Indirect induction of radiation lymphomas in mice. Evidence for a novel, transmissible leukemogen.

The transmission of a lymphomagenic agent(s) from the bone marrow of irradiated mice to thymic target cells has been demonstrated by: (a) the induction of T cell lymphomas in nonirradiated thymic grafts implanted in irradiated, Thy-l-congenic mice, (b) the induction of T cell lymphomas of host origin in mice infused with bone marrow from irradiated, Thy-l-congenic donors. The latter procedure also yields an appreciable number of pre-B cell lymphomas of uncertain origin. The results confirm Kaplan's theory that radiation induces thymic lymphomas in mice by an indirect mechanism. However, the previously described radiation leukemia virus is clearly not involved in the majority of transferred lymphomas. We propose that the mediating agent in radiation lymphomagenesis is a novel, transmissible agent induced in the bone marrow, but exerting its transforming activity on cells in the thymus. The nature and mode of action of the agent are under investigation

The Genetics Journey: A Case Report of a Genetic Diagnosis Made 30 Years Later

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare autosomal dominant condition that was first described in 2006. The causative gene, EFTUD2, identified in 2012. We report on a family that initially presented to a pediatric genetics clinic in the 1980s for evaluation of multiple congenital anomalies. Re‐evaluation of one member thirty years later resulted in a phenotypic and molecularly confirmed diagnosis of MFDM. This family’s clinical histories and the novel EFTUD2 variant identified, c.1297_1298delAT (p.Met433Valfs*17), add to the literature about MFDM. This case presented several genetic counseling challenges and highlights that “the patient” can be multiple family members. We discuss testing considerations for an unknown disorder complicated by the time constraint of the patient’s daughter’s pregnancy and how the diagnosis changed previously provided recurrence risks. Of note, 1) the 1980s clinic visit letters provided critical information about affected family members and 2) the patient’s husband’s internet search of his wife’s clinical features also yielded the MFDM diagnosis, illustrating the power of the internet in the hands of patients. Ultimately, this case emphasizes the importance of re‐evaluation given advances in genetics and the value of a genetic diagnosis for both patient care and risk determination for family members.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147210/1/jgc40894.pd

Feasibility, safety and tolerability of accelerated dobutamine stress echocardiography

A continuous infusion of a single high dose of dobutamine has been, recently, suggested as a simple and effective protocol of stress echocardiography. The present study assesses the feasibility, safety, and tolerability of an accelerated dobutamine stress protocol performed in patients with suspected or known coronary artery disease. Two hundred sixty five consecutive patients underwent accelerated dobutamine stress echocardiography: the dobutamine was administered at a constant dose of 50 μg/kg/min for up to 10 minutes. The mean weight-adjusted cumulative dose of dobutamine used was 330 ± 105.24 μg/kg. Total duration of dobutamine infusion was 6.6 ± 2.1 min. Heart rate rose from 69.9 ± 12.1 to 123.1 ± 22.1 beats/min at peak with a concomitant change in systolic blood pressure (127.6 ± 18.1 vs. 167.6 ± 45.0 mmHg). Dobutamine administration produced a rapid increase in heart rate (9.4 ± 5.9 beats/min2). The side effects were similar to those described with the standard protocol; the most common were frequent premature ventricular complexes (21.5%), frequent premature atrial complexes (1.5%) and non sustained ventricular tachycardia (1.5%); among non cardiac symptoms the most frequent were nausea (3.4%), headache (1.1%) and symptomatic hypotension (1.1%). No major side effects were observed during the test. Our data demonstrate that a continous infusion of a single high dose of dobutamine is a safe and well tolerated method of performing stress echocardiography in patients with suspected or known coronary artery disease. This new protocol requires the administration of lower cumulative dobutamine dose than standard protocol and results in a significant reduction in test time

Preventive interventions in families with parental depression: children’s psychosocial symptoms and prosocial behaviour

