Inhibition of an anti-Pr1d cold agglutinin by citrate present in commercial red cell preservative solutions

A patient with known cold autoimmune hemolyticanemia was admitted for surgery. Routine cold agglutinin evaluations, using commercial red cells (RBCs) in modified Alsever's preservative solution, revealed a cold agglutinin titer of 4 to 16. However, using RBCs washed four times with saline, a high-titer (greater than 2000 at 4 degrees C) cold autoagglutinin was demonstrated. The cold agglutinin was shown to be an IgM kappa paraprotein with anti-Pr1d specificity. The addition of Alsever's solution to washed RBCs inhibited the cold agglutinin. Each major component of Alsever's solution (neomycin, chloramphenicol, inosine, dextrose, and citrate) was tested individually; only citrate inhibited the patient's cold agglutinin. Various compounds structurally related to citrate were tested and found to cause various degrees of inhibition. The strongest inhibition correlated with the presence of either three carboxyl groups on molecules devoid of double-bonded carbon atoms or two carboxyl groups in cis configuration. A panel of 54 cold agglutinins, including 7 with anti-Pr specificity, was analyzed. None was significantly inhibited by Alsever's solution, although one with anti-Pr2 specificity was weakly inhibited. In summary, these studies describe an anti-Pr1d cold autoagglutinin that was inhibited by citrate in RBC preservative solutions. The failure to detect such a cold agglutinin can result from not washing RBCs free of citrate before testing.     

Family physician views about primary care reform in Ontario: a postal questionnaire

Background  

Primary care reform initiatives in Ontario are proceeding with little information about the views of practicing family physicians.     

Patient-reported outcomes in the Translational Breast Cancer Research Consortium

Members of the Translational Breast Cancer Research Consortium conducted an expert-driven literature review to identify a list of domains and to evaluate potential measures of these domains for inclusion in a list of preferred measures. Measures were included if they were easily available, free of charge, and had acceptable psychometrics based on published peer-reviewed analyses. A total of 22 domains and 52 measures were identified during the selection process. Taken together, these measures form a reliable and validated list of measurement tools that are easily available and used in multiple cancer trials to assess patient-reported outcomes in relevant patients.     

Pharmacological preconditioning by diazoxide downregulates cardiac L-type Ca2+ channels

BACKGROUND AND PURPOSE

Pharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K⁺ (mitoK_ATP) channel openers such as diazoxide, leads to cardioprotection against ischaemia. However, effects on Ca²⁺ homeostasis during PPC, particularly changes in Ca²⁺ channel activity, are poorly understood. We investigated the effects of PPC on cardiac L-type Ca²⁺ channels.

EXPERIMENTAL APPROACH

PPC was induced in isolated hearts and enzymatically dissociated cardiomyocytes from adult rats by preincubation with diazoxide. We measured reactive oxygen species (ROS) production and Ca²⁺ signals associated with action potentials using fluorescent probes, and L-type currents using a whole-cell patch-clamp technique. Levels of the α_1c subunit of L-type channels in the cellular membrane were measured by Western blot.

KEY RESULTS

PPC was accompanied by a 50% reduction in α_1c subunit levels, and by a reversible fall in L-type current amplitude and Ca²⁺ transients. These effects were prevented by the ROS scavenger N-acetyl-L-cysteine (NAC), or by the mitoK_ATP channel blocker 5-hydroxydecanoate (5-HD). PPC signficantly reduced infarct size, an effect blocked by NAC and 5-HD. Nifedipine also conferred protection against infarction when applied during the reperfusion period. Downregulation of the α_1c subunit and Ca²⁺ channel function were prevented in part by the protease inhibitor leupeptin.

CONCLUSIONS AND IMPLICATIONS

PPC downregulated the α_1c subunit, possibly through ROS. Downregulation involved increased degradation of the Ca²⁺ channel, which in turn reduced Ca²⁺ influx, which may attenuate Ca²⁺ overload during reperfusion.     

Life Satisfaction and Subsequent Physical,Behavioral, and Psychosocial Health in Older Adults

Policy Points

• Several intergovernmental organizations (Organisation for Economic Co‐operation and Development, World Health Organization, United Nations) are urging countries to use well‐being indicators (e.g., life satisfaction) in addition to traditional economic indicators when making important policy decisions.
• As the number of governments implementing this new approach grows, so does the need to continue evaluating the health and well‐being outcomes we might observe from policies aimed at improving life satisfaction.
• The results of this study suggest that life satisfaction is a valuable target for policies aiming to enhance several indicators of psychosocial well‐being, health behaviors, and physical health outcomes.

