No effect on oxidative stress biomarkers by modified intakes of polyunsaturated fatty acids or vegetables and fruit.

Diet may both increase and decrease oxidative stress in the body. We compared the effects of four strictly controlled isocaloric diets with different intakes of polyunsaturated fatty acids (PUFA, 11 or 3% of energy) and vegetables and fruit (total amount of vegetables and fruit 516 or 1059 g/10 MJ) on markers associated with oxidative stress in 77 healthy volunteers (19-52 years). Plasma protein carbonyls (2-aminoadipic semialdehyde residues) and whole-body DNA and nucleotide oxidation (urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion) tended to decrease in all treatment groups with no differences between the diets. The diets did not differ in their effects on red blood cell antioxidative enzyme activities, either. The results suggest that in healthy volunteers with adequate nutrient intakes, 6-week diets differing markedly in the amount of PUFA or vegetables and fruit do not differ in their effects on markers associated with oxidative stress.

[Patients in forensic and general psychiatry. Do risk assessment measures detect differing risks of future violence?]. / Forensische Patienten und Patienten der Allgemeinpsychiatrie. Bilden Prognoseinstrumente unterschiedliche Gewalttäterrisiken ab?

BACKGROUND: The aim of this study was to assess the potential for future violent behaviour comparing patients recruited from forensic and general psychiatric wards in Germany. PATIENTS AND METHODS: Fifty patients were recruited from a forensic hospital and 29 from a general psychiatric hospital. In the weeks preceding discharge, structured assessments of the future risk of violent behaviour were completed using the HCR-20. RESULTS: There was little difference in the risk presented by the two groups. Forensic patients presented an elevated risk of violence because of historical factors, while the risk among patients from general psychiatry was due to clinical symptoms. CONCLUSION: Some criminal offences could be prevented if more time and effort were spent in general psychiatric practice in identifying patients at high risk for violence and in reducing symptoms of psychoses before discharge.

Determination of a reference value for N(G), N(G)-dimethyl-L-arginine in 500 subjects.

BACKGROUND: Asymmetric dimethylarginine (ADMA) acts as an endogenous inhibitor of NO-synthase. In the last years ADMA has emerged as a cardiovascular risk factor. The aim of this study was to determine a reference value for ADMA. METHODS: Plasma samples of 500 healthy subjects in the 19-75 year age group were analyzed. Exclusion criteria from this study were smoking, any known significant disease, body-mass-index (BMI) above 30 kg m(-2), elevated plasma lipid levels, impaired renal function, hypertension, and intake of any medication. The ADMA levels were determined by ELISA, (DLD Diagnostics, Hamburg, Germany). RESULTS: Mean ADMA plasma concentration of the total population was 0.69 micromol L(-1) (SD 0.20) and 95% of the measured values were in the range from 0.36 micromol L(-1) to 1.17 micromol L(-1). Women below 50 years of age had lower ADMA levels than men below 50 years of age [0.62 (0.17) micromol L(-1) vs. 0.69 (0.19) micromol L(-1); P = 0.001] and woman above 50 years of age had higher ADMA levels than men above 50 years of age [0.80 (0.22) micromol L(-1) vs. 0.73 (0.20) micromol L(-1); P = 0.036]. A regression analysis of ADMA levels and age was performed for each sex. The regression factor was r = 0.444 for women in a squared regression model (P < 0.001) and r = 0.212 for men in a linear regression model (P < 0.001). CONCLUSION: The study was able to define a reference value for ADMA plasma levels with 0.36-1.17 micromol L(-1) and found sex dependent correlations between ADMA and age. Women showed a significant increase in ADMA plasma levels with onset of menopause.

Affect regulation in borderline personality disorder: experimental findings from psychophysiology and functional neuroimaging.

BACKGROUND: Intense and rapidly changing mood states are a major feature of borderline personality disorder (BPD), which is thought to arise from affective vulnerability. OBJECTIVE: There have been only a few studies investigating affective processing in BPD, and particularly neither psychophysiological nor neurofunctional correlates of abnormal emotional processing have been identified so far. METHODS: Studies are reported using psychophysiological or functional neuroimaging methodology. RESULTS: The psychophysiological study did not indicate a general emotional hyperresponsiveness in BPD. Low autonomic arousal seemed to reflect dissociative states in borderline subjects experiencing intense emotions. In the functional magnetic resonance imaging study enhanced amygdala activation was found in BPD, and it is suggested to reflect the intense and slowly subsiding emotions commonly observed in response to even low-level stressors. CONCLUSIONS: Implications for psychotherapy are discussed.

