Borderline personality disorder and the diagnostic co-occurrence of mental health disorders and somatic diseases: A controlled prospective national register-based study.

OBJECTIVE: Information on borderline personality disorder (BPD) and its comorbidities is often limited to concentrate on a few diagnoses. The aim of the study was to use national register data to investigate all diagnostic co-occurring mental health disorders and somatic diseases 3 years before and after initial BPD diagnosis compared with a matched control group. METHOD: The study was a register-based cohort of 2756 patients with incident BPD (ICD F60.3) and 11,024 matched controls, during 2002-2016. Comorbidity data were classified into main disease groups, in accordance with the World Health Organization ICD-10 criteria. RESULTS: Almost half the patients had been diagnosed with mental and behavioral disorders before the BPD diagnosis as compared to 3% in the control group. Further, the co-occurrence of diseases due to external causes of morbidity, including injury, self-harm, and poisoning were more represented in the BPD group before diagnosis as compared to the control group. In addition, co-occurring morbidity related to diseases in the circulatory, the respiratory, the digestive, the musculoskeletal, and the genitourinary system was more represented in the BPD group. After diagnosis, the proportion of patients with co-occurring morbidity increased further in all main disease groups in the BPD group. As many as 87% of patients had mental and behavioral co-occurring morbidity and 15% nervous diseases as compared with 3% and 4%, respectively, in the control group. Also, comorbidities related to external causes of morbidity, including for example, injury and self-harm were more represented in the BPD group. The BPD group had more somatic co-occurring morbidity, especially digestive, respiratory, circulatory, and endocrine diseases. Finally, the mortality over 12 years was statistically significantly higher in people with BPD than in the control group. CONCLUSION: Patients with BPD have higher odds for multiple physical health conditions and co-occurrence of mental health disorders.

Healthcare cost variation in patients with heart failure: a nationwide study.

OBJECTIVE: Heart failure (HF) imposes a major economic burden; however, the individual management for patients varies, potentially leading to large cost heterogeneity. The aim of this study was to investigate the spectrum of health cost by patients with HF and factors associated with high direct health cost. STUDY DESIGN: This was a nationwide, retrospective longitudinal study. METHODS: Using Danish nationwide registries from 2012 to 2015, we identified all patients aged >18 years with a first-time diagnosis of HF. Total health costs were investigated using two perspectives-at index and during 3 years of follow-up. Patients were investigated by decile cost groups. A multivariable logistic regression was used to identify variables associated with being in the highest cost decile compared with the rest (90%). RESULTS: A total of 11,170 patients with HF were included, and those in the highest cost decile (n = 1117, 10%) were younger (69 vs. 75 years), fewer were females (34% vs. 43%), and more were inpatients (83% vs. 70%) compared with the rest of the patients with HF (n = 10,053, 90%). Patients in the highest cost decile (10%) incurred a 30 times higher cost with a mean total health cost in index year of €86,607 compared with €2893 for patients in lowest cost decile (10%). The results were similar for 3 years aggregated (€139,473 vs. €4086), corresponding to a 34 times higher cost. CONCLUSION: In patients with HF, a large total health cost heterogeneity exists with younger age, inpatient admittance, male sex, and comorbidities being associated with a higher likelihood of belonging to the highest cost group.

Cost-effectiveness of 12 weeks of supervised treatment compared to written advice in patients with knee osteoarthritis: a secondary analysis of the 2-year outcome from a randomized trial.

