Chronic morphine and testosterone treatment. Effects on sexual behavior and dopamine metabolism in male rats

The effects of sustained delivery of morphine and/or testosterone (T) on male rat copulatory behavior, penile reflexes and dopaminergic metabolism in selected brain regions were examined. Castration was followed by (1) a decrease in the number of male rats exhibiting intromissive and ejaculatory behavior in mating tests, (2) decreased erections in ex copula tests, and (3) increases in dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations in the mediobasal hypothalamus (MBH) and the preoptic area-anterior hypothalamus (POA-AH). The decreased incidence of copulatory behavior and penile reflexes seen after castration was effectively prevented by a 4-day treatment with 5-mm T-containing Silastic capsules. Chronic morphine implants, conversely, accentuated the castration-induced decrements in copulatory behavior and prevented the 5-mm-T-induced facilitation, but did not alter the number of animals displaying erection (although the number of erections displayed by testosterone-treated rats was reduced) in ex copula tests. Treatment of castrated rats with 5 mm T, but not morphine alone, nor the combination of 5 mm T plus morphine, significantly reduced dopamine and DOPAC levels in the MBH. In the POA-AH, 5 mm T was without effect, whereas morphine, alone or in combination with 5 mm T, reduced the levels of dopamine and DOPAC. These data suggest that (1) the decline in sexual behavior induced by chronic morphine is primarily due to a failure of sexual arousal, and not of erectile ability, and (2) although the decline in sexual activity seen after castration is associated with alterations in dopaminergic metabolism, the effects of morphine and testosterone on sexual activity are opposite and dissociated from alterations in dopaminergic metabolism.     

Neuropeptide Y enhances the release of luteinizing hormone (LH) induced by LH-releasing hormone

Depending upon the steroid hormonal milieu, centrally administered neuropeptide Y (NPY) exerts differential effects on the release of LH. Ovarian hormones also effect the concentrations of NPY in hypothalamic nuclei, and some of the changes are similar to those caused by LHRH. The present studies tested whether NPY acts directly on the pituitary gland, either alone or in combination with LHRH, to modify LH secretion. Hemipituitary fragments obtained from ovariectomized rats were incubated in medium 199, and the in vitro effects on LH release of LHRH, NPY, or the two peptides together were assessed. As expected, LHRH (10(-9)-10(-7) M) produced a dose-dependent release of LH, whereas NPY alone had a lesser stimulatory effect at concentrations of 10(-7) or 10(-6) M. On the other hand, 10(-6) M NPY significantly enhanced LH release in response to 10(-9) M LHRH. A potentiation by NPY of the LHRH-induced LH response was observed in an anterior pituitary cell culture system. Cells from the pituitaries of ovariectomized rats were dispersed and cultured for 3 days in medium 199 with BSA, gentamicin, horse serum, and fetal calf serum. During a 3-h incubation, NPY alone (10(-9)-10(-7) M) failed to affect LH release, but significantly potentiated the release induced by 10(-9) or 10(-8) M LHRH. These findings are in accord with the hypothesis that hypothalamic NPY neurons may participate in the regulation of LH secretion in the rat and indicate that one of the mechanisms of its action may be to increase the pituitary LH response to LHRH.     

The role of inheritance and environment in predisposition to vascular disease in people of African descent.

