Analysis of RNA synthesis by cytometry.
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Biomedical subjects
Publications and source records attributed to J Larsen.
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This is the first Swedish study to evaluate the health-related quality of life and sense of coherence in adult survivors of allogeneic, haematopoietic stem cell transplantation (HSCT). Twenty-five recipients completed three questionnaires 2-4 years after the transplantation. The questionnaires used were the Sickness Impact Profile (SIP), the Symptom Frequency Intensity and Distress (SFID-BMT) scale and the Sense of Coherence (SOC) scale measuring subjective functional status, symptom distress and coping ability. Impairments in functional status were found, as compared with a population norm. The most common impairments were found in the areas of social interaction and sleep and rest. Eye problems, dry mouth, cough, sexual problems, tiredness, anxiety and changes of taste were symptoms reported by more than half of the patients. Despite impaired functioning and a high incidence of symptoms, the general health was described as quite good or excellent by 80% (n = 20) of the patients. The majority (20/22) had also been able to return to work or to attend school. No difference in the sense of coherence was seen, as compared with the population norm. Functional impairments were significantly correlated to a lower degree of sense of coherence.
OBJECTIVE: To analyse the effect of guidelines accompanied by changes in reimbursement rules for the prescription of lipid-lowering drugs (LLDs). DESIGN: Observational study focusing on LLD use before (1994-98) and after an intervention (1999). SETTING: Guidelines were developed by the Danish College of General Practitioners and focused on prevention of cardiovascular heart disease (CHD). Guidelines were sent out and changes in reimbursement took place in December 1998. Prescriptions for LLDs were extracted from a population-based prescription database (Odense University Pharmacoepidemiological Database, OPED) covering 10% of the Danish population (470,000 inhabitants). MAIN OUTCOME MEASURES: Incidence rate and 1 year prevalence rate (annual prevalence) of LLD use. RESULTS: The incidence of LLD use increased significantly in the year following the intervention. Incidence rate ratio (after/before) was 1.43 (CI 1.35-1.52). The annual prevalence of LLD use in the population increased by 0.4% after the intervention (0.2% before). The corresponding figure for patients with diabetes mellitus (treated with insulin or oral anti-diabetics) was 2.3% after the intervention (1.2% before), and for patients with CHD (treated with vasodilators) 8.1% after the intervention (5.0% before). CONCLUSION: Guidelines accompanied by a change in reimbursement rules had a significant influence on the prescribing of lipid-lowering drugs.
OBJECTIVE: Investigation of the cost-effectiveness of intravascular ultrasound (IVUS) guided percutaneous coronary intervention (PCI) compared to PCI guided by coronary angiography (CAG). METHODS: One hundred and eight men referred for PCI, were randomized to IVUS or CAG guided PCI. After 6 months, the patients were subjected to a study related clinical and invasive follow-up investigation by CAG, IVUS and intracoronary Doppler flow measurements. Incremental costs of IVUS guided procedures and costs of re-interventions were estimated using the Activity Based Costing (ABC) method. RESULTS: Patients randomized to IVUS guided PCI experienced an improved clinical outcome, with lower angina levels than patients in the CAG guided group. The initial cost of performing IVUS guidance was increased due to extra procedure time, IVUS catheters and slightly more balloons and stents, but fewer patients in the IVUS guided group needed re-intervention. Overall, these savings outweighed the initial cost increase. CONCLUSION: Our data suggest that when performing IVUS guided PCI, costs as well as benefits increase. The increased benefits measured as cost savings resulting from less restenosis outweigh the cost increase from performing the IVUS guided PCI as opposed to CAG guided PCI.
BACKGROUND: Collaboration refers to a process in which family expertise is acknowledged and used to direct selection, implementation, and evaluation of treatment plans. Although the skills required to create collaborative partnerships with families are a mainstay of practice for certain rehabilitation disciplines, others have traditionally worked in client-clinician dyads that emphasize the role of the professional as responsible for client change. In addition, the existing collaborative models for working with families affected by brain injury require intensive resources and supports, making collaborative partnerships difficult to create within today's clinical and educational service delivery environments. RESULT: In this article, we report our efforts to create an accessible set of collaboration procedures for rehabilitation professionals working in clinical and educational settings with individuals with brain injury and their families. A 2-year, qualitative study with eight families led to the development of a preliminary model and prescriptive manual for applying collaborative principles to practice. CONCLUSION: We review the components of the model and implications for practice.