OBJECTIVE: To assess the 24-month cost-effectiveness of supervised treatment compared to written advice in knee osteoarthritis (OA). DESIGN: 100 adults with moderate-severe OA not eligible for total knee replacement (TKR) randomized to a 12-week individualized, supervised treatment (exercise, education, diet, insoles and pain medication) or written advice. Effectiveness was measured as change in quality-adjusted life years (QALYs) from baseline to 24 months, including data from baseline, 3, 6, 12 and 24 months, while healthcare costs and transfer payments were derived from national registries after final follow-up. Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. A sensitivity analysis resampling existing data was conducted and the probability of cost-effectiveness was estimated using a 22,665 Euros/QALY threshold. In a sensitivity analysis, cost-effectiveness was calculated for different costs of the supervised treatment (actual cost in study; cost in private practice; and in-between cost). RESULTS: Average costs were similar between groups (6,758 Euros vs 6,880 Euros), while the supervised treatment were close to being more effective (incremental effect (95% CI) of 0.075 (-0.005 to 0.156). In the primary analysis excluding deaths, this led the supervised treatment to be cost-effective, compared to written advice. The sensitivity analysis demonstrated that the results were sensitive to changes in the cost of treatment, but in all scenarios the supervised treatment was cost-effective (ICERs of 6,229 to 20,688 Euros/QALY). CONCLUSIONS: From a 24-month perspective, a 12-week individualized, supervised treatment program is cost-effective compared to written advice in patients with moderate-severe knee OA not eligible for TKR. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01535001.

Cause-specific mortality in patients with psoriasis and psoriatic arthritis.

BACKGROUND: There are limited data regarding causes of mortality in patients with psoriasis or psoriatic arthritis (PsA). OBJECTIVES: This retrospective cohort study evaluated the risk and leading causes of mortality in patients with psoriasis or PsA. METHODS: Individuals with a hospital-based diagnosis of PsA or psoriasis were identified using the Danish National Patient Registry. Matched control individuals were identified from the general population. The main outcome measures were risk of death and cause-specific mortality in patients with psoriasis or PsA. RESULTS: Death rates per 1000 patient-years (with 95% confidence intervals) vs. controls were 22·3 (19·7-24·9) vs. 13·9 (11·8-16·0) for patients with psoriasis and 10·8 (8·9-12·8) vs. 11·6 (9·6-13·6) for patients with PsA. Survival, according to stratified hazard ratios (HRs), was significantly lower in patients with psoriasis than in controls (HR 1·74, P < 0·001), but not in patients with PsA (HR 1·06, P = 0·19). Significantly increased risk of death was observed in patients with psoriasis vs. controls due to a number of causes; the highest risks were observed for diseases of the digestive system; endocrine, nutritional and metabolic diseases; and certain infectious and parasitic diseases (HRs 3·61, 3·02 and 2·71, respectively). In patients with PsA, increased mortality was observed only for certain infectious and parasitic diseases (HR 2·80) and diseases of the respiratory system (HR 1·46). Patients with psoriasis died at a younger age than controls (mean age 71·0 vs. 74·5 years, P < 0·001). CONCLUSIONS: Patients with severe psoriasis have increased mortality risk compared with matched controls, due to a number of causes. Evidence to support an increased risk for patients with PsA was less convincing.

Societal costs of Borderline Personality Disorders: a matched-controlled nationwide study of patients and spouses.

OBJECTIVE: Information on societal cost of patients with Borderline Personality Disorder (BPD) and spouses is limited. The aim was to investigate factual societal costs before and after initial BPD diagnosis. METHOD: A register-based cohort study of 2756 patients with incident BPD (ICD F60.3) with spouses and 11 024 matched controls, during 2002-2016. RESULTS: Total direct healthcare costs and lost productivity costs amounted €40 441 for patients with BPD, which was more than 16 times higher than the matched controls. Somatic and psychiatric health care costs and costs of lost productivity were increased during 5 years before initial diagnosis of BPD. Before and after initial diagnosis, health care costs and lost productivity were increased among spouses of patients with BPD. CONCLUSION: Patients with BPD differed substantially from the general population with respect to all included costs. The study documented a significant burden on their spouses. Besides the early onset of BPD, which implies that patients are affected before they finish school and enter labor market, the neurocognitive impairment and fundamental symptoms of BPD, e.g. unstable, intense relationships, impulsivity, and lack of stable sense of self together with psychiatric and somatic comorbidity are part of explanation of the excess costs of BPD.

Morbidity and mortality following poliomyelitis - a lifelong follow-up.

