Activation of beta(2)-adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban, troponin I, and C-protein in ventricular myocardium from patients with terminal heart failure

Background-Catecholamines hasten cardiac relaxation through beta-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle. We assessed the role of beta(1)- and beta(2)-adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation. Methods and Results-Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n=5) or ischemic cardiomyopathy (n=5), were paced at 60 bpm. After measurement of the contractile and relaxant effects of epinephrine (10 mu mol/L) or zinterol (10 mu mol/L), mediated through beta(2)-adrenergic receptors, and of norepinephrine (10 mu mol/L), mediated through beta(1)-adrenergic receptors, tissues were freeze clamped. We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17, Data did not differ between the 2 disease groups and were therefore pooled. Epinephrine, zinterol, and norepinephrine increased contractile force to approximately the same extent, hastened the onset of relaxation by 15+/-3%, 5+/-2%, and 20+/-3%, respectively, and reduced the time to half-relaxation by 26+/-3%, 21+/-3%, and 37+/-3%. These effects of epinephrine, zinterol, and norepinephrine were associated with phosphorylation (pmol phosphate/mg protein) of phospholamban 14+/-3, 12+/-4, and 12+/-3, troponin I 40+/-7, 33+/-7, and 31+/-6; and C-protein 7.2+/-1.9, 9.3 +/- 1.4, and 7.5 +/- 2.0. Phosphorylation of phospholamban occurred at both Ser16 and Thr17 residues through both beta(1)- and beta(2)-adrenergic receptors. Conclusions-Norepinephrine and epinephrine hasten human ventricular relaxation and promote phosphorylation of implicated proteins through both beta(1)- and beta(2)-adrenergic receptors, thereby potentially improving diastolic function.

The dimerization and topological specificity functions of MinE reside in a structurally autonomous C-terminal domain

Correct placement of the division septum in Escherichia coli requires the co-ordinated action of three proteins, MinC, MinD and MinE. MinC and MinD interact to form a non-specific division inhibitor that blocks septation at all potential division sites. MinE is able to antagonize MinCD in a topologically sensitive manner, as it restricts MinCD activity to the unwanted division sites at the cell poles, Here, we show that the topological specificity function of MinE residues in a structurally autonomous, trypsin-resistant domain comprising residues 31-88, Nuclear magnetic resonance (NMR) and circular dichroic spectroscopy indicate that this domain includes both alpha and beta secondary structure, while analytical ultracentrifugation reveals that it also contains a region responsible for MinE homodimerization. While trypsin digestion indicates that the anti-MinCD domain of MinE (residues 1-22) does not form a tightly folded structural domain, NMR analysis of a peptide corresponding to MinE(1-22) indicates that this region forms a nascent helix in which the peptide rapidly interconverts between disordered (random coil) and alpha-helical conformations, This suggests that the N-terminal region of MinE may be poised to adopt an alpha-helical conformation when it interacts with the target of its anti-MinCD activity, presumably MinD.

The solution structure of the N-terminal zinc finger of GATA-1 reveals a specific binding face for the transcriptional co-factor FOG

Zinc fingers (ZnFs) are generally regarded as DNA-binding motifs. However, a number of recent reports have implicated particular ZnFs in the mediation of protein-protein interactions. The N-terminal ZnF of GATA-1 (NF) is one such finger, having been shown to interact with a number of other proteins, including the recently discovered transcriptional co-factor FOG. Here we solve the three-dimensional structure of the NF in solution using multidimensional H-1/N-15 NMR spectroscopy, and we use H-1/N-15 spin relation measurements to investigate its backbone dynamics. The structure consists of two distorted beta-hairpins and a single alpha-helix, and is similar to that of the C-terminal ZnF of chicken GATA-1. Comparisons of the NF structure with those of other C-4-type zinc binding motifs, including hormone receptor and LIM domains, also reveal substantial structural homology. Finally, we use the structure to map the spatial locations of NF residues shown by mutagenesis to be essential for FOG binding, and demonstrate that these residues all lie on a single face of the NE Notably, this face is well removed from the putative DNA-binding face of the NE an observation which is suggestive of simultaneous roles for the NF; that is, stabilisation of GATA-1 DNA complexes and recruitment of FOG to GATA-1-controlled promoter regions.