Emotion in criminal offenders with psychopathy and borderline personality disorder.

BACKGROUND: Criminal offenders with a diagnosis of psychopathy or borderline personality disorder (BPD) share an impulsive nature but tend to differ in their style of emotional response. This study aims to use multiple psychophysiologic measures to compare emotional responses to unpleasant and pleasant stimuli. METHODS: Twenty-five psychopaths as defined by the Hare Psychopathy Checklist and 18 subjects with BPD from 2 high-security forensic treatment facilities were included in the study along with 24 control subjects. Electrodermal response was used as an indicator of emotional arousal, modulation of the startle reflex as a measure of valence, and electromyographic activity of the corrugator muscle as an index of emotional expression. RESULTS: Compared with controls, psychopaths were characterized by decreased electrodermal responsiveness, less facial expression, and the absence of affective startle modulation. A higher percentage of psychopaths showed no startle reflex. Subjects with BPD showed a response pattern very similar to that of controls, ie, they showed comparable autonomic arousal, and their startle responses were strongest to unpleasant slides and weakest to pleasant slides. However, corrugator electromyographic activity in subjects with BPD demonstrated little facial modulation when they viewed either pleasant or unpleasant slides. CONCLUSIONS: The results support the theory that psychopaths are characterized by a pronounced lack of fear in response to aversive events. Furthermore, the results suggest a general deficit in processing affective information, regardless of whether stimuli are negative or positive. Emotional hyporesponsiveness was specific to psychopaths, since results for offenders with BPD indicate a widely adequate processing of emotional stimuli.

High linoleic acid, low vegetable, and high oleic acid, high vegetable diets affect platelet activation similarly in healthy women and men.

Upregulation of protein kinase C (PKC), an important enzyme in platelet activation, could be one step toward platelet hyperactivity. PKC activation can be modulated by dietary components in vitro, but few data are available concerning the in vivo effects. In this strictly controlled human dietary intervention, the influence of dietary unsaturated fatty acids and vegetable compounds on platelet activation was investigated. A high linoleic acid diet (10% of energy) with small amounts of vegetables (no berries or apples) was consumed by 9 women and 4 men (24.1 +/- 3.9 y), and was compared with a high oleic acid diet (12% of energy) with considerable amounts of vegetables, berries and apples consumed by 8 women and 4 men (24.2 +/- 5.5 y). Subjects were healthy Finnish volunteers. Compliance with the experimental protocol was good, as indicated by changes in plasma fatty acids and concentrations of vitamin C, beta-carotene and alpha-tocopherol. No differences between groups were seen in indices of platelet activation, including platelet aggregation, total PKC activity and distribution of PKC isoenzymes alpha, beta(II) and delta. The results indicate that in apparently healthy and fairly young subjects with adequate vitamin intakes, diets differing markedly in their amounts of linoleic and oleic acids, and vegetables, berries and apples do not differ in platelet activation.

Fats, lipids and blood coagulation.

Saturated and n-3 fatty acids, postprandial lipaemia, and the combined effects of fatty acids and lipid-lowering drugs have been of principal interest in recent studies in the field of dietary fats, lipids and haemostasis. The sex-specific effect of individual saturated fatty acids on coagulation factor VII activity has been discovered, and the significant effect of factor VII R353Q polymorphism on the postprandial response has also been found. An increased intake of n-3 fatty acids or fat reduction when combined with intensive lifestyle interventions may lead to reduced thrombotic potential in type 2 diabetic patients and obese individuals. Furthermore, positive effects on haemostasis by combined treatment with long-chain n-3 fatty acids and simvastatin indicate that n-3 fatty acids may be of some relevance with lipid-lowering drugs. The possible unfavourable effect of n-3 fatty acids on plasminogen activator inhibitor-1 activity is still a matter of dispute, but recent studies suggest that n-3 fatty acids, including alpha-linolenic acid, may have antithrombotic effects by enhancing protein C activity.

[Impulse control and affect regulation in personality disorders]. / Impulskontrolle und Affektregulation bei Persönlichkeitsstörungen.

