Governance, Accountability, and Organizational Development: Eldercare Unit Managers' and Local Politicians' Experiences of and Responses to State Supervision of Swedish Eldercare.

This article explores how local politicians and care unit managers in Swedish eldercare experience and respond to state supervision (SSV). Twelve politicians and twelve managers in 15 previously inspected municipalities were interviewed about their experiences of and reactions to SSV in relation to their views of care quality and routines in eldercare practice. The findings indicate that local managers and political chairs perceived SSV in eldercare positively at a superficial level but were critical of and disappointed with specific aspects of it. In terms of (a) governance, chairs and managers said SSV strengthened implementation of national policies via local actors, but they were critical of SSV's narrow focus on control and flaws in eldercare practice. With regard to (b) accountability, SSV was seen as limited to accountability for finances and systemic performance, and regarding (c) organizational development, SSV was seen as limited to improving routines and compliance with legislation, while local definitions of quality are broader than that. In general, local actors regarded SSV as improving administrative aspects and routines in practice but ignoring the relational content of eldercare quality.

Growing as a Human Being--Obese Adolescents' Experiences of the Changing Body.

The aim of the presented study was to describe how obese adolescents experience themselves and their bodies and how their views changed as a result of participation in a weight loss program. A total of five adolescents were interviewed in this qualitative study. Data were analyzed by means of content analysis. One main theme emerged, "Growing as a human being", which comprised four themes based on 13 sub-themes. Being part of a weight loss program was a time of transition that led not only to weight reduction but also to a higher level of well-being and a feeling of dignity.

Small amounts of involuntary muscle activity reduce passive joint range of motion.

When assessing passive joint range of motion in neurological conditions, concomitant involuntary muscle activity is generally regarded small enough to ignore. This assumption is untested. If false, many clinical and laboratory studies that rely on these assessments may be in error. We determined to what extent small amounts of involuntary muscle activity limit passive range of motion in 30 able-bodied adults. Subjects were seated with the knee flexed 90° and the ankle in neutral, and predicted maximal plantarflexion torque was determined using twitch interpolation. Next, with the knee flexed 90° or fully extended, the soleus muscle was continuously electrically stimulated to generate 1, 2.5, 5, 7.5, and 10% of predicted maximal torque, in random order, while the ankle was passively dorsiflexed to a torque of 9 N·m by a blinded investigator. A trial without stimulation was also performed. Ankle dorsiflexion torque-angle curves were obtained at each percent of predicted maximal torque. On average (mean, 95% confidence interval), each 1% increase in plantarflexion torque decreases ankle range of motion by 2.4° (2.0 to 2.7°; knee flexed 90°) and 2.3° (2.0 to 2.5°; knee fully extended). Thus 5% of involuntary plantarflexion torque, the amount usually considered small enough to ignore, decreases dorsiflexion range of motion by ~12°. Our results indicate that even small amounts of involuntary muscle activity will bias measures of passive range and hinder the differential diagnosis and treatment of neural and nonneural mechanisms of contracture. NEW & NOTEWORTHY The soleus muscle in able-bodied adults was tetanically stimulated while the ankle was passively dorsiflexed. Each 1% increase in involuntary plantarflexion torque at the ankle decreases the range of passive movement into dorsiflexion by >2°. Thus the range of ankle dorsiflexion decreases by ~12° when involuntary plantarflexion torque is 5% of maximum, a torque that is usually ignored. Thus very small amounts of involuntary muscle activity substantially limit passive joint range of motion.

Low daily 10-mg and 20-mg doses of fluvoxamine inhibit the metabolism of both caffeine (cytochrome P4501A2) and omeprazole (cytochrome P4502C19).