The tasks of medicine: An ideology of care; edited by Peter Baume

No abstract

Continuity of care and readmission in two service systems: a comparative Victorian and Groningen case-register study

Objective: We compared service consumption, continuity of care and risk of readmission in a record linkage follow-up study of cohorts of patients with schizophrenia and related disorders in Victoria (Australia) and in Groningen (The Netherlands). These areas are interesting to compare because mental health care is in a different stage of deiustitutionalization. More beds are available in Groningen and more community resources are available in Victoria. Method: The cohorts were followed for 4 years, since discharge from inpatient services using record linkage data available in the psychiatric case-registers in both areas. Survival analysis was used to study continuity of care and risk of readmission. Results: Available indicators showed a higher level of continuity of care in Victoria. While the relative risk of readmission was the same in both areas and not affected by aftercare contact after discharge, the number of days spent in hospital was much higher in the Groningen register area. Conclusion: These findings provide further support for earlier reports that the risk of readmission is predominantly affected by attributes of mental illness. However, the duration of admissions, is strongly affected by service system variables, including the provision of continuity of care.

A survey of contact with offspring and assistance with child care among parents with psychotic disorders

To help improve services for parents with psychotic disorders, patients with such disorders in three treatment agencies in Queensland, Australia, were surveyed about whether they were parents, how much contact they had with their offspring, and who provided assistance with child care. Of the 342 individuals with psychotic disorders mho participated in the study, 124 were parents. Forty-eight parents in the study had children under age 16, and 20 of these parents (42 percent) had their children living with them. Most parents relied on relatives or friends for assistance with child care. Barriers to child care services identified by parents were inability to pay, lack of local services, and fear of losing custody of children.

Suicide attempts by psychiatric patients in acute inpatient, long-stay inpatient and community care

Background: This study examined rates of and risk factors associated with suicide attempts by psychiatric patients under active care. It was especially focussed on the relative rates across three standard treatment settings: acute inpatient care, long-stay inpatient care and community-based carl. Methods: A total of 12,229 patients in 13,632 episodes of care were rated on the Health of the Nation Outcome Scales (HoNOS) Item 2. For the purposes of the current investigation, a score of 4 was deemed to indicate a suicide attempt. Results: Incidence densities per 1000 episode days were 5.4 (95% CI = 4.8-6.1) for patients under care in acute inpatient settings, 0.6 (95% CI = 0.5-0.8) for patients under care in long-stay inpatient settings, and 0.5 (95% CI = 0.5-0.6) for patients under carl in community-based arrangements. Predictors varied by treatment setting. Risk was elevated for personality disorders across all settings: 22.7 attempts per 1000 episode days (95% CI = 17.2-30.0) in acute inpatient care; 2.1 (95% CI = 1.0-4.5) in long-stay inpatient care; and 2.3 (95% CI = 1.7-3.0) in community-based care. This effect remained after adjustment for demographics. Conclusion: Rates of suicide attempts among psychiatric patients are a major issue facing contemporary mental health care systems, and risk factors vary across different treatment settings.

Community care and criminal offending in schizophrenia

Background The introduction of community care in psychiatry is widely thought to have resulted in more offending among the seriously mentally ill. This view affects public policy towards and public perceptions of such people. We investigated the association between the introduction of community care and the pattern of offending in patients with schizophrenia in Victoria, Australia. Methods We established patterns of offending from criminal records in two groups of patients with schizophrenia over their lifetime to date and in the 10 years after their first hospital admission. One group was first admitted in 1975 before major deinstitutionalisation in Victoria, the second group in 1985 when community care was becoming the norm. Each patient was matched to a control, by age, sex, and place of residence to allow for changing patterns of offending over time in the wider community. Findings Compared with controls, significantly more of those with schizophrenia were convicted at least once for ail categories of criminal offending except sexual offences (relative risk of offending in 1975=3.5 [95% CI 2.0-5.5), p=0.001, in 1985=3.0 [1.9-4.9], p=0.001). Among men, more offences were committed in the 1985 group than the 1975 group, but this was matched by a similar increase in convictions among the community controls. Those with schizophrenia who had also received treatment for substance abuse accounted for a disproportionate amount of offending. Analysis of admission data for the patients and the total population of admissions with schizophrenia showed that although there had been an increase of 74 days per annum spent in the community for each of the study population as a whole, first admissions spent only 1 more day in the community in 1985 compared with 1975. Interpretation Increased rates in criminal conviction for those with schizophrenia over the last 20 years are consistent with change in the pattern of offending in the general community. Deinstitutionalisation does not adequately explain such change. Mental-health services should aim to reduce the raised rates of criminal offending associated with schizophrenia, but turning the clock back on community care is unlikely to contribute towards any positive outcome.

