUSIONS: In conclusion, although IGF-I levels declined with age in men, these data did not demonstrate an association between IGF-I and measures of muscle strength, body composition, or physical functioning. These findings support the growing body of evidence that IGF-I levels may not be an indicator of growth hormone activity in older persons.
Aged↗
Age-dependent levels of select immunological mediators in sera of healthy children.
Serum cytokine levels were measured in 275 healthy children of different ages (3 to 17 years). Interleukin-1 receptor antagonist (IL-1RA), soluble IL-2R (sIL-2R) (sCD25), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), soluble TNF receptor type II (sTNF-RII) (sCD120b), gamma interferon (IFN-gamma), soluble intercellular adhesion molecule 1 (sICAM-1) (sCD54), soluble E selectin (sE-selectin) (ELAM-1; sCD62E), sCD14, and neopterin were measured with commercial test kits. The mean levels of IL-1RA, sIL-2R, TNF-alpha, sICAM-1, sE-selectin, and sCD14 were higher than in healthy adults. In contrast, IFN-gamma and IL-8 were hardly detectable in children and thereby significantly lower than in adults. In the case of TNF-alpha, sICAM-1, sE selectin, and sCD14, there was a high interindividual variability, apparently unrelated to disease. The profiles of some cytokines, i.e., IL-1RA, IL-6, and TNF-alpha, showed age-related increases that overlapped with known patterns of physical growth. Of note, sIL-2R and sE-selectin instead declined with time. Because of the remarkable age-dependent variability in healthy pediatric subjects, disease-related changes, as well as therapy-dependent alterations, should be considered with caution.
Adolescent↗
Induction of cytochrome P450 1A (CYP1A) in fish. A biomarker for environmental pollution.
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Animals↗
International Federation of Clinical Chemistry standardization project for the measurement of lipoprotein(a). Phase I. Evaluation of the analytical performance of lipoprotein(a) assay systems and commercial calibrators.
A secondary reference material for lipoprotein(a) is required to standardize the measurement of lipoprotein(a) in clinical laboratories worldwide. Towards this aim, the International Federation of Clinical Chemistry Working Group for the Standardization of Lipoprotein(a) Assays has initiated a standardization project involving a total of 33 diagnostic company and clinical chemistry laboratories from 12 countries. In Phase 1, the analytical performance of 40 lipoprotein(a) assay systems was evaluated by testing sera and manufactured lipoprotein(a) calibrator materials for precision, linearity, and parallelism. Twenty test systems were nonoptimized according to the results for a pooled serum, which tested nonlinear in 16 systems and imprecise in 4. Acceptable analytical properties and harmonization of lipoprotein(a) values were shown by some commercial calibrators, suggesting their possible use as reference materials. This study highlights the problems that currently occur for lipoprotein(a) measurement in existing assay systems.
Calibration↗
Relationship of somatotype and physical characteristics to distance running performance in middle age runners.
BACKGROUND: The purpose of this study was to determine the variance explained by somatotype, selected anthropometric variables, and muscle cross-sectional area (CSA) on 10 km run time. METHODS: Subjects were 19 female and 34 male moderately trained distance runners who competed in a local 10 km road race. Mean ages were 39.7 +/- 9.2 for females and 42.7 +/- 10.3 yr for males. RESULTS: Endomorphy explained 41.0% (R = 0.64, SEE = 6.5 min) of the variance in females' 10 km time, whereas body mass index explained 28.0% (R = 0.53, SEE = 7.8 min) with mesomorphy adding 10.4% (R = 0.62, SEE = 7.3 min) more explained variance in males' running times. With data combined for men and women, endomorphy explained 22.1% (R = 0.47, SEE = 7.9 min) of the variance. CONCLUSIONS: It was concluded that somatotype and body mass index explain a moderate portion of the variance in 10 km run performance in runners heterogeneous in ability. Muscle and muscle plus bone cross-sectional area of related running muscles does not contribute to the explained variance in men. Research seeking to explain sources of variation in running performance should consider including somatotype as an independent variable.