BACKGROUND AND PURPOSE: In the world today 10-20 million people are still living with late effects of poliomyelitis (PM), but the long-term consequences of the disease are not well known. The aim of this study was to describe lifelong morbidity and mortality among Danes who survived PM. METHODS: Data from official registers for a cohort of 3606 Danes hospitalized for PM in the period 1940-1954 were compared with 13 762 age- and gender-matched controls. RESULTS: Compared with controls, mortality was moderately increased for both paralytic as well as non-paralytic PM cases; Hazard Ratio, 1.31 (95% confidence interval, 1.18-1.44) and 1.09 (95% confidence interval, 1.00-1.19), respectively. Hospitalization rates were approximately 1.5 times higher among both paralytic and non-paralytic PM cases as compared with controls. Discharge diagnoses showed a broad spectrum of diseases. There were no major differences in morbidities between paralytic and non-paralytic PM cases. CONCLUSIONS: Poliomyelitis has significant long-term consequences on morbidity and mortality of both paralytic and non-paralytic cases.

The cost-utility of sodium oxybate as narcolepsy treatment.

AIMS AND OBJECTIVES: Based on class-I studies, sodium oxybate is regarded as a first-line treatment for both EDS and cataplexy. The cost-effectiveness of sodium oxybate is largely unknown, though. In this study, we estimate the cost-effectiveness of sodium oxybate as treatment for patients with narcolepsy as compared to standard treatment, by calculating incremental cost-effectiveness ratios (cost per quality-adjusted life year, QALY) for patients in a Swedish setting. MATERIALS AND METHODS: Calculations were performed using a Markov model with a 10-year time horizon. The study population consisted of adult patients treated for narcolepsy with cataplexy. Healthcare utilization and quality-adjusted life years (QALYs) for each treatment alternative were calculated assuming no treatment effect on survival. Sensitivity analyses were performed for treatment effectiveness and healthcare cost parameters. RESULTS: The cost per additional quality-adjusted life year was estimated at SEK 563,481. The cost-effectiveness measure was demonstrated to be particularly sensitive to the duration of the relative quality-of-life improvements accruing to patients treated with sodium oxybate. CONCLUSIONS: The estimated cost per additional QALY for the sodium oxybate treatment alternative compared with standard treatment was estimated above the informal Swedish willingness-to-pay threshold (SEK 500,000). The estimated cost per additional QALY obtained here is likely to overestimate the true cost-effectiveness ratio as potentially beneficial effects on productivity of treatment with sodium oxybate were not included (due to lack of data).

Cost and health care resource use associated with noncompliance with oral bisphosphonate therapy: an analysis using Danish health registries.

We estimated the rate of compliance with oral bisphosphonates among Danish women and examined its association with health care resource use and cost. Approximately 30 % of Danish females aged >55 who take bisphosphonates are noncompliant, and noncompliance is significantly associated with increased health care resource use and cost. INTRODUCTION: Two objectives of this study were to estimate the rate of oral bisphosphonate compliance among Danish women and to examine the association of noncompliance with health care resource use and cost. METHODS: Women ≥55 with an index prescription claim for an oral bisphosphonate were identified from Danish national health registries between 2003 and 2008. Compliance was measured as the medication possession ratio (MPR) during the first 12 months post-index. Cost and health care resource use were collected for the following 12 months. RESULTS: Among the 38,234 women meeting the study inclusion criteria, 29.9 % were noncompliant (MPR <70 %). Younger age was associated with higher odds of compliance (OR [95 % CI] 1.22 [1.15-1.29] for ages 55-64 and 1.18 [1.12-1.24] for ages 65-74; reference age group ≥75 years). Rates of all-cause health care resource use were significantly higher in noncompliant subjects: 28.9 versus 23.0 % had inpatient admissions, 16.5 versus 13.0 % had emergency room visits, and 48.7 versus 43.3 % used outpatient services (P < 0.001 for all comparisons). The total mean (SD) all-cause cost per patient (excluding office visits) was €626 (2344) and €4178 (7854), respectively. The mean (SD) osteoporosis-related cost per patient (excluding office visits) was €572 (2085) and €754 (2857) for compliant and non-compliant subjects, respectively. The compliant subjects accrued significantly lower all-cause and OP-related cost than noncompliant subjects, regardless of whether the total cost or medical cost only was considered. CONCLUSIONS: Approximately 30 % of Danish females aged 55 or older who take bisphosphonates are noncompliant. Noncompliance is significantly associated with increased health care resource use and cost.