OBJECTIVES: Fluvoxamine is metabolized by the polymorphic cytochrome P450 (CYP) 2D6 and the smoking-inducible CYP1A2. Therapeutic doses of fluvoxamine inhibit both CYP1A2 and CYP2C19. In this study we used extensive metabolizers (EMs) and poor metabolizers (PMs) of debrisoquin (INN, debrisoquine) (CYP2D6) and two probes, caffeine (CYP1A2) and omeprazole (CYP2C19), to investigate whether nontherapeutic doses of fluvoxamine inhibit CYP1A2 but possibly not CYP2C19. METHODS: Single oral doses of 100 mg caffeine and 20 mg omeprazole were given separately to 5 EMs and 5 PMs of debrisoquin to assess the activity of CYP1A2 and CYP2C19, respectively. Initially, a single oral dose of fluvoxamine (25 mg to PMs and 50 mg to EMs) was given, followed by 1 week of daily administration of 25 mg x 2 to EMs and 25 mg x 1 to PMs. Caffeine (day 6) and omeprazole (day 7) were again administered at the steady state of fluvoxamine. Later the study protocol was repeated with a lower dose of fluvoxamine, 10 mg x 2 to EMs and 10 mg x 1 to PMs for 1 week. Concentrations of fluvoxamine, caffeine, omeprazole, and their metabolites were analyzed by HPLC methods in plasma and urine. RESULTS: The kinetics of fluvoxamine were not significantly different in EMs and PMs after a single oral dose of the drug. At the higher but not the lower steady-state dose of fluvoxamine, a significantly lower clearance in PMs compared with EMs was observed (geometric mean, 0.86 versus 1.4 L/h per kilogram; P <.05). At steady state, the 25 mg x 1 or x 2 fluvoxamine dose caused a pronounced inhibition of about 75% to 80% for both CYP1A2 and CYP2C19, whereas the inhibition after the lower 10 mg x 1 or x 2 dose was about 40% to 50%. The area under the plasma concentration-versus-time curve from 0 to 24 hours [AUC(0-24)] of caffeine increased 5-fold (P <.001) after the higher dose of fluvoxamine and 2-fold (P <.05) after the lower dose. The area under the plasma concentration-time curve from time zero to 8 hours [AUC(0-8)] ratio of 5-hydroxyomeprazole/omeprazole decreased 3.4-fold (P <.001) and 2.4-fold (P <.001), respectively. One EM subject had a very low oral clearance of fluvoxamine after both single and multiple dosing of the drug. This subject might have a deficient transporter protein in the gut, leading to an increased absorption of fluvoxamine. CONCLUSION: No convincing evidence was found that CYP2D6 is an important enzyme for the disposition of fluvoxamine. Other factors seem to be more important. A nontherapeutic oral daily dose of fluvoxamine is sufficient to provide a marked inhibition of both caffeine (CYP1A2) and omeprazole (CYP2C19) metabolism. It was not possible to separate the inhibitory effects of fluvoxamine on these enzymes, even after such a low daily dose such as 10 mg x 1 or x 2 of fluvoxamine.

The Karolinska cocktail for phenotyping of five human cytochrome P450 enzymes.

OBJECTIVES: Our objectives were (1) to determine whether the drugs caffeine, losartan, omeprazole, debrisoquin (INN, debrisoquine), and quinine can be given simultaneously in low doses as a cocktail for the phenotyping of cytochrome P450 (CYP) 1A2, 2C9, 2C19, 2D6, and 3A4, respectively, and (2) to design an administration schedule to give as few sampling occasions as possible. METHODS: Twenty-four subjects were given oral doses of 100 mg caffeine, 25 mg losartan, 20 mg omeprazole, 10 mg debrisoquin, and 250 mg quinine on separate days. After a washout period of at least 4 days, all drugs were given simultaneously except for quinine, which was given 8 hours after the other drugs. Blood and urine samples were collected to determine parent drug and metabolite concentrations for assessment of phenotyping indices. Any difference between both single and cocktail doses was tested on a log-normal distribution. RESULTS: The phenotypic indices of CYP1A2 (paraxanthine/caffeine in 4-hour plasma), CYP2C9 (losartan/E-3174 [metabolite of losartan] in 0- to 8-hour urine), CYP2C19 (omeprazole/5-hydroxyomeprazole in 3-hour plasma), and CYP3A4 (quinine/3-hydroxyquinine in 16-hour plasma) were not significantly changed when probe drugs were administered alone compared with together, although a tendency toward higher concentrations of losartan was seen during simultaneous administration (95% confidence interval, 0.51-1.002; P =.051). The CYP2D6 phenotypic index (debrisoquin/4-hydroxydebrisoquin in 0- to 8-hour urine) was significantly changed when drugs were given together (95% confidence interval, 0.45-0.87; P =.007), indicating an inhibition of the debrisoquin metabolism. The within-subject coefficients of variation (8%-25%) were much lower than the between-subject coefficients of variation (34%-79%). CONCLUSIONS: The administration of drugs together suggests an inhibition of debrisoquin metabolism caused by the concurrent drugs given. By separating debrisoquin from the other cocktail drugs, this method is likely to be used as a tool to phenotype the enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 with only 2 urinary collections and 2 blood-sampling occasions.