The aim is to document the effectiveness of a preventive family intervention (Family Talk Intervention, FTI) and a brief psychoeducational discussion with parents (Let’s Talk about the Children, LT) on children’s psychosocial symptoms and prosocial behaviour in families with parental mood disorder, when the interventions are practiced in psychiatric services for adults in the finnish national health service. Patients with mood disorder were invited to participate with their families. Consenting families were randomized to the two intervention groups. The initial sample comprised 119 families and their children aged 8–16. Of these, 109 completed the interventions and the baseline evaluation. Mothers and fathers filled out questionnaires including standardized rating scales for children’s symptoms and prosocial behaviour at baseline and at 4, 10 and 18 months post-intervention. The final sample consisted of parental reports on 149 children with 83 complete data sets. Both interventions were effective in decreasing children’s emotional symptoms, anxiety, and marginally hyperactivity and in improving children’s prosocial behaviour. The FTI was more effective than the LT on emotional symptoms particularly immediately after the intervention, while the effect of the LT emerged after a longer interval. The study supports the effectiveness of both interventions in families with depressed parents. The FTI is applicable in cultural settings other than the USA. Our findings provide support for including preventive child mental health measures as part of psychiatric services for mentally ill parents

Cognitive reactivity: cultural adaptation and psychometric testing of the Persian version of the Leiden Index of Depression Sensitivity Revised (LEIDS-R) in an Iranian sample

Cognitive reactivity (CR) to the experimental induction of sad mood has been found to predict relapse in recovered depressed patients. The Leiden Index of Depression Sensitivity Revised (LEIDS-R) is a self-report measure of CR. The aim of the present study was to establish the validity and reliability of the Persian version of the LEIDS-R. The participants were recovered depressed and non-depressed Iranian individuals (n = 833). The analyses included content validation, factor analysis, construct validity, and reliability testing. Preliminary construct validation analysis confirmed that factor analysis was appropriate for the Persian version of the LEIDS-R. Factor analysis displayed similar factor loadings to the original English version. The total internal consistency of the translated version, which was assessed using Cronbach’s alpha coefficient, was equal to 0.90. The test-retest reliability of the total score was equal to that of the test-retest conducted after a two-week interval at 0.94. Content validity, face validity, and construct validity, as well as reliability analysis were all found to be satisfactory for the Persian version of the LEIDS-R. The Persian version of the LEIDS-R appears to be valid and reliable for use in future studies, and has properties comparable to the original version and to that obtained in previous studies

Opposing effects of D-aspartic acid and nitric oxide on tuning of testosterone production in mallard testis during the reproductive cycle

<p>Abstract</p> <p>Background</p> <p>D-Aspartic acid (D-Asp) and nitric oxide (NO) play an important role in tuning testosterone production in the gonads of male vertebrates. In particular, D-Asp promotes either the synthesis or the release of testosterone, whereas NO inhibits it. In this study, we have investigated for the first time in birds the putative effects of D-Asp and NO on testicular testosterone production in relation to two phases of the reproductive cycle of the adult captive wild-strain mallard (Anas platyrhynchos) drake. It is a typical seasonal breeder and its cycle consists of a short reproductive period (RP) in the spring (April-May) and a non reproductive period (NRP) in the summer (July), a time when the gonads are quiescent. The presence and the localization of D-Asp and NO in the testis and the trends of D-Asp, NO and testosterone levels were assessed during the main phases of the bird's reproductive cycle. Furthermore, in vitro experiments revealed the direct effect of exogenously administered D-Asp and NO on testosterone steroidogenesis.</p> <p>Methods</p> <p>By using immunohistochemical (IHC) techniques, we studied the presence and the distributional pattern of D-Asp and NO in the testes of RP and NRP drakes. D-Asp levels were evaluated by an enzymatic method, whereas NO content, via nitrite, was assessed using biochemical measurements. Finally, immunoenzymatic techniques determined testicular testosterone levels.</p> <p>Results</p> <p>IHC analyses revealed the presence of D-Asp and NO in Leydig cells. The distributional pattern of both molecules was in some way correlated to the steroidogenic pathway, which is involved in autocrine testosterone production. Indeed, whereas NO was present only during the NRP, D-Asp was almost exclusively present during the RP. Consistently, the high testosterone testicular content occurring during RP was coupled to a high D-Asp level and a low NO content in the gonad. By contrast, in sexually inactive drakes (NRP), the low testosterone content in the gonad was coupled to a low D-Asp content and to a relatively high NO level. Consequently, to determine the exogenous effects of the two amino acids on testosterone synthesis, we carried out in vitro experiments using testis sections deriving from both the RP and NRP. When testis slices were incubated for 60 or 120 min with D-Asp, testosterone was enhanced, whereas in the presence of L-Arg, a precursor of NO, it was inhibited.</p> <p>Conclusion</p> <p>Our results provide new insights into the involvement of D-Asp and NO in testicular testosterone production in the adult captive wild-strain mallard drake. The localization of these two molecules in the Leydig cells in different periods of the reproductive cycle demonstrates that they play a potential role in regulating local testosterone production.</p

