Predictive signs and indicators of aggressiveness and violence: a comparison between a group of adolescents attending an external penal area, a group of prisoners and a group of patients with borderline personality disorder.

AIM: Aggressive and violent behaviours in juveniles and young adults have become increasingly widespread. Most such behaviours have 2 common roots: lack of actual motivation and brutality. The most reliable indicators and predictive signs have been linked to structural personality features (e.g. defensive strategies, impulse control). With this cross-sectional study we wanted to determine specific indicators and predictive signs of violent and aggressive behaviours in these population segments. METHODS: We compared the structural personality features of 3 groups: one with 26 male adolescents with conduct disorder (F91.8), one with 29 male patients with borderline personality disorder (F60.31) and one with 34 male prisoners with antisocial personality disorder (F60.2). The test battery included: the ''Structured clinical interview for DSM-IV axis II disorders'' (for the recruitment of adult groups); the ''Indicators of aggressive conduct'' and the ''Profile of mood states'' (for the recruitment of the adolescent group); the ''Defense mechanisms inventory'' (DMI). RESULTS: The predominant defensive strategies and starting emotional backgrounds differed significantly among the groups. A profile of low emotional response was found to support aggressiveness, while a profile of aggressiveness and violence was associated with clinically significant impulsivity. CONCLUSIONS: Several indicators and clinical predictors of aggressiveness and violence, as well as high-risk-profiles, may be determined using these instruments.

Late reopening of an occluded infarct related artery improves left ventricular function and long term clinical outcome.

OBJECTIVE: To assess effects on left ventricular (LV) function and on long term clinical outcome of late percutaneous transluminal coronary angioplasty (PTCA) of a chronically occluded infarct related artery. METHODS: 65 patients who underwent PTCA a mean (SD) of 6.0 (1.2) months after a previous myocardial infarction were divided in two groups according to dilated artery patency status after PTCA: group 1 (35 patients with TIMI (thrombolysis in myocardial infarction) grade 3 flow) and group 2 (30 patients with TIMI grade 0-2 flow). Echocardiography was performed at admission and at six months' follow up. A three year follow up was conducted with major adverse cardiac events (MACE) as end points. RESULTS: At follow up, group 1 had improved global LV ejection fraction (48.7% v 43.6%, p < 0.001) and LV indexed end diastolic and end systolic volumes (75 v 86 ml/m(2) and 40 v 53 ml/m(2), respectively, p = 0.011) compared with group 2. Kaplan-Meier analysis showed a higher incidence of cardiac death (p = 0.02) and MACE (p < 0.0001) in group 2. TIMI 3 after PTCA was an independent predictor of event-free survival at follow up. CONCLUSION: Late PTCA of a chronically occluded infarct related artery improves LV function, reduces cardiac death, and improves long term clinical outcome.

Effect of aldose reductase inhibitor (tolrestat) on urinary albumin excretion rate and glomerular filtration rate in IDDM subjects with nephropathy.

OBJECTIVE: To explore the possible link between diabetic nephropathy and the enhanced activity of the polyol pathway, known to occur in IDDM subjects. RESEARCH DESIGN AND METHODS: We studied the effects of the aldose reductase inhibitor tolrestat (200 mg/day) on urinary albumin excretion rate and glomerular filtration rate in 20 IDDM patients with diabetic nephropathy. RESULTS: Six months of placebo treatment produced no significant changes in glomerular filtration rate, urinary albumin excretion rate, and renal plasma flow. Consequently, filtration fraction remained unchanged. During tolrestat treatment, glomerular filtration rate decreased from the basal value of 156 +/- 14 ml.min-1.1.73 m2 to 142 +/- 13.7 ml.min-1.1.73 m2 (P < 0.001) at 2 mo; 128 +/- 12.4 ml.min-1.1.73 m2 (P < 0.001) at 4 mo; and 123.7 +/- 13.0 ml.min-1.1.73 m2 at 6 mo. A significant decrease of urinary albumin excretion rate was observed during the trial (basal values 219 +/- 32.5 vs. 196.9 +/- 28.5 micrograms/min at 2 mo [P < 0.05]; 171.6 +/- 25.5 micrograms/min at 4 mo [P < 0.001]; and 58.6 +/- 19.3 micrograms/min at 6 mo [P < 0.001]). No significant change in renal plasma flow was seen during tolrestat treatment. Filtration fraction significantly decreased in the tolrestat group from the basal value of 0.23 +/- 0.02 to 0.21 +/- 0.01 at 2 mo (P < 0.005); 0.18 +/- 0.02 at 4 mo (P < 0.001); and 0.17 +/- 0.02 at 6 mo (P < 0.001). CONCLUSIONS: The polyol pathway is implicated in hemodynamic changes associated with early diabetic nephropathy, and aldose reductase treatment can positively influence these parameters.