Principles for derivation of human embryonic stem cells.

This chapter describes the principles for derivation and maintenance of human embryonic stem cells. Detailed protocols are outlined and researchers who are generally skilled in mammalian cell culture should be able to repeat the processes successfully. Further, the protocols are intended for scientists who do not have access to advanced IVF equipment and therefore cannot perform, e.g. assisted hatching. In addition to derivation, we also discuss characterisation and banking of hES cells.

Measuring possible effect on health-related quality of life by tactile massage or relaxation in patients with type 2 diabetes.

OBJECTIVE: The aim was to study the effect of tactile massage versus relaxation exercises on health-related quality of life (HRQoL) in patients with type 2 diabetes, at primary-health-care centres in Stockholm county. DESIGN: The study was carried out as a parallel-arm clinical trial. Patients with type 2 diabetes and HbA1c of 6-8%, aged 35-75, with oral anti-diabetic treatment were included. In all, 26 and 27 attendants in the TM and relaxation group, respectively, entered the study and were included in the intention-to-treat analysis. The attendants were offered one weekly session of TM or the use of relaxation exercises at least once weekly for a total of 10 weeks. MAIN OUTCOME MEASURES: HRQoL was measured using the SF-36 questionnaire at baseline, after 10 weeks of therapy and 3 months after the completion of the study. Owing to multiple comparisons the level of statistical significance was set at p<0.01, and values of p>0.01 and <0.05 were regarded as borderline values. RESULTS: One difference over time between the groups was reaching a borderline value in favour of the relaxation group, i.e. the scale of "Role functioning, physical" (p<0.05). CONCLUSIONS: Based on the findings in this study, we conclude that stress-relieving techniques with TM or relaxation CD have limited, if any, beneficial effects on health-related quality of life in Swedish-born patients with type 2 diabetes. We cannot, however, rule out that specific patient groups with higher levels of perceived stress could show benefits with this kind of treatment.

Tactile massage within the primary health care setting.

UNLABELLED: This paper describes an observational study describing how Tactile Massage (TM) was integrated into Swedish clinical medical care, the impact of this initiative suggests a foundation for future research. Subjects completed three questionnaires pre- and post-tactile massage. These were: Sense of Coherence (SOC), an enlarged Health Index (HI) and the Borg CR10 scale. RESULTS: A convenience sample of forty-three subjects (37 women and 6 men) were referred to TM treatment for a range of problems including for pain, sleep disorders, inability to move, headache and tense body. Patients received 10 TM treatments, each lasting approx. 1h in length. The enlarged HI questionnaire indicated that eleven out of fourteen parameters were significantly affected according (p-values between 0.0015 and <0.001). These included energy, mood, tiredness, sleep, pain, movement, health, general health and physical health. Pain reduction was also significantly reduced using the Borg CR10 scale (p<0.001). CONCLUSION: TM seems to affect several dimensions of health, and this should be explored more fully in future research.

Blood group ABO antigen expression in human embryonic stem cells and in differentiated hepatocyte- and cardiomyocyte-like cells.

BACKGROUND: The use of stem cells in regenerative medicine and transplantation may require grafting of cells that will challenge the recipient's immune system. Our knowledge of tissue antigen expression in human embryonic stem cells (hESC) and during their differentiation is limited, especially regarding histo-blood group AB(O)H antigens. METHODS: Nine different hESC lines, and hESC-derived hepatocyte- and cardiomyocyte-like cells, were blood group ABO genotyped and A/B antigen expression was studied by immunohistochemistry. RESULTS: This study reveals, for the first time, that A and B antigens in hESC were expressed according to the ABO genotype and that the antigens had a different cellular/sub-cellular distribution. In addition, several genotype A hESC lines stained positive with one anti-B antibody. Furthermore, studies of hepatocyte- and cardiomyocyte-like cells of different maturation state, originating from a blood group B hESC line, showed that hepatocyte-like cells expressed B antigens whereas cardiomyocyte-like cells were negative. CONCLUSION: Since clinical stem-cell therapy is likely to be performed with immature progenitor cells, blood group ABO compatibility of donor cells/recipients should be favorable to avoid unnecessary rejection problems caused by ABO incompatibility. The in vitro loss of B antigens in a genotype B hESC line indicates that loss of ABH antigens occurs early during human embryogenesis since these antigens are lacking in adult cardiomyocytes.