Interpersonal psychotherapy (IPT) for late-life depression in general practice: uptake and satisfaction by patients, therapists and physicians

<p>Abstract</p> <p>Background</p> <p>Interpersonal Psychotherapy (IPT) is recommended in most depression treatment guidelines and proved to be a suitable treatment for elderly depressed patients. Despite the favorable results of IPT in research populations, the dissemination to general practice is surprisingly limited. Little is known about uptake and satisfaction when this therapy is introduced into real-life general practice.</p> <p>Methods</p> <p>Motivation and evaluation of patients, GPs and therapists were recorded and organizational barriers described alongside a randomized controlled trial. IPT, given by mental health workers, was compared with usual general practitioner (GP) care. Included were patients (≥55 years) who met the DSM-IV criteria for major depressive disorder.</p> <p>Results</p> <p>Patients were motivated for the psychotherapy intervention: of the 205 eligible patients, 143 (70%) entered the study, and of the 69 patients who were offered IPT, 77% complied with the treatment. IPT proved to be an attractive therapy for patients as well as for therapists from mental health organizations. General practitioners evaluated the intervention positively afterwards, mainly because of the time-limited and structured approach. Organizational barriers: no IPT therapists were available; an IPT trainer and supervisor had to be trained and training materials had to be developed and translated. Additionally, there was a lack of office space in some general practices; for therapists from private practices it was not feasible to participate because of financial reasons. IPT was superior to usual care in patients with moderate to severe depression.</p> <p>Conclusion</p> <p>As we succeeded in delivering IPT in primary care practice, and as IPT was superior to usual care, there are grounds to support the implementation of IPT for depressed elderly patients within general practice, as long as the practices have room for the therapists and financial barriers can be overcome. Consolidation may be achieved by making this intervention available through practice nurses or community psychiatric nurses who deliver IPT as part of a more comprehensive depression management program.</p

The devil is in the details: trends in avoidable hospitalization rates by geography in British Columbia, 1990–2000

BACKGROUND: Researchers and policy makers have focussed on the development of indicators to help monitor the success of regionalization, primary care reform and other health sector restructuring initiatives. Certain indicators are useful in examining issues of equity in service provision, especially among older populations, regardless of where they live. AHRs are used as an indicator of primary care system efficiency and thus reveal information about access to general practitioners. The purpose of this paper is to examine trends in avoidable hospitalization rates (AHRs) during a period of time characterized by several waves of health sector restructuring and regionalization in British Columbia. AHRs are examined in relation to non-avoidable and total hospitalization rates as well as by urban and rural geography across the province. METHODS: Analyses draw on linked administrative health data from the province of British Columbia for 1990 through 2000 for the population aged 50 and over. Joinpoint regression analyses and t-tests are used to detect and describe trends in the data. RESULTS: Generally speaking, non-avoidable hospitalizations constitute the vast majority of hospitalizations in a given year (i.e. around 95%) with AHRs constituting the remaining 5% of hospitalizations. Comparing rural areas and urban areas reveals that standardized rates of avoidable, non-avoidable and total hospitalizations are consistently higher in rural areas. Joinpoint regression results show significantly decreasing trends overall; lines are parallel in the case of avoidable hospitalizations, and lines are diverging for non-avoidable and total hospitalizations, with the gap between rural and urban areas being wider at the end of the time interval than at the beginning. CONCLUSION: These data suggest that access to effective primary care in rural communities remains problematic in BC given that rural areas did not make any gains in AHRs relative to urban areas under recent health sector restructuring initiatives. It remains important to continue to monitor the discrepancy between them as a reflection of inequity in service provision. In addition, it is important to consider alternative explanations for the observed trends paying particular attention to the needs of rural and urban populations and the factors influencing local service provision