Norepinephrine modulates glutamatergic transmission in the bed nucleus of the stria terminalis.

The bed nucleus of the stria terminalis (BNST) and its adrenergic input are key components in stress-induced reinstatement and maintenance of drug use. Intra-BNST injections of either beta-adrenergic receptor (beta-AR) antagonists or alpha2-adrenergic receptor (alpha2-AR) agonists can inhibit footshock-induced reinstatement and maintenance of cocaine- and morphine-seeking. Using electrophysiological recording methods in an in vitro slice preparation from C57/Bl6j adult male mouse BNST, we have examined the effects of adrenergic receptor activation on excitatory synaptic transmission in the lateral dorsal supracommissural BNST (dBNST) and subcommissural BNST (vBNST). Alpha2-AR activation via UK-14,304 (10 microM) results in a decrease in excitatory transmission in both dBNST and vBNST, an effect predominantly dependent upon the alpha2A-AR subtype. Beta-AR activation via isoproterenol (1 microM) results in an increase in excitatory transmission in dBNST, but not in vBNST. Consistent with the work with receptor subtype specific agonists, application of the endogenous ligand norepinephrine (NE, 100 microM) elicits two distinct effects on glutamatergic transmission. In dBNST, NE elicits an increase in transmission (62% of dBNST NE experiments) or a decrease in transmission (38% of dBNST NE experiments). In vBNST, NE elicits a decrease in transmission in 100% of the experiments. In dBNST, the NE-induced increase in synaptic transmission is blocked by beta1/beta2- and beta2-, but not beta1-specific antagonists. In addition, this increase is also reduced by the alpha2-AR antagonist yohimbine and is absent in the alpha2A-AR knockout mouse. In vBNST, the NE-induced decrease in synaptic transmission is markedly reduced in the alpha2A-AR knockout mouse. Further experiments demonstrate that the actions of NE on glutamatergic transmission can be correlated with beta-AR function.     

Psychotic symptoms and disorders and the risk of violent behaviour in the community

This study uses data from the Epidemiologic Catchment Area (ECA) surveys to examine the strength of the association between psychotic symptoms and violent behaviour, controlling for underlying mental disorder, substance abuse, sociodemographic characteristics and use of mental health services, in a representative sample of community residents. A replication is conducted of a study that found an increased risk of violence associated with a particular cluster of psychotic symptoms involving perceived threat and internal control-override (TCO). Respondents who reported TCO symptoms were about twice as likely to engage in assaultive behaviour as those with hallucinations or other psychotic symptoms, and about five times as likely as those with no mental disorder. The combination of substance use disorders with TCO symptoms added significantly to the risk of violent behaviour. Those with a history of using mental health services also posed a higher risk of violence, probably due to the differential selection of more severely ill and ‘dangerous’ individuals into treatment settings. Copyright © 1996 Whurr Publishers Ltd.     

An Integrated Psychotherapy Approach to the Management of Self-Destructive Behavior in Eating Disorder Patients with Borderline Personality Disorder

The management of self-destructive behavior in eating disorder patients with borderline personality is a genuine therapeutic challenge. We present an integrated psychotherapy appproach that we utilize in the context of an extended therapeutic milieu. This treatment model enables coordinated intervention to occur in three different arenas: individual psychotherapy, group psychotherapy, and consultation intervention. The paper closes with a discussion of the limitations of this approach.     

Simultaneous over-expression of insulin-like growth factor-II (IGF II) and IGF-II receptor (IGF-II R) genes in human primary cancer-implication of autocrine and paracrine mechanism in autonomous growth of hepatic cancer

This is first report about the simultaneous over-expression of both Insulin-like growth factor (IGF-II) and its receptor (IGF-II R) at mRNA level in human primary hepatic Cancer (PHC). In 10 PHC samples from China, IGF-II and IGF-II R were both over-expressed, whereas only a background signal was detected in normal liver. In 5 pairs of PHC and its non-tumorous adjacent liver tissues from South Africa, IGF-II and IGF-II R were also over-expressed in PHC. mRNA expression of IGF-II in all 5 cases and IGF-II R in 4 of 5 cases were higher in cancer than non-tumorous adjacent liver tissues. These results strongly implicate that an autocrine and/or paracrine mechanism might be involved in formation and progression of PHC.     