OBJECTIVES: This study sought to compare vascular reactivity and carotid intima media thickness (CIMT) between Afro-Caribbean people in the United Kingdom (UK) and the West Indies and Afro-Caribbean and Caucasian people in the UK. BACKGROUND: Attenuated vascular reactivity and increased CIMT in black patients is seen as evidence for predisposition to vascular disease, but no comparisons exist between Afro-Caribbean people in different settings, which can provide insight into non-inherited determinants of increased ethnic susceptibility. METHODS: A representative community sample of 81 healthy Afro-Caribbean people and 101 Caucasian people in the UK was compared with 197 matched Afro-Caribbean people in Jamaica. Small vessel reactivity was assessed by measuring the absolute change from baseline in the reflection index (RI) of the digital volume pulse during intravenous infusion of albuterol (5 microg/min, DeltaRI(ALB)) and glyceryl trinitrate (5 microg/min, DeltaRI(GTN)). The CIMT was measured ultrasonographically in the distal 1 cm of the common carotid artery. RESULTS: Mean DeltaRI(ALB) was 4.2 percentage points (95% confidence interval [CI], 2.3 to 6.1, p < 0.001) lower in UK Afro-Caribbean people compared with Jamaican Afro-Caribbean people and 2.6 percentage points (95% CI, 0.4 to 4.7, p = 0.02) lower compared with Caucasian people, after adjusting for vascular risk profile. Adjusted mean CIMT of UK Afro-Caribbean people was 0.13 mm (95% CI, 0.08 to 0.17, p < 0.001) greater compared with Jamaican Afro-Caribbean people and 0.05 mm (95% CI, 0.01 to 0.10, p = 0.02) greater compared with Caucasian people. CONCLUSIONS: Healthy UK Afro-Caribbean people have greater and Jamaican Afro-Caribbean people have less impairment of vascular reactivity and intima media thickness compared with UK Caucasian people, suggesting that potentially modifiable environmental interactions may contribute to excess vascular disease in Afro-Caribbean people.     

Can mitral regurgitation after balloon dilatation of the mitral valve be predicted?

OBJECTIVE--To determine which factors predict the occurrence of mitral regurgitation after balloon dilatation of the mitral valve for rheumatic stenosis. DESIGN--Analysis of a case series of patients with rheumatic mitral valve stenosis who had had successful balloon dilatation of the mitral valve. SETTING--A tertiary care centre with an experience of over 150 balloon dilatations of the mitral valve. PATIENTS--70 young patients with non-calcified rheumatic mitral stenosis, who had undergone successful balloon dilatation of the mitral valve. No patient had mitral regurgitation or atrial fibrillation before dilatation. INTERVENTION--Dilatation of the mitral valve by the transvenous, transatrial double balloon technique. MAIN OUTCOME MEASURE--Development of mitral regurgitation after balloon dilatation of the mitral valve and its relation to age, mitral valve area before dilatation and after dilatation, the degree of mitral subvalvar pathology, and the size of balloon used for dilatation. RESULTS--In 10 patients (14%) mitral regurgitation developed after balloon dilatation of the mitral valve. No statistically significant differences were found between patients who did not develop regurgitation and those who did in terms of age (mean (SD)) (19.9 (6.46) v 19.4 (5.5)), mitral valve area before dilatation (1.05 (0.33) v 0.94 (0.4) cm2) and after dilatation (2.52 (1.06) v 2.45 (1.1) cm2), mitral subvalvar pathology assessed by the mitral subvalvar distance ratio (0.116 (0.03) v 0.118 (2.32), or balloon diameter corrected for body surface area (21.37 (3.5) v 20.57 (2.32) mm/m2. CONCLUSIONS--In this subset of children and young adults with non-calcified mitral stenosis, none of the morphological, technical, or patient characteristics studied predicted the development of mitral regurgitation after balloon dilatation. The low incidence of mitral regurgitation may have reduced the discriminatory power of this study. None the less, the means and standard deviation for each factor in each group suggest that even in a larger sample size the variables would have little predictive capacity.     

Humoral immune function in pediatric patients treated with autologous bone marrow transplantation for B cell non-Hodgkin's lymphoma. The influence of ex vivo marrow decontamination with anti-Y 29/55 monoclonal antibody and complement