BACKGROUND: Prolonged QT offset dispersion (QToD), an index of heterogeneity of ventricular repolarization, is thought to be an independent predictor of all-cause and cardiovascular mortality. However the influence of gender and autonomic tone in healthy adults on age-related changes in measures of ventricular repolarization are not well characterized. METHODS: QToD and T wave complexity were measured in 56 healthy subjects with no detectable heart disease (by echo and stress test)-38 young subjects with a mean age of 28 +/- 4 years and 18 old subjects with a mean age of 71 +/- 7 years. QToD and T wave complexity were computed from 12-lead ECGs using the GE Marquette QT Guard automated analysis program with manual overreading at rest (baseline), following exercise, and double autonomic blockade with atropine and propranolol. Data was analyzed using factorial ANOVA. RESULTS: Young males had a significantly greater QToD than young and old females at baseline (28 +/- 5 ms, 23 +/- 5 ms, and 22 +/- 5 ms, respectively, P < 0.01), an intrinsic effect independent of changes in autonomic tone. In contrast, females had significantly greater T wave complexity than males following exercise and double autonomic blockade with a definite trend at baseline. There was no correlation between T wave complexity and QToD. CONCLUSIONS: Age and gender demonstrate a complex interaction on indices of myocardial repolarization with different measures behaving differently. These findings have implications for better understanding age and gender effects on myocardial electrophysiology.
We investigated if any change in spatial resolution of comparative genomic hybridization analysis could be detected when using DNA amplified by degenerate oligonucleotide primed PCR (DOP-PCR) as opposed to the use of unamplified DNA. Five DNA samples from B-cell leukemias with small 11q deletions were amplified by DOP-PCR and analysed by means of high resolution comparative genomic hybridization (HR-CGH) for the evaluation of aberration size detection limit. By means of HR-CGH, we found the detection limit of DOP-PCR CGH for deletions to be between 3 Mbp and 7-8 Mbp.
OBJECTIVE: To assess the efficacy and safety of glucagon-like peptide-1 (GLP-1) on the plasma glucose level when given as a continuous infusion for either 16 or 24 h per day to type 2 diabetic patients who were poorly controlled on sulfonylurea treatment. RESEARCH DESIGN AND METHODS: This single-center, randomized, parallel, double-blind, placebo-controlled trial was conducted in 40 hospitalized patients who were randomized to receive infusions of either placebo or GLP-1 4 or 8 ng. kg(-1). min(-1) for either 16 or 24 h per day for 7 days. At predetermined intervals, 24-h profiles of glucose, glucagon, and insulin were measured. Adverse events and clinical chemistry and hematology were recorded. RESULTS: For all active treatment groups, the change in average glucose (area under the curve [AUC] for day 7 minus AUC for day 0 divided by 24 h) was statistically significantly different from placebo (P < or = 0.001). The GLP-1 8 ng. kg(-1). min(-1) dose given for 24 h was more efficacious than any of the other doses (P < or = 0.05). Nocturnal and fasting plasma glucose levels at day 7 were greater in the 16-h groups compared with the 24-h groups (P < or = 0.05). Insulin AUC did not show any treatment effect for any of the treatment groups when change was assessed from day 0 to day 7. However, for the 16-h groups, the pattern of the insulin profiles changed; the insulin profiles were considerably higher during the initial 3-4 h after restart of the GLP-1 infusion on day 7, although there was a tendency for insulin levels to decrease during the afternoon and evening. Glucagon AUC decreased significantly for all active treatment groups compared with placebo. GLP-1 was generally well tolerated. CONCLUSIONS: This study demonstrated that GLP-1 should be given continuously to obtain the most optimal glycemic control. Because of the short plasma half-life of native GLP-1, long-acting derivatives should be developed to make GLP-1 treatment clinically relevant.
In vitro fertilisation (IVF) has become a useful breeding tool in most of the developed world. In this paper the success of bovine IVF and the birth of live calves under typical South African conditions is reported. Oocytes for IVF were collected from the ovaries of 6 slaughtered Bovelder beef cows. On average, 36.2 oocytes per donor were retrieved. From these oocytes, 43 blastocysts were produced from 5 of the donors by IVF with frozen Bovelder semen. The best 11 of these embryos were transferred into oestrous, synchronised Bovelder recipients in the same herd. As a result, 7 calves were born (a 64% calving rate) from 4 of the original donors. The calves had a normal birth mass, but the mean gestation length of the male calves was significantly longer than the herd average (291.6 versus 285.2 days respectively). No calving difficulties were encountered. In summary, it was shown that IVF for bovine embryo production and transfer is possible on a commercial basis in South Africa.