Resistance exercise training and alendronate reverse glucocorticoid-induced osteoporosis in heart transplant recipients.

BACKGROUND: Immunosuppression therapy with bolus glucocorticoids causes regional osteoporosis in the axial skeleton of heart transplant recipients (HTR). No preventive strategy is generally accepted for steroid-induced bone loss. METHODS: To determine the efficacy of an anti-osteoporosis regimen that combined a bisphosphonate agent (alendronate sodium) with the osteogenic stimulus of mechanical loading, 25 HTRs were randomly assigned either to a group that received alendronate (10 mg/day) for 6 months (ALEN; n = 8), a group that received alendronate (10 mg/day) and performed specific resistance exercises for 6 months (ALEN + TRN; n = 8) or to a non-intervention control group (CONTR; n = 9). Alendronate was initiated at 2 months after transplantation. Bone mineral density (BMD) of the total body, femur neck and lumbar spine (L-2 and L-3) was measured by dual-energy X-ray absorptiometry before and 2, 5 and 8 months after transplantation. Resistance training consisted of lumbar extension exercise (MedX) performed 1 day/week and 8 variable resistance exercises (MedX) performed 2 days/week. RESULTS: Pre-transplantation BMD values did not differ among the 3 groups. BMD of the total body, femur neck and lumbar vertebra were significantly decreased below baseline at 2 months after transplantation in CONTR (-2.6 +/- 0.9%, -5.1 +/- 1.8%, -12.5 +/- 4.2%, respectively), ALEN (-2.8 +/- 0.8%, -5.3 +/- 1.6%, -12.0 +/- 3.9%) and ALEN + TRN groups (-2.7 +/- 1.0%, -5.6 +/- 2.1%, -11.2 +/- 3.7%). CONTR had further significant losses of BMD after 3 and 6 months. ALEN had no further regional BMD losses after initiation of alendronate therapy. ALEN + TRN restored BMD of the whole body, femur neck and lumbar vertebra to within 0.9%, 2.1%, and 3.4% of pre-transplantation levels, respectively. CONCLUSIONS: Resistance exercise plus alendronate was more efficacious than alendronate alone in restoring BMD in HTRs. Our results indicate that anti-osteoporosis therapy in this population should include both an anti-resorptive agent as well as an osteogenic stimulus, such as mechanical loading.     

A methodological approach to the classification of dermoscopy images.

In this paper a methodological approach to the classification of pigmented skin lesions in dermoscopy images is presented. First, automatic border detection is performed to separate the lesion from the background skin. Shape features are then extracted from this border. For the extraction of color and texture related features, the image is divided into various clinically significant regions using the Euclidean distance transform. This feature data is fed into an optimization framework, which ranks the features using various feature selection algorithms and determines the optimal feature subset size according to the area under the ROC curve measure obtained from support vector machine classification. The issue of class imbalance is addressed using various sampling strategies, and the classifier generalization error is estimated using Monte Carlo cross validation. Experiments on a set of 564 images yielded a specificity of 92.34% and a sensitivity of 93.33%.     

The nucleotide: DNA sequencing and its clinical application.

Information determining cellular structure and function is contained in chromosomal DNA. Genes, regions of DNA encoding this information, are composed of specific sequences of nucleotides. DNA sequencing methods have been developed to identify these sequences. Even subtle alteration (or mutation) of these sequences can lead to many human syndromes and diseases. This article reviews 1) the structure of the nucleotide, 2) the methods of DNA sequencing, and 3) its recent clinical application in analysis of the nevoid basal cell carcinoma syndrome.