Differential distribution of estrogen receptor (ER)-alpha and ER-beta in the midbrain raphe nuclei and periaqueductal gray in male mouse: Predominant role of ER-beta in midbrain serotonergic systems

We examined the distribution of estrogen receptor (ER)-alpha and ER-beta immunoreactive (ir) cells in the dorsal (DRN) and median/paramedian (MPRN) raphe nuclei in male mice. ER-alpha ir neurons were scattered across the three subdivisions (ventral, dorsal, and lateral) of the DRN and the MPRN. Robust ER-beta ir cells were observed throughout the raphe nuclei, and were particularly abundant in the ventral and dorsal subdivisions of the DRN. Using dual-label immunocytochemistry for ER-alpha or ER-beta with tryptophan hydroxylase (TPH), the rate-limiting enzyme for 5-hydroxytryptamine (5-HT) synthesis, over 90% of ER-beta ir cells exhibited TPH-ir in all DRN subdivisions, whereas only 23% of ER-alpha ir cells contained TPH. Comparisons of ER-alpha knockout (alphaERKO) as well as ER-beta knockout (betaERKO) mice with their respective wild-type (WT) littermates revealed that gene disruption of either ER-alpha or ER-beta did not affect the other ER subtype expression in the raphe nuclei. In situ hybridization histochemistry revealed that there was a small but statistically significant decrease in TPH mRNA expression in the ventral DRN subdivision in betaERKO mice compared with betaWT mice, whereas TPH mRNA levels were not affected in alphaERKO mice. These findings support a hypothesis that ER-beta activation may contribute to the estrogenic regulation of neuroendocrine and behavioral functions, in part, by acting directly on 5-HT neurons in the raphe nuclei in male mice.     

Role of NK cells and gamma interferon in transplacental passage of Toxoplasma gondii in a mouse model of primary infection

Protective immunity in mice infected with Toxoplasma gondii is mainly mediated by NK cells, CD4 and CD8 T cells, and type 1 cytokines, such as gamma interferon (IFN-gamma). To clarify the roles of NK cells and IFN-gamma in protection against primary congenital toxoplasmosis, we used recombination activating gene 2 knockout (RAG-2(-/-)) mice, which lack T and B lymphocytes, in comparison with the wild-type BALB/c model. RAG-2(-/-) mice had a significantly lower risk of fetal toxoplasmosis than BALB/c mice (25 versus 63.9%; P = 0.003). This protection was associated with an increased number of maternal NK cells, IFN-gamma secretion by spleen cells, and decreased parasitemia. In the RAG-2(-/-) mice, NK cell depletion increased both the rate of fetal infection, to 56.5% (P = 0.02), and the blood parasite burden. Conversely, in the BALB/c mice, this treatment did not modify maternofetal transmission or the blood parasite burden. Neutralization of IFN-gamma in both infected RAG-2(-/-) and BALB/c mice decreased congenital Toxoplasma transmission, contrasting with an exacerbation of maternal infection. These data suggest that a partially protective immunity against congenital toxoplasmosis is achieved due to the increased number of NK cells in RAG-2(-/-) mice. However, it seems that IFN-gamma enhances, directly or indirectly, the transplacental transmission.     

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Recruiting and retaining GPs and patients in intervention studies: the DEPS-GP project as a case study

Background  

Recruiting and retaining GPs for research can prove difficult, and may result in sub-optimal patient participation where GPs are required to recruit patients. Low participation rates may affect the validity of research.     

Patients feeling severely affected by multiple sclerosis: How do patients want to communicate about end-of-life issues?

Objective

Investigate multiple sclerosis patients’ desire to communicate with their physicians about their disease progression and end-of-life issues.

Methods

Persons meeting the inclusion criteria of feeling severely affected by MS were invited via the German MS society to complete a needs questionnaire. Replies to questions on physician empathy and wishes about communication regarding disease progression and death and dying were quantitatively analyzed. Endpoints (point 1 + 2/4 + 5) of 5-point-likert scales are summarized under results.