Effects of mild-to-moderate hyperglycaemia per se on glucose production and uptake in the elderly.

OBJECTIVES: In order to better understand the mechanisms responsible for the diminished glucose tolerance that occurs in the elderly, the present study aimed at investigating the effect of mild hyperglycaemia on glucose production and uptake in a group of aged subjects. For comparison, a group of young subjects was simultaneously investigated. METHODS: Seven aged (71.8 +/- 2.3 yrs) and seven young (25.5 +/- 1.7 yrs) healthy non-obese subjects underwent two hyperglycaemic glucose-clamps having as targets plasma glucose levels 7.5 and 10.0 mmol/L. Contemporary infusion of D-[3-3H]-glucose allowed determination of glucose turnover parameters in basal conditions and during the clamps. Endogenous pancreatic secretion was inhibited by somatostatin (8.3 micrograms/min) while glucagon (67 ng/min) and insulin (0.15 mU/kg/min) were replaced by exogenous infusions. RESULTS: In basal conditions, glucose uptake (12.9 +/- 0.5 vs 14.4 +/- 0.4 mumol/kg/min; p < 0.05) and glucose metabolic clearance rate (2.58 +/- 0.15 vs 3.35 +/- 0.10 ml/kg/min; p < 0.01) were lower in elderly vs young subjects. In the hyperglycaemic glucose-clamps, we observed, in the elderly subjects, the persistence of a greater glucose production during mild (7.5 mmol/L) (11.6 +/- 0.4 vs 9.7 +/- 0.2 mumol/kg/min; p < 0.005) but not moderate (10 mmol/L) (3.5 +/- 0.1 vs 3.4 +/- 0.1 mumol/kg/min; NS) hyperglycaemia. In contrast, glucose-induced glucose uptake and glucose metabolic clearance rate were similarly affected by glucose infusions in both groups of subjects. Moreover, in elderly but not in young subjects, basal glucose disappearance rate was significantly negatively correlated with fasting plasma glucose levels (r = -0.84; p < 0.01). CONCLUSIONS: In the basal state, glucose uptake and glucose metabolic clearance rate are slightly impaired in elderly, compared to young subjects. Furthermore, in the elderly, endogenous glucose production is less suppressed by mild hyperglycaemia i.e. 7.5 mmol/L, than it is in young people. Such impairment in the inhibition of endogenous glucose production is not seen when blood glucose attains 10 mmol/L. We suggest that impairment in glucose tolerance in the elderly results from both reduced glucose uptake (in basal conditions) and excessive glucose production (at mild hyperglycaemic levels).

Metabolic and cardiovascular benefits deriving from beta-adrenergic blockade in chronic congestive heart failure.