Elimination of neoplastic B cell populations from autologous bone marrow grafts also removes normal B lymphocytes. This is potentially hazardous for the reconstitution of the immune system in patients undergoing high-dose chemotherapy and total body irradiation followed by autologous marrow rescue. Five pediatric patients with B cell non- Hodgkin's lymphoma in first remission undergoing such a regimen were studied. They received bone marrow pretreated with anti-Y 29/55 monoclonal antibody and complement. B and T lymphocyte subpopulations reached normal levels within 6 months after autologous bone marrow transplantation (ABMT), and serum immunoglobulin levels became normal within 4 to 9 months. Vaccination with diphtheria and tetanus toxoid, trivalent poliomyelitis vaccine of the Salk type, and pneumococcal capsular antigens (38 to 54 months after transplantation) gave rise to specific antibody production. ABO isoagglutinins could be demonstrated in all patients. The response pattern was similar to that of patients who received unmanipulated autologous bone marrow. It is concluded that ex vivo anti-Y 29/55 depletion of the marrow graft does not induce relevant disturbances of humoral immune functions.     

RSSDI-ESI Clinical Practice Recommendations for the Management of Type 2 Diabetes Mellitus 2020

International Journal of Diabetes in Developing Countries -     

Diagnosis and management of Neuro-Behçet’s disease: international consensus recommendations

Neuro-Behçet’s disease (NBD) is one of the more serious manifestations of Behçet’s disease (BD), which is a relapsing inflammatory multisystem disease with an interesting epidemiology. Though NBD is relatively uncommon, being potentially treatable, neurologists need to consider it in the differential diagnosis of inflammatory, infective, or demyelinating CNS disorders. Evidence-based information on key issues of NBD diagnosis and management is scarce, and planning for such studies is challenging. We therefore initiated this project to develop expert consensus recommendations that might be helpful to neurologists and other clinicians, created through an extensive literature review and wide consultations with an international advisory panel, followed by a Delphi exercise. We agreed on consensus criteria for the diagnosis of NBD with two levels of certainty in addition to recommendations on when to consider NBD in a neurological patient, and on the use of various paraclinical tests. The management recommendations included treatment of the parenchymal NBD and cerebral venous thrombosis, the use of disease modifying therapies, prognostic factors, outcome measures, and headache in BD. Future studies are needed to validate the proposed criteria and provide evidence-based treatments.     

Radiation Dose Reduction in Pediatric Cardiac Computed Tomography: Experience from a Tertiary Medical Center

Cardiac CT angiography (cCTA) has become an established method for the assessment of congenital heart disease. However, the potential harmful effects of ionizing radiation must be considered, particularly in younger, more radiosensitive patients. In this study, we sought to assess the temporal change in radiation doses from pediatric cCTA during an 8-year period at a tertiary medical center. This retrospective study included all patients ≤18 years old who were referred to electrocardiography (ECG)-gated cCTA for the assessment of congenital heart disease or inflammatory disease (Kawasaki disease) from November 2004 to September 2012. During the study period, 95 patients were scanned using 3 different scanner models—64-slice multidetector CT (64-MDCT) and first- (64-DSCT) and second-generation (128-DSCT) dual-source CT—and 3 scan protocols—retrospective ECG-gated helical scanning (RG), prospective ECG-triggered axial scanning (PT), or prospective ECG-triggered high-pitch helical scanning (HPH). Effective dose (ED) was calculated with the dose length product method with a conversion factor (k) adjusted for age. ED was then compared among scan protocols. Image quality was extracted from clinical cCTA reports when available. Overall, 94 % of scans were diagnostic (80 % for 64-slice MDCT, 93 % for 64-slice DSCT, and 97 % for 128-slice DSCT).With 128-DSCT, median ED (1.0 [range 0.6–2.0] mSv) decreased by 85.8 % and 66.8 % compared with 64-MDCT (6.8 [range 2.9–13.6] mSv) and 64-DSCT (2.9 [range 0.9–4.1] mSv), respectively. With HPH, median ED (0.9 [range 0.6–1.8] mSv) decreased by 59.4 % and 85.4 % compared with PT (2.2 [range 0.9–3.4] mSv) and RG (6.1 [range 2.5–10.6] mSv). cCTA can now be obtained at very low radiation doses in pediatric patients using the latest dual-source CT technology in combination with prospective ECG-triggered HPH acquisition.