Derivation of a xeno-free human embryonic stem cell line.

Elimination of all animal material during both the derivation and long-term culture of human embryonic stem cells (hESCs) is necessary prior to future application of hESCs in clinical cell therapy. The potential consequences of transplanting xeno-contaminated hESCs into patients, such as an increased risk of graft rejection [Stem Cells 2006; 24:221-229] and the potential transfer of nonhuman pathogens, make existing hESC lines unsuitable for clinical applications. To avoid xeno-contamination during derivation and culture of hESCs, we first developed a xeno-free medium supplemented with human serum, which supports long-term (>50 passages) culture of hESCs in an undifferentiated state. To enable derivation of new xeno-free hESCs, we also established xeno-free human foreskin fibroblast feeders and replaced immunosurgery, which involves the use of guinea pig complement, with a modified animal-product-free derivation procedure. Here, we report the establishment and characterization (>20 passages) of a xeno-free pluripotent diploid normal hESC line, SA611.

High-resolution analysis of the subtelomeric regions of human embryonic stem cells.

The use of human embryonic stem cells (hESCs) in most applications is dependent on their undifferentiated proliferation in vitro. Recent studies have illustrated the possibility that chromosomal changes may occur in hESCs during in vitro propagation of these cells. However, no studies so far have screened for chromosomal abnormalities in hESCs using high-resolution techniques that can detect alterations on a few base-pair levels. We have used the recently developed multiplex ligation-dependent probe amplification procedure to analyze the possible occurrence of deletions or duplications in the subtelomeric regions of hESCs in early and late passages. In this study we show that no subtelomeric anomalies were detected in any of the nine hESC lines investigated, supporting the conclusion that hESCs, under appropriate conditions, maintain genomic stability during in vitro propagation.

Frostbite injuries treated in the Helsinki area from 1995 to 2002.

BACKGROUND: : Exposure to cold results in frostbite, superficial or deeper tissue damage. In severe frostbites, amputations are life-saving but diminish quality of life (QOL). METHODS: : Retrospective study was performed. RAND 36- questionnaire was administered to assess QOL. Our aim was to investigate risk factors and adjustment to everyday life of hospitalized patients. RESULTS: : 92 frostbites in 42 patients were recorded. One third of the patients were chronic alcoholics. Age and temperature were statistically significant factors for unfavorable outcome. 20% of patients required secondary reconstructive procedures. One-third reported their emotional well-being very poor. Half had limitations in social life. CONCLUSIONS: : Hospitalized cases of frostbite are rare. Anti-social behavior increases the risk in general, and patients present with complicated problems similar to those encountered in burns victims. We recommend that frostbite patients requiring hospital attendance are treated in specialized units, where sufficient expertise for acute as well as reconstructive surgery is available.

Human blastocysts for the development of embryonic stem cells.

Establishment of human embryonic stem cells (hES) from surplus human IVF embryos has been successful when both fresh and frozen-thawed cleavage stage embryos have been cultured to the blastocyst stage. This study reports the characteristics of the starting material, the blastocysts, for hES cell lines that were first derived at the University of Gothenburg, Sahlgrenska University Hospital in 1999. Twenty-two hES cell lines were derived by Cellartis AB from 114 blastocysts, giving an overall success rate of 19.3%. The blastocysts from which the hES cell lines were established were of varying morphological quality, both fresh and frozen-thawed. Two techniques of hES establishment were applied, i.e. direct application of the blastocysts on feeder cells or the standard immunosurgery method. It was further found that the efficiency by which frozen-thawed embryos gave rise to new hES cell lines was 3.7 times better than with fresh surplus embryos. These findings suggest that frozen-thawed embryos are superior to fresh surplus human embryos in hES cell establishment, which also avoids specific ethical problems associated with embryo donation in a fresh IVF cycle.