In borderline and antisocial personality disorder there is a close interaction between affect dysregulation and impulse control disorder. Different approaches are presented that focus on affective responses to experimental stimuli in these personality disorders. Results suggest that in borderline personality disorder intense emotional responses occur in the context of specific stressors, in particular fear of being abandoned. Evidence for a general emotional hyperreactivity was not found; on the contrary, female borderline subjects rather showed reduced emotional arousal. Regarding the psychopathic subtype of antisocial personality disorder, results provided strong support for the theory of emotional detachment, which may predispose to violence through a lack of feeling of fear or also of compassion which could counteract violent impulses. Consequences for psychotherapy in BPD are considered.

Lipid peroxidation status, somatic mutations and micronuclei in peripheral lymphocytes: a case observation on a possible interrelationship.

A controlled dietary study was conducted in healthy female volunteers and reported elsewhere [1]. In a subset of samples four different biomarkers were analyzed: plasma malondialdehyde (MDA) levels and urinary 8-isoprostaglandin-F(2alpha) were measured as markers for lipid peroxidation. The frequency of hprt (hypoxanthine guanine phosphoribosyl transferase) mutants and micronuclei in peripheral blood lymphocytes were analyzed as indicators of genotoxic effects. One of the ten individuals showed extremely high background levels in all of the four endpoints measured. This case observation raises the possibility that life style factors and dietary habits affect the level of DNA reactive lipid peroxidation products, which in turn increase mutagenic and cytogenetic effects. A possible association between these biomarkers, particularly in relation to dietary fat intake and antioxidant status, should now be studied in a larger trial.

Identification and quantification of flavonoids in human urine samples by column-switching liquid chromatography coupled to atmospheric pressure chemical ionization mass spectrometry.

A rapid and sensitive high-performance liquid chromatographic mass spectrometric (HPLC-MS) method is described for the determination and quantification of 12 dietary flavonoid glycosides and aglycons in human urine samples. Chromatographic separation of the analytes of interest was achieved by column-switching, using the first column (a Zorbax 300SB C-3 column) for sample cleanup and eluting the heart-cut flavonoid fraction onto the second column (a Zorbax SB C-18 column) for separation and detection by ultraviolet and atmospheric pressure chemical ionization MS using single ion monitoring in negative mode. The fragmentor voltage was optimized with regard to maximum abundance of the molecular ion and qualifier ions of the analytes. Calibration graphs were prepared for urine, and good linearity was achieved over a dynamic range of 2.5-1000 ng/mL. The inter- and intraassay coefficients of variation for the analysis of the 12 different flavonoids in quality control urine samples were 12.3% on average (range 11.0-13.7%, n = 24, reproducibility) and the repeatability of the assay were 5.0% (mean, range 0.1-14.8%, n = 12). A subset of 10 urine samples from a human dietary intervention study with high and low flavonoid content was analyzed, and the results are reported.

Nephron-sparing surgery for renal cell carcinoma--is tumor size a suitable parameter for indication?

OBJECTIVES: Because patients with small renal cell carcinomas (RCC) are being treated by nephron-sparing surgery with increased frequency, a generally accepted parameter giving additional information as to which kind of tumor is suitable for this treatment is urgently required. METHODS: In a retrospective analysis of 245 patients who underwent radical nephrectomy for RCC, we investigated whether tumor size could provide the necessary information. We analyzed the association of tumor size with pTNM classification, grade, and the findings of the flow cytometric analysis of the DNA content analyzing the DNA index (DI). RESULTS: Stage pT1 was found in 23 patients (9.4%), pT2 in 100 (40.8%), pT3 in 109 (44.5%), and pT4 in 13 patients (5.3%). Grade 1 was found in 87 patients (35.5%), grade 2 in 120 (49.0%), and grade 3 in 38 patients (15.5%). A low DI was found in 71%, a moderately increased DI in 20%, and a high DI in 9%. Lymph node metastases were detected in 14% and -distant metastases in 22%. Closer examination of the tumors less than 2.5 cm (n = 23) revealed a significantly lower incidence (P <0.001) of infiltration of the renal capsule (n = 0) than in the rest of the group. Positive lymph nodes or distant metastases could not be found in this subgroup. A multifocal appearance of RCC was detected in only 2 (8.7%) of the 23 patients; it was detected in 67 (30.2%) of the 222 patients in the rest of the group. None of the 23 patients had grade 3 tumors (P <0.05). Fifty-two percent of the tumors were grade 1 and 48% grade 2. None of the 23 had a high DI; a moderately increased DI was found in 1 patient and a low DI in 22 of the 23 patients. Detailed examination of the tumors between 2.5 and 4 cm (n = 29) revealed an infiltration of the renal capsule in 11 (38%); lymph node metastases were found in 2 (6.9%) and metastases in 4 (13.8%). A multifocal appearance was found in 4 (13.9%) of the 29 patients; grade 3 tumors were detected in 3 (10.3%) of 29 patients, grade 2 tumors in 12 (41.4%), and grade 1 tumors in 14 (48.3%). In this subgroup, a high DI was found in 14% (not significant). The examination of tumors larger than 4 cm in size revealed worse results in the pTNM classification, grade, and flow cytometric results. CONCLUSIONS: Only tumors smaller than 2.5 cm should be considered suitable for nephron-sparing surgery in patients eligible for elective surgery. In patients in whom nephron-sparing surgery is imperative, even tumors between 2.5 and 4 cm appear to be suitable. In patients requiring extensive resection, however, the risk of local recurrence seems to be higher because of the higher incidence of multifocality.