Health, social and economic consequences of dementias: a comparative national cohort study.

BACKGROUND AND PURPOSE: Dementia causes morbidity, disability and mortality, and as the population ages the societal burden will grow. The direct health costs and indirect costs of lost productivity and social welfare of dementia were estimated compared with matched controls in a national register based cohort study. METHODS: Using records from the Danish National Patient Registry (1997-2009) all patients with a diagnosis of Alzheimer's disease, vascular dementia or dementia not otherwise specified and their partners were identified and compared with randomly chosen controls matched for age, gender, geographical area and civil status. Direct health costs included primary and secondary sector contacts, medical procedures and medication. Indirect costs included the effect on labor supply. All cost data were extracted from national databases. The entire cohort was followed for the entire period - before and after diagnosis. RESULTS: In all, 78 715 patients were identified and compared with 312 813 matched controls. Patients' partners were also identified and matched with a control group. Patients had lower income and higher mortality and morbidity rates and greater use of medication. Social- and health-related vulnerability was identified years prior to diagnosis. The average annual additional cost of direct healthcare costs and lost productivity in the years before diagnosis was 2082 euros per patient over and above that of matched controls, and 4544 euros per patient after the time of diagnosis. CONCLUSIONS: Dementias cause significant morbidity and mortality, consequently generating significant socioeconomic costs.

The socioeconomic consequences of optic neuritis with and without multiple sclerosis: a controlled national study.

OBJECTIVES: Optic neuritis (ON) often precedes multiple sclerosis (MS). MS is associated with a significant socioeconomic burden. However, the burden of ON with and without MS before and after its diagnosis has never been calculated. METHODS: Using complete national records from the Danish National Patient Registry (1998-2006), we identified 1677 patients with ON and compared them with 6708 randomly selected citizens matched for age, sex and geography. A societal perspective is taken towards the cost analyses. Costs included in the analysis are those of the health sector, including all contacts with primary and secondary sectors, and the use and costs of drugs. Productivity losses included labour supply and income. All social transfer payments were also calculated. RESULTS: Patients with ON had higher rates of contact with healthcare services, medication use and income from employment, all of which incurred a higher socioeconomic cost. Employed patients had lower income than control subjects. The total annual excess costs relative to matched controls were €3501 for ON patients and €9215 for patients with a dual diagnosis of ON and MS. The ON and ON+MS patients received an annual mean excess social transfer income of €1175 and €4619. ON/ON+MS patients presented social and economic consequences up to 8 years before diagnosis, and these increased after the diagnosis was established. CONCLUSIONS: ON, especially if combined with a diagnosis of MS, has a significant socioeconomic consequence for the individual patient and for society. Productivity losses are a far more important economic factor than health sector costs.

The SOFIA pilot trial: a cluster-randomized trial of coordinated, co-produced care to reduce mortality and improve quality of life in people with severe mental illness in the general practice setting.

BACKGROUND: People with severe mental illness (SMI) have an increased risk of premature mortality, predominantly due to somatic health conditions. Evidence indicates that primary and tertiary prevention and improved treatment of somatic conditions in patients with SMI could reduce this excess mortality. This paper reports a protocol designed to evaluate the feasibility of a coordinated co-produced care program (SOFIA model, a Danish acronym for Severe Mental Illness and Physical Health in General Practice) in the general practice setting to reduce mortality and improve quality of life in patients with severe mental illness. METHODS: The SOFIA pilot trial is designed as a cluster randomized controlled trial targeting general practices in two regions in Denmark. We aim to include 12 practices, each of which is instructed to recruit up to 15 community-dwelling patients aged 18 and older with SMI. Practices will be randomized by a computer in a ratio of 2:1 to deliver a coordinated care program or usual care during a 6-month study period. A randomized algorithm is used to perform randomization. The coordinated care program includes educational training of general practitioners and their clinical staff educational training of general practitioners and their clinical staff, which covers clinical and diagnostic management and focus on patient-centered care of this patient group, after which general practitioners will provide a prolonged consultation focusing on individual needs and preferences of the patient with SMI and a follow-up plan if indicated. The outcomes will be parameters of the feasibility of the intervention and trial methods and will be assessed quantitatively and qualitatively. Assessments of the outcome parameters will be administered at baseline, throughout, and at end of the study period. DISCUSSION: If necessary the intervention will be revised based on results from this study. If delivery of the intervention, either in its current form or after revision, is considered feasible, a future, definitive trial to determine the effectiveness of the intervention in reducing mortality and improving quality of life in patients with SMI can take place. Successful implementation of the intervention would imply preliminary promise for addressing health inequities in patients with SMI. TRIAL REGISTRATION: The trial was registered in Clinical Trials as of November 5, 2020, with registration number NCT04618250 . Protocol version: January 22, 2021; original version.