ContextSeveral intergovernmental organizations (Organisation for Economic Co‐operation and Development, World Health Organization, United Nations) are urging countries to use well‐being indicators (e.g., life satisfaction) in addition to traditional economic indicators when making important policy decisions. As the number of governments implementing this new approach grows, so does the need to continue evaluating the health and well‐being outcomes we might observe from policies aimed at improving life satisfaction.MethodsWe evaluated whether positive change in life satisfaction (between t₀;2006/2008 and t₁;2010/2012) was associated with better outcomes on 35 indicators of physical, behavioral, and psychosocial health and well‐being (in t₂;2014/2016). Data were from 12,998 participants in the University of Michigan''s Health and Retirement Study—a prospective and nationally representative cohort of US adults over age 50.FindingsParticipants with the highest (versus lowest) life satisfaction had better subsequent outcomes on some physical health indicators (lower risk of pain, physical functioning limitations, and mortality; lower number of chronic conditions; and higher self‐rated health) and health behaviors (lower risk of sleep problems and more frequent physical activity), and nearly all psychosocial indicators (higher positive affect, optimism, purpose in life, mastery, health mastery, financial mastery, and likelihood of living with spouse/partner; and lower depression, depressive symptoms, hopelessness, negative affect, perceived constraints, and loneliness) over the 4‐year follow‐up period. However, life satisfaction was not subsequently associated with many specific health conditions (i.e., diabetes, hypertension, stroke, cancer, heart disease, lung disease, arthritis, overweight/obesity, or cognitive impairment), other health behaviors (i.e., binge drinking or smoking), or frequency of contact with children, family, or friends.ConclusionsThese results suggest that life satisfaction is a valuable target for policies aiming to enhance several indicators of psychosocial well‐being, health behaviors, and physical health outcomes.     

A SURVEY OF NEUROLOGICAL DISABILITY AT A DISTRICT GENERAL HOSPITAL

SUMMARY Neurological disease accounts for 20% of all admissions to medical wards, but the number of inpatients with neurological disability is unknown. The notes of all adult inpatients in a district general hospital were reviewed to identify all those with a neurological disorder. Over 40% of inpatients on medical wards and 4% on surgical wards had a neurological disorder. Stroke was the most common neurological diagnosis, accounting for 36% of neurological disorders and 22% of all patients on medical wards. Other neurological diagnoses included dementias 10%, degenerative disorders 10%, epilepsy 7%, demyelination 4%, and head injuries 3%. Neurological patients have long inpatient stays (mean 80 days), and often remain in hospital awaiting changes in accommodation. Seven patients under 65 years stayed more than 6 months awaiting long-term care. Neurological disorders contribute significantly to the inpatient workload. Identifying those requiring rehabilitation and concentrating them on one ward could improve the quality and efficiency of their care.     

A Pilot for Understanding Interdisciplinary Teams in Rehabilitation Practice

Interdisciplinary teams in rehabilitation are effective for positive patient outcomes. They require skills in team building and interprofessional collaboration. The Institute of Medicine has interdisciplinary teams as one of the five core competencies for healthcare workers. In reviewing the literature on teams, several themes were developed, such as communication, collaboration, understanding of roles, and educational levels of team members. Using these themes, a survey was developed to assess perceptions of teams by rehabilitation nurses, physical therapists, and occupational therapists. Significant findings came from questions on educational levels of team members between nurses and occupational therapists and also within the nursing groups. Open‐ended questions asked about barriers and facilitators for effective teams. We hope that these pilot results will lead to discussions on how to improve interdisciplinary teams and make them more effective for better patient outcomes.     

Subtypes of B44 in six different populations.

We have investigated the distribution of HLA-B44 subtypes in various populations, see table. Of the five B44 subtypes investigated, two are apparently quite rare because they were only found in the local central european panel (B^*4404 and B^*4406). The european populations are characterized by a relatively high frequency of B^*4402, while in the Albanian, in the Asiatic and African populations, the subtype B^*4403 is prevailing. The distribution of the B44 subtypes in the Czech and the Munich population are virtually the same. We conclude from these data, that B44 subtypes have different distributions in different populations of the world and must therefore be taken into consideration when matching for bone marrow transplantation.