Functional assessment and care of children with neurodevelopmental disabilities

Objectives: To determine the relationship between pediatric assessment scores and ratings by parents and teachers regarding the amount of assistance required to complete basic activities of daily living; and to examine the relationship among scores for three commonly used pediatric assessments. Design: Prospective correlational study. 205 children with developmental disabilities. The children ranged in age from 11 to 87 mo and included 72 females and 133 males of diverse socioeconomic and ethnic backgrounds. The children were evaluated by using the Battelle Developmental Inventory Screening Test, Vineland Adaptive Behavior Scales, Functional Independence Measure for Children (WeeFIM(TM) instrument), and the Amount of Assistance Questionnaire, Results: The test-retest reliability coefficients for items on the Amount of Assistance Questionnaire were found to range from 0.82 to 0.97. Correlations among subscale scores and amount of assistance ratings were highest for the WeeFIM instrument and Battelle Developmental Inventory Screening Test. The highest correlation was between WeeFIM total rating and total amount of assistance rating (r = 0.91). Conclusion: Total WeeFIM instrument ratings and severity of disability were the best predictors of amount of assistance ratings provided by parents and teachers.

The clinical value compass: Achieving benchmarking and quality improvement in aged care

Quality measurement and benchmarking in aged cave presents several challenges. A model which addresses this by linking four dimensions of outcomes has been developed - the Clinical Value Compass (CVC). A CVC was developed for stroke rehabilitation and measured across four sites. The CVC teas well accepted by the treatment teams and proved practical to measure. The results revealed differences in practices and client groups that led to a closer analysis of process and subsequent changes in these processes. Remeasuring of the CVC is required to demonstrate improved outcomes arising from these process changes.

Perceived need for mental health care, findings from the Australian National Survey of Mental Health and Well-being

Background. The Australian National Survey of Mental Health and Well-being was designed to detect and describe psychiatric morbidity, associated disability, service use and perceived need for care. The survey employed a single-phase interview methodology, delivering a field questionnaire to a clustered probability sample of 10641 Australians. Perceived need was sampled with an instrument designed for this survey, the Perceived Need for Care Questionnaire (PNCQ). This questionnaire gathers information about five categories of perceived need, assigning each to one of four levels of perceived need. Reliability and validity studies showed satisfactory performance of the instrument. Methods. Perceived need for mental health care in the Australian population has been analysed using PNCQ data, relating this to diagnostic and service utilization data from the above survey. Results. The survey findings indicate that an estimated 13.8 % of the Australian population have perceived need for mental health care. Those who met interview criteria for a psychiatric diagnosis and also expressed perceived need make up 9.9 % of the population. An estimated 11.0% of the population are cases of untreated prevalence, a minority (3.6% of the population) of whom expressed perceived need for mental health care. Among persons using services, those without a psychiatric diagnosis based on interview criteria (4.4% of the population), showed high levels of perceived met need. Conclusions. The overall rate of perceived need found by this methodology lies between those found in the USA and Canada. The findings suggest that service use in the absence of diagnosis elicited by survey questionnaires may often represent successful intervention. In the survey, untreated prevalence was commonly not accompanied by perceived need for mental health care.

The development and evaluation of an incontinence screening questionnaire for female primary care

Although there is a high prevalence of leaking urine among Australian women, there are currently no standardized procedures for screening patients for incontinence in the primary care setting (known in Australia as general practice). In response to this, an incontinence screening questionnaire (ISQ) was developed and evaluated for use in general practice. Eighty-nine women completed an original compilation of 33 items that asked about situations associated with leaking urine, avoidance of leakage, and concern about leakage. Each item was assessed according to its acceptability for the population of female general practice patients, discriminative value, and test-retest reliability. These patients also underwent an objective test of incontinence, the 48-hour pad test, so that the screening items could be validated against an objective classification of incontinence. The study included women who had bladder control problems and those who did not. Eight items on the ISQ were shown to be acceptable to patients, discriminative, reliable, and valid indicators of objective incontinence. Five items were capable of predicting almost 70% of patients who showed objective leakage of urine and misclassified fewer than 15% of these patients. Those five items were selected for inclusion in the (refined) ISQ. (C) 2000 Wiley-Liss, Inc.