The socio-economical burden of hypersomnia.

OBJECTIVES: In the absence of socio-economical consequences of hypersomnia this study addresses the factual indirect and direct costs. METHODS: Two thousand two hundred and eight patients with a hypersomnia diagnosis from 1998 to 2005 were identified in the Danish national patient registry (NPR), each compared with 4 age and gender adjusted, randomly chosen citizens selected from the Civil Registration System Statistics. The health cost was decomposed in direct and indirect yearly costs, including labor supply and social transfer payments. Direct costs included frequencies and costs of discharges and outpatient use by cost weights according to diagnosis related groups and specific outpatient prices based on data from The Danish Ministry of Health. The use of and costs of drugs was based on data from the Danish Medicines Agency. The frequencies and costs from primary sectors were based on data from The National Health Security. Indirect costs were based on income data from the coherent social statistics (CSS). RESULTS: Patients with hypersomnia presented significant higher health related contact rate, expenses and medication use. No differences were identified in employment and income. The yearly sum of direct and indirect costs were yearly euro3402 vs. euro1212 in controls (P < 0.001), corresponding to a yearly excess costs euro2190. The patients presented higher transfer income, total euro889. CONCLUSION: Hypersomnia patient present higher health and medication uses, and social transfer income and thus represent a significant socio-economical burden.

Increased socioeconomic burden in patients with primary progressive multiple sclerosis: A Danish nationwide population-based study.

BACKGROUND: Primary progressive multiple sclerosis (PPMS) is characterized by development of more chronic neurological manifestations from disease onset compared with relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) but the following socioeconomic consequences have never been described in a nation-wide patient population. OBJECTIVE: To determine if socioeconomic burden of PPMS is increased compared with RRMS and SPMS. METHODS: We included patients from The Danish Multiple Sclerosis Registry diagnosed between 1998 and 2015. Yearly average health costs, public transfers and earned income was calculated from the index diagnosis date, and each year in a five-year period before and after index diagnosis date, for the three patient groups. A regression model estimating the odds ratio (OR) with PPMS as the comparator, was used to analyze the differences between PPMS vs. RRMS and PPMS vs. SPMS controlling for age and sex. RESULTS: In total, 9563 MS patients were identified (1998-2015), with a characteristic distribution between different disease courses: 7012 patients with RRMS (73%), 1099 patients with PPMS (11%) and 1452 patients with SPMS (15%). Total health costs were lower in RRMS vs. PPMS (OR 0.76; 95% CI 0.74-0.78; p<0.0001) but not in SPMS vs. PPMS (OR 1.06; 95% CI 1.03-1.09; p<0.0001). Especially homecare costs were lower in RRMS vs. PPMS (OR 0.17; 95% CI 0.17-0.18; p<0.0001), less pronounced in SPMS vs. PPMS (OR 0.93; 95% CI 0.90-0.97; p = 0.0001). OR for health costs before and after diagnosis was significantly lower in RRMS vs. PPMS regarding most variables, less pronounced in SPMS vs. PPMS. CONCLUSION: This nation-wide population-based study show that socioeconomic burden is significantly higher in PPMS relative to RRMS, but less pronounced compared with SPMS.