To compare free beta hCG versus intact hCG in first trimester Down syndrome screening we analysed 63 cases of Down syndrome and 400 unaffected control pregnancies between 10 and 13 weeks' gestation. The Down syndrome median multiple of the median (MoM) was significantly higher (p=0.001) for free beta hCG (1.89 MoM) than for intact hCG (1.37 MoM). Although distributions for free beta hCG (unaffected, 0.2157; DS, 0.2322) are wider than for intact hCG (unaffected, 0.1697; DS, 0.2158), overall 27% of Down syndrome cases were above the 95th percentile for free beta hCG compared to 19% for intact hCG. Combined with maternal age, free beta hCG detected 45% of Down syndrome pregnancies at a 5% false positive rate. Intact hCG combined with maternal age demonstrated a detection efficiency comparable to maternal age alone (35% versus 32%). In contrast, a recent study (Haddow et al., 1998-NEJM 338: 955-961) indicated that intact hCG yielded a higher first trimester Down syndrome detection efficiency than free beta hCG (29% versus 25% respectively). Re-analysis of distribution parameters in the Haddow et al. study, however, show that free beta hCG was actually the better marker (23% detection for intact hCG versus 29% for free beta hCG).
In a consecutive and unselected series of 178 cases of carcinoma in situ of the breast (CIS), comprising both ductal (DCIS) and lobular type (LCIS), and a series of 48 cases of invasive carcinoma (IC) with predominance of DCIS, the association between histopathology, immunohistochemical markers (ER, PgR, MIB-1, c-erbB-2, and p53), and DNA ploidy was investigated, in order to discriminate biologically different groups. In DCIS, significant correlation was shown between large nuclear size and comedonecrosis, both of which showed also strong association to DNA aneuploidy, high proliferation activity, low steroid receptor content, and overexpression of c-erbB-2 and p53 factors that may indicate an aggressive behavior. Small nuclear CIS, whether LCIS or DCIS, on the contrary, were DNA diploid with low proliferation, and no cases showed overexpression of c-erbB-2 and p53. Heterogeneity with respect to the investigated parameters was also a frequent finding that may reflect a development complexity. In IC, comparison of the DCIS and the invasive component showed similar patterns. No significant differences were shown between DCIS without and with invasion. This may indicate that none of the investigated parameters on its own are essential for the event of invasion.
AIMS: The objective was to explore differences in lipid-lowering drug (LLD) prescribing in Italy and Denmark. METHODS: We used two geographical areas with computerized drug prescription records in defined populations, one in Funen, Denmark with 500 000 inhabitants, the other in Bologna, Italy with 400 000 inhabitants. Prescriptions for patients who had purchased a LLD from 1994 until 1996 were retrieved as well as coprescriptions of antidiabetic and cardiovascular drugs as markers for diabetes and cardiovascular disease. Only patients surviving and remaining in the area were included. Compliance was defined as percentage of DDDs purchased divided by the number of days within the time window. The limit between good and poor compliance was set at 82%. RESULTS: In Bologna, LLD consumption measured in DDD increased by 41% and in Funen by 129%. Annual prevalence increased from 36.9 to 46.3 users/1000 inhabitants from 1994 to 1996 and from 3.2 to 6.6 users/1000 inhabitants in Bologna and Funen, respectively. From 1995 to 1996, the incidence of use decreased slightly in Bologna from 19.3 to 18. 8/1000 inhabitants/year, whereas in Funen the incidence increased from 1.8 to 2.3/1000 inhabitants/year. In Bologna 48% and in Funen 91% of users persisted with treatment for 2 years or longer. In Bologna, 7% and in Funen 45% were good compliers. In Bologna, 61% and in Funen, 72% received other drugs indicating cardiovascular or diabetic comorbidity. CONCLUSIONS: Patterns of use differed substantially between the two areas. In contrast with Funen, where long-term use was common, Bologna LLD use was sporadic. Based on a higher rate of coprescription, LLDs seemed to be used for secondary prevention to a higher extent in Funen than in Bologna. In Funen it appeared that the correct patients, but an insufficient number of them, were being treated adequately according to guidelines. The higher discontinuation rate of lipid lowering drugs in the Bologna area indicates that a large proportion of patients use these drugs for too short a period of time to benefit from treatment. Since society's health care resources are limited it is difficult to justify public funding of these medications without at the same time giving appropriate attention to these problems.