Adult↗
Cholesterol-lowering therapy in women and elderly patients with myocardial infarction or angina pectoris: findings from the Scandinavian Simvastatin Survival Study (4S)
BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) demonstrated pronounced reductions in mortality and major coronary events in a cohort of patients with established coronary heart disease (CHD). The present study provides a detailed, post hoc assessment of the efficacy and safety of simvastatin therapy in the following subgroups of 4S patients: those > or = 65 years of age, those < 65 years of age, women, and men. METHODS AND RESULTS: The 4S cohort of 4444 CHD patients included 827 women and 1021 patients > or = 65 years of age. Total cholesterol at baseline was 5.5 to 8.0 mmol/L with triglycerides < or = 2.5 mmol/L. Patients were randomized to therapy with simvastatin 20 to 40 mg daily or placebo for a median follow-up period of 5.4 years. End points consisted of all-cause and CHD mortality, major coronary events (primarily CHD death and nonfatal myocardial infarction), other acute CHD and atherosclerotic events, hospitalizations for CHD and cardiovascular events, and coronary revascularization procedures. Mean changes in serum lipids were similar in the different subgroups. In patients > or = 65 years of age in the simvastatin group, relative risks (95% confidence intervals) for clinical events were as follows: all-cause mortality, 0.66 (0.48 to 0.90); CHD mortality, 0.57 (0.39 to 0.83); major coronary events, 0.66 (0.52 to 0.84); any atherosclerosis-related event, 0.67 (0.56 to 0.81); and revascularization procedures, 0.59 (0.41 to 0.84). In women, the corresponding figures were 1.16 (0.68 to 1.99); 0.86 (0.42 to 1.74), 0.66 (0.48 to 0.91), 0.71 (0.56 to 0.91), and 0.51 (0.30 to 0.86), respectively. CONCLUSIONS: Cholesterol lowering with simvastatin produced similar reductions in relative risk for major coronary events in women compared with men and in elderly (> or = 65 years of age) compared with younger patients. There were too few female deaths to assess the effects on mortality in women. Because mortality rates increased substantially with age, the absolute risk reduction for both all-cause and CHD mortality in simvastatin-treated subjects was approximately twice as great in the older patients.
Adult↗
[Do not forget the other half of the organ! Important to examine balance of deaf and hearing impaired persons].
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Adolescent↗
5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges.
BACKGROUND: Photodynamic therapy (PDT) for cancer patients has developed into an important new clinical treatment modality in the past 25-years. PDT involves administration of a tumor-localizing photosensitizer or photosensitizer prodrug (5-aminolevulinic acid [ALA], a precursor in the heme biosynthetic pathway) and the subsequent activation of the photosensitizer by light. Although several photosensitizers other than ALA-derived protoprophyrin IX (PpIX) have been used in clinical PDT, ALA-based PDT has been the most active area of clinical PDT research during the past 5 years. Studies have shown that a higher accumulation of ALA-derived PpIX in rapidly proliferating cells may provide a biologic rationale for clinical use of ALA-based PDT and diagnosis. However, no review updating the clinical data has appeared so far. METHODS: A review of recently published data on clinical ALA-based PDT and diagnosis was conducted. RESULTS: Several individual studies in which patients with primary nonmelanoma cutaneous tumors received topical ALA-based PDT have reported promising results, including outstanding cosmetic results. However, the modality with present protocols does not in general, appear to be superior to conventional therapies with respect to initial complete response rates and long term recurrence rates, particularly in the treatment of nodular skin tumors. Topical ALA-PDT does have the following advantages over conventional treatments: it is noninvasive; it produces excellent cosmetic results; it is well tolerated by patients; it can be used to treat multiple superficial lesions in short treatment sessions; it can be applied to patients who refuse surgery or have pacemakers and bleeding tendency; it can be used to treat lesions in specific locations, such as the oral mucosa or the genital area; it can be used as a palliative treatment; and it can be applied repeatedly without cumulative toxicity. Topical ALA-PDT also has potential as a treatment for nonneoplastic skin diseases. Systemic administration of ALA does not seem to be severely toxic, but the advantage of using this approach for PDT of superficial lesions of internal hollow organs is still uncertain. The ALA-derived porphyrin fluorescence technique would be useful in the diagnosis of superficial lesions of internal hollow organs. CONCLUSIONS: Promising results of ALA-based clinical PDT and diagnosis have been obtained. The modality has advantages over conventional treatments. However, some improvements need to be made, such as optimization of parameters of ALA-based PDT and diagnosis; increased tumor selectivity of ALA-derived PpIX; better understanding of light distribution in tissue: improvement of light dosimetry procedure; and development of simpler, cheaper, and more efficient light delivery systems.
Aminolevulinic Acid↗
Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture.
Human tumor cells of the lines WiDr (adenocarcinoma of the rectosigmoid colon), NHIK 3025 (carcinoma of the cervix), and V79 Chinese hamster fibroblasts were treated with 5-aminolevulinic acid (ALA) and ALA esterified to C1-C3 and C6-C8 chained aliphatic alcohols (ALA-esters). In the human cell lines, esterification of ALA with the long-chain (C6-C8) alcohols was found to reduce 30-150-fold the amount of ALA needed to reach the same level of protoporphyrin IX (PpIX) accumulation as with non-esterified ALA. The long-chained ALA-esters were less efficient in stimulating PpIX formation in V79 cells, i.e., the same amount of PpIX was formed by a 1-2.6-fold lower concentration of long-chained ALA-esters than with ALA. Short-chained ALA-esters (C1-C3) induced 5 to 10 times lower PpIX accumulation than ALA in all of the cell lines. High-performance liquid chromatography and fluorescence microscopic studies indicated that esterification of ALA has neither impact on the fluorescing porphyrin species formed nor impact on their intracellular localization. The PpIX formed from ALA-esters and ALA was found to be equally efficient in sensitizing cells to photoinactivation. The present results indicate that esterified ALAs are new and promising drugs for use in photochemotherapy of cancer.
Adenocarcinoma↗