LysoPC acyltransferase/PC transacylase activities in plant plasma membrane and plasma membrane-associated endoplasmic reticulum.

BACKGROUND: The phospholipids of the plant plasma membrane are synthesized in the endoplasmic reticulum (ER). The majority of these lipids reach the plasma membrane independently of the secretory vesicular pathway. Phospholipid delivery to the mitochondria and chloroplasts of plant cells also bypasses the secretory pathway and here it has been proposed that lysophospholipids are transported at contact sites between specific regions of the ER and the respective organelle, followed by lysophospholipid acylation in the target organelle. To test the hypothesis that a corresponding mechanism operates to transport phospholipids to the plasma membrane outside the secretory pathway, we investigated whether lysolipid acylation occurs also in the plant plasma membrane and whether this membrane, like the chloroplasts and mitochondria, is in close contact with the ER. RESULTS: The plant plasma membrane readily incorporated the acyl chain of acyl-CoA into phospholipids. Oleic acid was preferred over palmitic acid as substrate and acyl incorporation occurred predominantly into phosphatidylcholine (PC). Phospholipase A2 stimulated the reaction, as did exogenous lysoPC when administered in above critical micellar concentrations. AgNO3 was inhibitory. The lysophospholipid acylation reaction was higher in a membrane fraction that could be washed off the isolated plasma membranes after repeated freezing and thawing cycles in a medium with lowered pH. This fraction exhibited several ER-like characteristics. When plasma membranes isolated from transgenic Arabidopsis expressing green fluorescent protein in the ER lumen were observed by confocal microscopy, membranes of ER origin were associated with the isolated plasma membranes. CONCLUSION: We conclude that a lysoPC acylation activity is associated with plant plasma membranes and cannot exclude a PC transacylase activity. It is highly plausible that the enzyme(s) resides in a fraction of the ER, closely associated with the plasma membrane, or in both. We suggest that this fraction might be the equivalent of the mitochondria associated membrane of ER origin that delivers phospholipids to the mitochondria, and to the recently isolated ER-derived membrane fraction that is in close contact with chloroplasts. The in situ function of the lysoPC acylation/PC transacylase activity is unknown, but involvement in lipid delivery from the ER to the plasma membrane is suggested.

The involvement of cytosolic lipases in converting phosphatidyl choline to substrate for galactolipid synthesis in the chloroplast envelope.

Here we report that cytosolic phospholipases are involved in the utilization of phosphatidylcholine (PC) as substrate for chloroplast-localized synthesis of monogalactosyldiacylglycerol (MGDG). Isolated chloroplasts were pre-incubated with lysoPC and [14C]18:0-CoA to form [14C]PC. When soluble plant proteins (cytosol) and UDP-galactose were added, [14C] MGDG was formed. An inhibitor of phospholipase D markedly lowered the formation of [14C]MGDG, whereas thermolysin pretreatment of the chloroplasts was without effect. The cytosolic activity resided in the >100-kDa fraction. In a second approach, [14C]PC-containing lipid mixtures were incubated with cytosol. Degradation of [14C]PC to [14C]diacylglycerol was highest when the lipid composition of the mixture mimicked that of the outer chloroplast envelope. We also investigated whether PC of extraplastidic origin could function as substrate for MGDG synthesis. Isolated chloroplasts were incubated with enriched endoplasmic reticulum containing radiolabelled acyl lipids. In the presence of cytosol and UDP-galactose, there was a time-dependent transfer of [14C]PC from this fraction to chloroplasts, where [14C]MGDG was formed. We conclude that chloroplasts recruit cytosolic phospholipase D and phosphatidic acid phosphatase to convert PC to diacylglycerol. Apparently, these lipases do not interact with chloroplast surface proteins, but rather with outer membrane lipids, either for association to the envelope or for substrate presentation.

Acyl-CoA dependent acylation of phospholipids in the chloroplast envelope.