Results

573 of 867 questionnaires meeting our criteria were analyzed. In response to a general question 64% (n = 358) indicated a wish for disease progression and death and dying to be addressed by their doctor. A majority (76%, n = 427) considered it important that progression of their disease be discussed, while 44% (n = 246) regard addressing death and dying as unimportant. No objective disease criteria could be identified to explain the wish for communicating end-of-life issues. Doctors who were retrospectively viewed as avoiding raising critical aspects of the illness were perceived as less empathetic (p < 0.001).

Conclusion

People with MS have a desire to talk about progression of their disease with their doctors.

Practice implications

Physicians should be empathetic in raising critical aspects of the patients’ illness individually.     

Trust, social support and patient type--associations between patients perceived trust, supportive communication and patients preferences in regard to paternalism, clarification and participation of severely injured patients

Objective

Trust is an important aspect of physician–patient-interaction, both in terms of compliance and patient- and physician-reported outcomes. Trust-building communication is especially important in terms of severely injured patients because of severity of their injuries and frequently associated physical and psychological consequences. Patients preferences concerning medical treatment (patient type) is also regarded to be important in terms of trust. The objective of this study was to investigate the relationships between patients perceived trust, supportive communication of physicians and patient type of severely injured patients.

Methods

Seventy-one severely injured patients, who were predominantly injured in the workplace or in traffic accidents and were treated in one of four hospitals in Northrhine-Westfalia between 2001 and 2005, completed a self-administered questionnaire. “Trust in physicians_short form” (TRIP_sf) describes different aspects, such as general trust, competence of doctors and the feeling to be in good hands. “Informational support” and “emotional support” comprise verbal and non-verbal aspects, such as clear and understandable information or devotion and empathic manner. “Patient type” measures patients preferences in regard to paternalism of physician, clarification of medical facts and participation in treatment.

Results

Trust is strongly correlated with informational (.628**) and emotional support (.542**) and is less correlated with patients preferences of “paternalism” (.250*)“, “clarification” (.438**) and participation” (.378**). Informational and emotional support are in general not significantly correlated with type of patient, all correlations were adjusted for age, gender, marital and socioeconomic status, length of hospital stay, and severity of injury.

Conclusions

Trust is significantly related to patient type but more related to doctor support: the results confirm the importance of supportive communication in terms of emotional and informational support.

Practice implications

Medical education should integrate sound knowledge about the psychosocial aspects of physician patient interaction to enable doctors to provide effective social support and to identify and consider patients preferences.     

Hormonal and genetic influences on behavioral dispositions related to reproduction

Summary Success in elucidating neural and genetic mechanisms for a female-typical sociosexual behavior have encouraged new work on mechanisms for the underlying concepts, motivation and arousal. Evidence for global arousal is adduced, and brainstem pathways contributing to global arousal are under investigation. Accepted June 26, 2002; Published online September 16, 2002 Correspondence: Donald Pfaff, M.D., Laboratory of Neurobiology and Behavior, Box 275, The Rockefeller University, 1230 York Avenue, New York, NY 10021, U.S.A. E-mail: pfaff@rockvax.rockefeller.edu     

Physician empathy and subjective evaluation of medical treatment outcome in trauma surgery patients

Objective

To analyze whether patients’ perception of their medical treatment outcome is higher among patients who experienced a higher empathy by trauma surgeons during their stay in hospital.

Methods

127 patients were surveyed six weeks after discharge from the trauma surgical general ward. Subjective evaluation of medical treatment outcome was measured with the corresponding scale from the Cologne Patient Questionnaire. Clinical empathy was assessed by using the CARE measure. The influence of physician empathy and control variables on a dichotomized index of subjective evaluation of medical treatment outcome was identified with a logistic regression.

Results

120 patients were included in the logistic regression analysis. Compared to patients with physician empathy ratings of less than 30 points, patients with ratings of 41 points or higher have a 20-fold higher probability to be in the group with a better medical treatment outcome on the CPQ-scale (α-level < .001, R² 46.9).

Conclusion

Findings emphasize the importance of a well-functioning relationship between physician and patient even in a surgical setting where the focus is mostly on the bare medical treatment.

Practice implications

Communication trainings i.e. in surgical education can be an effective way to improve the ability to show empathy with patients’ concerns.