Ten patients with congestive heart failure were given metoprolol (50 mg/day) or placebo during a double-blind, crossover, randomized study. After a run-in period of 4 weeks, metoprolol and placebo were administered over a period of 3 months, which was separated by a washout period of 4 weeks. At the end of the run-in, metoprolol, and placebo periods, all patients underwent metabolic (oral glucose tolerance and hyperinsulinemic glucose clamp tests) and noninvasive cardiologic (New York Heart Association classification, bimodal echocardiographic left ventricular end-diastolic determination, maximal oxygen consumption, left ventricular radionuclide ejection fraction) tests. Our results show that beta-adrenergic blockade significantly enhances insulin-mediated suppression of hepatic glucose output (p less than 0.005) and increase in glucose uptake (p less than 0.01) with a concurrent improvement in New York Heart Association functional class (p less than 0.05) and the multistage exercise treadmill test score (p less than 0.05). After administration of metoprolol all changes in glucose turnover parameters were found to correlate with the decrease in basal plasma free fatty acid levels. In conclusion, our findings confirm the beneficial cardiologic effects of beta-adrenergic blockade in congestive heart failure and demonstrate that metoprolol is also useful for reversing the metabolic damage caused by exaggerated plasma norepinephrine levels.

Evidence for peripheral impaired glucose handling in patients with connective tissue diseases.

Sixteen patients suffering from rheumatoid arthritis (RA) (n = 8), systemic lupus erythematosus (SLE) (n = 5), and systemic sclerosis (SSc) (n = 3), and 10 healthy subjects matched for age, sex, and body mass index, were submitted to an intravenous (IV) glucose tolerance test (GTT) (0.33 g/kg of body weight in 3 minutes) and to a euglycemic hyperinsulinemic glucose clamp to study insulin response and action. In the euglycemic clamp, along with the two insulin infusion rates (0.5 mU/kg.min from 0 to 120 minutes and 1 mU/kg.min from 121 to 240 minutes), a primed (20 microCi) continuous (0.2 microCi/min) infusion of 3H-glucose allowed determination of glucose kinetics. Our data show that patients versus controls have (1) a significant increase in basal plasma insulin levels (87.2 +/- 14.8 v 41.3 +/- 6.0 pmol/L, P less than .05); (2) similar glucose-induced acute insulin response; and (3) a lower glucose disappearance rate (Rd), glucose metabolic clearance rate (gMCR), and glucose infusion rate (GIR) when the lowest insulin infusion rate was delivered. These differences disappeared when the insulin infusion rate was doubled. Furthermore, basal plasma insulin levels and glucose disappearance rate significantly correlated with the main inflammatory indices of each disease studied. We conclude that in our patients impaired glucose handling is mainly due to peripheral insulin resistance.

Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failure.

Congestive heart failure is a condition associated with increased plasma norepinephrine levels. Moreover, norepinephrine has been recently demonstrated to affect glucose homeostasis by decreasing insulin sensitivity. In the present study, eight patients suffering from chronic congestive heart failure and 10 healthy age- and body mass index-matched subjected were submitted to both an oral glucose tolerance test (OGTT; 75 g) and a euglycemic hyperinsulinemic glucose clamp. During the 360 minutes of the glucose clamp, insulin was infused at three different rates (25, 50, and 100 mU/kg/h), while D-3H glucose infusion allowed determination of glucose turnover. In basal conditions, patients versus controls had similar plasma glucose (5.2 +/- 0.1 v 4.9 +/- 0.2 mmol/L,P = NS), but higher plasma insulin (125.7 +/- 9.2 v 35.7 +/- 3.3 pmol/L,P less than .01), norepinephrine (5.39 +/- 0.13 v 1.47 +/- 0.22 nmol/L,P less than .001), and free fatty acid (FFA) (927 +/- 79 v 792 +/- 88 mumol/L,P less than .05) levels. In patients, basal plasma norepinephrine correlated with FFA levels (r = .65, P less than .025). After loading glucose, plasma glucose and insulin levels were still significantly higher in patients than controls. Euglycemic hyperinsulinemic glucose clamp produced a lower insulin-mediated inhibition of endogenous (hepatic) glucose production (HGP) and a greater increase in both glucose disappearance rate (Rd) and glucose metabolic clearance rate (gMCR) in patients than in controls during the first two insulin infusion rates (25 and 50 mU/kg/h). By contrast, these differences disappeared during the highest insulin infusion rate (100 mU/kg/h). Insulin-mediated decrease in plasma FFA levels was also lower in patients than controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of oxytocin upon the endocrine pancreas secretion and glucose turnover in normal man.