Acyl-CoAs are substrates for acyl lipid synthesis in the endoplasmic reticulum. In addition, they may also be substrates for lipid acylation in other membranes. In order to assess whether lipid acylation may have a role in plastid lipid metabolism, we have studied the incorporation of radiolabelled fatty acids from acyl-CoAs into lipids in isolated, intact pea chloroplasts. The labelled lipids were phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylinositol and free fatty acids. With oleoyl-CoA, the fatty acid was incorporated preferably into the sn-2 position of PC and the acylation activity mainly occurred in fractions enriched in inner chloroplast envelope. Added lysoPC stimulated the activity. With palmitoyl-CoA, the fatty acid was incorporated primarily into the sn-1 position of PG and the reaction occurred at the surface of the chloroplasts. As chloroplast-synthesized PG generally contains 16C fatty acids in the sn-2 position, we propose that the acylation of PG studied represents activities present in a domain of the endoplasmic reticulum or an endoplasmic reticulum-derived fraction that is associated with chloroplasts and maintains this association during isolation. This domain or fraction contains a discreet population of lipid metabolizing activities, different from that of bulk endoplasmic reticulum, as shown by that with isolated endoplasmic reticulum, acyl-CoAs strongly labelled phosphatidic acid and phosphatidylethanolamine, lipids that were never labelled in the isolated chloroplasts.

Detection and characterization of GTP-binding proteins in the chloroplast envelope of spinach (Spinacia oleracea).

Proteins binding guanosine triphosphate (GTP) have emerged as important regulators in several cellular processes in plants. To investigate any role of such proteins in chloroplast functions, we subjected envelope, stroma and thylakoid fractions isolated from spinach chloroplasts to two different GTP-binding assays. With both methods, we detected GTP-specific binding only in the envelope fraction. Two chloroplast envelope proteins with the apparent molecular weights of 30.5 and 33.5 kDa, respectively, bound [alpha-32P]GTP after SDS-PAGE followed by electroblotting onto a PVDF-membrane and renaturation. Both proteins were intrinsic proteins located in the outer chloroplast envelope. Also, when the fractions were incubated with [alpha-32P]GTP, followed by periodate oxidation and borohydride reduction to cross-link GTP to proteins, two proteins in the envelope fraction, of apparent molecular weights of 28 and 39 kDa, appeared to specifically bind GTP. When agents that stimulate heterotrimeric G-proteins, cholera toxin or the mastoparan analogue mas7, were added to isolated chloroplast envelope, the binding of radiolabelled GTP to the 39 kDa protein, a protein of the inner chloroplast envelope, was stimulated, whereas GTP-binding of the 28 kDa protein, a protein of the outer envelope, was unchanged. Mas7 also stimulated synthesis of monogalactosyl diacylglycerol in isolated chloroplast envelope. The occurrence and regulation of GTP-binding proteins in the chloroplast envelope suggests that GTP-binding proteins could be involved in communication with the extraplastidic compartment during chloroplast biogenesis and development.

Quality of life in patients with prostate cancer.

OBJECTIVES: Quality of life (QOL) issues are important for patients with prostate cancer because side effects from treatment are substantial, while the disease itself may be indolent. This article reviews prostate cancer QOL studies. DATA SOURCES: Selected studies published on QOL in prostate cancer using validated patient-assessed tools from the last 5 years. CONCLUSIONS: Prostate cancer treatments are associated with side effects: prostatectomy has more urinary and sexual side effects, while external radiation therapy has more bowel symptoms. Side effects are not highly correlated with overall QOL. IMPLICATIONS FOR NURSING PRACTICE: Patients must be made aware of potential gains in life expectancy as well as side effects of treatments to make informed decisions about treatment.

Electrocardiographic changes during total energy deprivation (fasting).

The effect of 10 days of total energy deprivation (fasting) on ECG reactions was evaluated in 14 healthy normal-weight males. The heart rate and the ratios between QRS and T wave amplitudes in leads I and II decreased significantly, as did body weight and blood glucose levels. The urinary excretion of adrenaline increased. It is concluded that other hormonal (e.g. thyroidal), neural and metabolic mechanisms are of greater significance for the heart than the sympatho-adreno-medullary activity during fasting. T wave abnormality without an abnormal Q wave and without other clinical symptoms was noted in one subject on the 8th day of starvation and remained abnormal for more than a year.