Deep brain stimulation: new directions.

The role of deep brain stimulation (DBS) in the treatment of movement disorders is well established, but there has recently been a proliferation of additional indications that have been shown to be amenable to this technology. The combination of innovative approaches to neural interface technology with novel target identification based on previously discovered clinical effects of lesioning procedures has led to a fundamental paradigm for new directions in the application of DBS. The historical use of neurosurgical lesioning procedures in the treatment of psychiatric diseases such as obsessive compulsive disorder provided an initial opportunity to expand the use of DBS. The list is rapidly expanding and now includes major depressive disorder, Tourette's syndrome, addiction disorders, and eating disorders. Keen observations by neurosurgeons using these devices have lead to the incidental discovery of treatments for diseases without previous neurosurgical treatments. These discoveries are breaking new ground in the treatment of disorders of cognition, headache syndromes, disorders of consciousness, and epilepsy. Two features of DBS make it well-suited for treatment of disorders of nervous system function. First, the reversible, non-lesional nature of DBS allows for investigation of new targets without the morbidity of permanent side effects. Second, the programmable nature of DBS allows practitioners to alter stimulation patterns to minimize side effects and potentially improve efficacy through reprogramming. More importantly, proper scientific evaluation of new targets is aided by the ability to turn stimulation on and off with evaluators blinded to the stimulation status. Knowledge of these emerging therapies is important for practitioners, as there are many situations where a single target can effectively treat the symptoms of more than one disease. The intersection of advances in neuromodulation, neurophysiology, neuroimaging, and functional neuroanatomy has created an environment rife with new therapeutic possibilities.

Influence of the PPAR-gamma2 Pro12Ala and ACE I/D polymorphisms on insulin sensitivity and training effects in healthy offspring of type 2 diabetic subjects.

Aerobic endurance training improves insulin sensitivity, and is of great importance in the prevention and treatment of type 2 diabetes. The improvement in insulin sensitivity and cardiovascular function through exercise is highly variable among individuals, and is probably partly determined by genetic components. This study evaluated the peroxisome proliferation-activated receptor-gamma2 ( PPAR-gamma2) Pro12Ala polymorphism and the angiotensin converting enzyme ( ACE) I/D polymorphism with respect to any potential influence that these highly prevalent polymorphisms may impose on changes in insulin sensitivity and maximal aerobic capacity induced by exercise. Seventy-nine healthy first-degree relatives of type 2 diabetic patients were compared to a control group consisting of 54 subjects without any family history of type 2 diabetes. All subjects had a normal OGTT. The groups were comparable with respect to age (34 +/- 7 vs. 33 +/- 7 years), gender ((m/f) 43/36 vs. 30/24) and BMI (25.7 +/- 2.6 vs. 25.3 +/- 2.5 kg/m (2)); p (all) = NS. Furthermore, a subgroup of 29 offspring and 17 control subjects were engaged in a standardized training program lasting ten weeks. Insulin sensitivity (hyperinsulinemic euglycemic clamp technique) and VO (2)max (exhaustive exercise test) was assessed before and after the training period. We will demonstrate the allelic frequency of the Ala-allele of the Pro12Ala polymorphism to be lower in offspring to type 2 diabetic patients (13.3 %) compared to control subjects (21.3 %); p < 0.05. In offspring only, the Pro12Ala polymorphism of the PPAR-gamma2 gene appeared to enhance weight changes brought about by exercise (Deltaweight = - 0.3 +/- 1.4 kg vs. - 1.8 +/- 1.8 kg; p < 0.05; (Pro/Pro vs. Pro/Ala + Ala/Ala) - suggesting possible gene-environment or gene-gene interactions. The ACE I/D polymorphism was not of significant importance in determining the capability of responding to exercise in terms of improvement in insulin sensitivity or maximal aerobic capacity.

Adiponectin expression in adipose tissue is reduced in first-degree relatives of type 2 diabetic patients.

Adiponectin is suggested to be an important mediator of insulin resistance. Therefore, we investigated the association between adiponectin and insulin sensitivity in 22 healthy first-degree relatives (FDR) to type 2 diabetic patients and 13 matched control subjects. Subcutaneous adipose tissue biopsies were taken before and after a hyperinsulinemic euglycemic clamp. FDR subjects were insulin resistant, as indicated by a reduced M value (4.44 vs. 6.09 mg x kg(-1) x min(-1), P < 0.05). Adiponectin mRNA expression was 45% lower in adipose tissue from FDR compared with controls (P < 0.01), whereas serum adiponectin was similar in the two groups (6.4 vs. 6.6 microg/ml, not significant). Insulin infusion reduced circulating levels of adiponectin moderately (11-13%) but significantly in both groups (P < 0.05). In the control group, adiponectin mRNA levels were negatively correlated with fasting insulin (P < 0.05) and positively correlated with insulin sensitivity (P < 0.05). In contrast, these associations were not found in the FDR group. In conclusion, FDR have reduced adiponectin mRNA in subcutaneous adipose tissue but normal levels of circulating adiponectin. Adiponectin mRNA levels are positively correlated with insulin sensitivity in control subjects but not in FDR. These findings indicate dysregulation of adiponectin gene expression in FDR.

[Transportation of patients with acute myocardial infarction]. / Transport af patienter med akut myokardieinfarkt.

The aim of this study was to describe the results and experiences from a local hospital concerning transports with patients with acute myocardial infarction to primary PTCA. Our material includes 27 patients who had primary PTCA. There were no complications during the transports. None of the patients had hypotension or arrythmia requiring treatment during the transports. One patient had ventricular fibrillation before the transport. None of the patients died during the transports. Two patients died in the period following PTCA. The transport delay was 1 hour and 40 minutes on average. Future randomized studies like DANAMI 2 will show if PTCA with delayed treatment, or immediate thrombolysis, give better results for the patient.