In normal man oxytocin infusion under basal conditions and at pharmacological doses evoked a rapid surge in plasma glucose and glucagon levels followed by a later increase in plasma insulin levels. Simultaneous [D-3H]glucose infusion indicated that oxytocin also produced a prompt and significant increase in hepatic glucose output with a secondary increase in glucose disappearance rate. Eight healthy volunteers were studied during euglycemic glucose clamp and simultaneous [D-3H]glucose infusion, during suppression of endogenous pancreatic secretion by cyclic somatostatin (250 micrograms/h) and during exogenous glucagon (67 ng/min) and insulin (0.15 mU.kg-1.min-1 from 0 to 120 min and 0.40 mU.kg-1.min-1 from 121 to 240 min) replacement. During the first 60 min oxytocin (0.2 U/min) evoked a transient but significant increase in plasma glucose levels and hepatic glucose output with a simultaneous suppression of the glucose infusion rate. No difference in glucose disappearance and metabolic clearance rates were recorded throughout the clamp irrespective of whether oxytocin was infused or not. So we conclude that oxytocin exerts a hyperglycemic effect through an A-cell stimulation and a glycogenolytic action.

Characteristics of insulin resistance in Turner syndrome.

The characteristics of insulin resistance, in Turner syndrome are still unclear. For this purpose in 4 patients with Turner syndrome and in 8 control females we performed an euglycaemic hyperinsulinemic glucose clamp at the following insulin infusion rates (50 and 100 mU/Kg x h), each period lasting 120 min. A simultaneous infusion of D-3-H-glucose allowed us to determine in basal conditions and during the clamp hepatic glucose output and glucose disappearance rate (Rd). In basal conditions plasma glucose (4.8 +/- 0.1 vs 4.6 +/- 0.2 mmol/1 p = NS) and plasma glucagon (102 +/- 7.5 vs 112 +/- 11.3 ng/l p = NS) were similar in both groups despite higher plasma insulin (19 +/- 1.8 vs 7 +/- 2.2 mU/l p less than 0.05) and C-peptide (1.0 less than 0.1 vs 0.8 +/- 0.06 pmol/l p less than 0.05) levels in patients with Turner syndrome. In the last 60 min of the lower insulin infusion rate glucose infusion rate (4.1 +/- 0.3 vs 2.9 +/- 0.4 mg/Kg x min p less than 0.05) and glucose disappearance rate (3.89 +/- 0.12 vs 2.63 +/- 0.11 mg/Kg x min p less than 0.01) were significantly reduced in patients with Turner. On the contrary hepatic glucose output was similarly suppressed in both groups of subjects. Doubling the insulin infusion rate, we obtained similar results in patients and controls respectively. So we conclude that in Turner syndrome the insulin resistance state is mainly due to a muscular receptor defect.

Impaired insulin-mediated erythrocyte magnesium accumulation is correlated to impaired insulin-mediated glucose diposal in aged non-diabetic obese patients.

Basal erythrocyte magnesium levels were significantly lower in obese than lean subjects. In vitro incubation in the presence of 100 mU/l insulin significantly increased magnesium erythrocyte levels in both groups of subjects. However, even in the presence of 100 mU/l, the erythrocyte magnesium content of obese patients was lower than that of control subjects. The in vitro dose-response curve of the effect of insulin on magnesium erythrocyte accumulation was shifted to the right when the red cells of obese were used, with a highly significant reduction of the maximal effect. Such reduction of the maximal effect of insulin suggests that the impairment of insulin-induced erythrocyte magnesium accumulation observed in obese patients results essentially from a post-receptor defect. In obese patients, net increase in erythrocyte magnesium levels (calculated as the difference between basal and 100 mU/l insulin-induced erythrocyte magnesium levels) was negatively correlated with basal plasma insulin levels (r = 0.79 p less than 0.01), and with body mass index (r = 0.81 p less than 0.01) while it was positively correlated with the glucose disappearance rate after glucose load (r = 0.67 p less than 0.05) and glucose metabolic clearance rate (r = 0.71 p less than 0.01). These results demonstrate that insulin-induced erythrocyte magnesium accumulation is impaired in patients with obesity and that such defect is correlated to impaired -- mediated glucosal disposal in the patients.