Specific terminal carbohydrate structures and mucin-associated glycans increase in expression within the human endometrial epithelium during the secretory phase of the menstrual cycle but exhibit wide intercellular variation. We postulated that variation in glycosylation between cells would produce differences in the glycocalyx and result in complex mixtures of cells bearing different combinations of glycans. MUC-1 mucin, keratan sulphate and fucosylated lactosaminoglycans were examined in epithelial gland fragment cultures with antibodies (HMFG1, 5D4) and a lectin (Dolichos biflorus agglutinin). The glycocalyx was examined by transmission and high resolution scanning electron microscopy. The data were related to patterns of expression seen in vivo. The MUC-1 mucin was expressed relatively uniformly in culture, but heterogeneity was evident in mucin sialylation within the epithelial cell population. Double labelling of gland explant cultures for combinations of fucosylated lactosaminoglycans, keratan sulphate and MUC-1 demonstrated cells expressing all combinations of these markers. Ultrastructural examination confirmed remarkable intercellular variation in the glycocalyx. Though the human endometrial epithelium is relatively morphologically homogeneous, these observations reveal complex variations of cell surface glycosylation between neighbouring cells and suggest that secretory function might vary in a similar fashion.
PURPOSE: To provide an update of the nursing research literature on HIV infection and to develop an HIV/AIDS database using arcs computer software. METHODS: Nursing research literature from 1986 through 1997 on human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) was reviewed. With an emphasis on client-focused research, 246 studies were entered into the arcs HIV/AIDS database. FINDINGS: Analysis of over 1,000 citations in the HIV/AIDS nursing research literature over the past decade indicated that 22% (n = 219) of the nursing studies were client- or patient-focused; 29% (n = 292) were risk-group focused; and 49% (n = 492) were provider-focused. Of the 246 studies entered into the arcs HIV/AIDS database, 88 (35.7%) were classified in the psychologic domain, 65 (26.4%) in the physiologic domain, 24 (9.7%) in the behavioral domain, and 25 (10%) in the social domain. In addition, 17 (6.9%) of the studies were classified in the quality of life domain, and 27 (10.9%) in the stage of HIV disease domain. The majority (53%) of the 246 studies (n = 131) were correlational, 86 (35%) were descriptive, and 29 (12%) had experimental or quasi-experimental designs. CONCLUSIONS: Although nursing studies have described some of the problems that affect HIV-infected people, further research is needed, particularly related to clinical interventions.
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This case details a patient with primary amenorrhea with an unusual cause. She presented at age 16 with short stature, minimal sexual development and no prior menses. Her history was significant for poorly controlled type 1 diabetes. She had been evaluated previously for growth hormone deficiency, and had received a short course of growth hormone therapy. Of greatest significance was the fact that she had also had a decreased sense of smell since her youth. Although a previous computerized tomography scan had been reported as normal, follow-up magnetic resonance imaging demonstrated the absence of olfactory bulbs. Smell testing confirmed the absence of smell and testing of gonadotropin releasing hormone demonstrated an inadequate response. All of these features suggested Kallmann syndrome. This syndrome commonly presents with delayed onset of puberty and decreased or absent sense of smell. There are also many associated features, and the disease is remarkable for its great genotypic and phenotypic variability. Current understanding of its pathogenesis, the commonly associated features of Kallmann syndrome and the impact of diabetes on growth and sexual development are reviewed.
The paper presents as an example the types of mathematical models that are used in a full scale anesthesia simulator. The models vary from detailed reference models, based on fundamental physiological laws and principles, to simple script based models. A few considerations on the implementation of the models are also given.
Potent and orally bioavailable nonthiol-containing inhibitors of protein farnesyltransferase are described. Oral bioavailability was achieved by replacement of the pyridyl ether moiety of 1 with a 2-substituted furan ether to give 4. Potency was regained with 2,5-disubstituted furan ethers while maintaining the bioavailability inherent in 4. p-Chlorophenylfuran ether 24 is 0.7 nM in vitro (FTase) and is 32% bioavailable in the mouse, 30% bioavailable in rats, and 21% bioavailable in dogs.