Insulin resistance as cause of increased blood pressure in the elderly: effects on intracellular ion contents.

Previous reports have evidenced a strong relationship between high plasma insulin levels and blood pressure in diabetic and obese subjects but not in the elderly. During aging many patho-physiological changes in cardiovascular functions and autonomic nervous system occur, so that aging per se might be a cause of a 'physiological' increase in blood pressure. Nevertheless, an insulin resistance also develops during aging. The present study investigates the possible role of age-dependent insulin resistance in the genesis of increased blood pressure. Our data show that insulin resistance calculated by the glucose infusion rate during a euglycemic hyperinsulinemic glucose clamp procedure is significantly correlated with the insulin-mediated net decrease in erythrocyte Na+ content (r = 0.58, P < 0.05), as well as with net increase in erythrocyte K+ (r = 0.64, P < 0.05) and Mg2+ (r = 0.67, P < 0.01) content and to basal diastolic blood pressure (r = -0.63, P < 0.05). We conclude that in elderly subjects the age-related and normally occurring insulin resistance might contribute to the increase of arterial blood pressure through its effect on cell cation content.

Dietary magnesium supplements improve B-cell response to glucose and arginine in elderly non-insulin dependent diabetic subjects.

Hypomagnesemia and low erythrocyte magnesium content are both common findings in non-insulin-dependent diabetic subjects. Moreover, intracellular magnesium may play a crucial role in modulating B-cell response to glucose by interfering with potassium permeability. Eight elderly, moderately obese, non-insulin-dependent diabetic subjects were treated with either magnesium supplementation (3 g/day) to the diet or placebo. Both treatment schemes lasted 4-weeks and were separated by a 'wash-out' of 3 weeks. At the end of each treatment period, in glucose test (0.33 g/kg for 3 min) and an iv arginine (5 g) test were performed to determine the B-and A-cell responses. Dietary magnesium supplementation vs placebo produced a slight but significant decrease in basal plasma glucose (8.6 +/- 0.3 vs 8.0 +/- 0.1 mmol/l, p less than 0.05) and an increase in acute insulin response after iv glucose (3.7 +/- 2.3 vs - 14.7 +/- 0.9 pmol.l 1. (10 min)-1, p less than 0.01) and after iv arginine (151 +/- vs 81 +/- 15 pmol.l-1. (10 min)-1, p less than 0.01), respectively. Plasma glucagon levels were unaffected by chronic dietary magnesium supplementation as well under basal conditions as in response to arginine. Net increase in acute insulin response after iv glucose and after iv arginine was significantly correlated to the net increase in erythrocyte magnesium content after dietary magnesium supplementation. We conclude that magnesium administration may be a useful adjuvant to the classic hypoglycemic agents in the treatment of non-insulin-dependent diabetic subjects.

Lack of diabetogenic action of calcitonin in subjects affected by insulinoma.

Calcitonin has been shown to affect calcium handling within cells thus impairing insulin secretion and glucose tolerance in healthy subjects. In the present study we investigate the effects of calcitonin on basal and nutrients-induced plasma glucose and insulin levels variations in healthy subjects (n = 10) and in patients affected by islet cell tumor (n = 6). In healthy subjects calcitonin markedly decreased basal and nutrients-induced plasma insulin levels while in patients with islet cell tumor this calcitonin-mediated effect was lost. So we conclude that the lack of calcitonin effect upon insulin secretion in patients with insulinoma is probably due to the autonomous insulin secretion characterizing islet cell tumor.