Cardiovascular malformations in experimental congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Newborns with congenital diaphragmatic hernia (CDH) frequently have associated anomalies that have a major impact on survival rate independent of pulmonary hypoplasia and pulmonary hypertension. Cardiovascular malformations (CVM) represent a major group of lethal extrapulmonary abnormalities that often assume greatest prognostic significance in most CDH studies. Animal models resembling human CDH may aid knowledge of the basic embryology that leads to the coexpression of CDH and CVM. This study, therefore, analyzed the incidence and spectrum of CVM in fetal rats with CDH. METHODS: Left-sided CDH (LCDH) was induced in fetal rats by the maternal administration of 100 mg of nitrofen by gavage on day 9.5 gestation (term, day 22). Control animals received olive oil (OO) and were used for comparative analysis. Fetal rats were harvested by cesarean section on day 21.5 or day 22, histologically processed and examined for CVM. RESULTS: A significant number of CVM were observed in 15 of 60 (25%) LCDH rats compared with 4 of 60 (6.7%) nitrofen non-CDH rats (P = .01). The spectrum of abnormalities in CDH included ventricular septal (VSD) defects (n = 6), vascular rings (n = 4), anomalous subclavian arteries (n = 3), atrioventricular septal defects (n = 1) and Fallot's tetralogy (n = 1). A VSD (n = 1), double-outlet right ventricle VSD (n = 1) and Fallot's tetralogy (n = 2) were noted in nitrofen non-CDH rats. Control (OO) fetal rats (n = 60) displayed no malformations. CONCLUSIONS: These results confirm a significant incidence and spectrum of CVM in a teratogenic CDH model similar to that seen in humans with CDH. The findings of this study reinforce the validity of the nitrofen model as a research tool to uncover the genetic and molecular mechanisms responsible for the genesis of CDH and allied malformations.

Green tea extract decreases plasma malondialdehyde concentration but does not affect other indicators of oxidative stress, nitric oxide production, or hemostatic factors during a high-linoleic acid diet in healthy females.

BACKGROUND: Green tea contains polyphenolic catechins which can act as antioxidants and thus decrease the risk for cardiovascular diseases. AIM OF THE STUDY: To investigate whether green tea extract differs from placebo in its effects on markers of antioxidant status, lipid peroxidation, nitric oxide production, thromboxane production, and blood coagulation during a controlled high linoleic acid diet in healthy subjects. METHODS: Twenty healthy non-smoking females (23-50 years) participated in a 4-week controlled intervention study. The experimental diet was rich in linoleic acid (9 en%) and contained fat, protein, and carbohydrates: 27, 14, and 59 en%, respectively. In addition, the subjects ingested encapsulated green tea extract (3 g/d) or placebo mixture in a double-blind manner. Fasting blood samples and five 24-hour urines were collected before and at the end of the 4-week experimental period. Same samples were received from 10 control subjects. RESULTS: Green tea extract significantly decreased plasma malondialdehyde (MDA) concentration in comparison with the placebo treatment. The treatments did not differ in serum lipids, indicators of antioxidant status, urinary 8-isoprostaglandin F2 alpha, 2,3-dinorthromboxane B2, nitric oxide metabolites or coagulation indicators. CONCLUSIONS: We conclude that an amount of green tea extract which corresponds to 10 cups of tea per day for 4 weeks does not have specific effects on several indicators related to risk of cardiovascular diseases in comparison with placebo treatment. The relatively small but significant decrease in lipid peroxidation indicated by decreased plasma MDA was not associated with changes in markers of oxidative stress (urinary 8-isoprostaglandin F2 alpha and blood oxidized glutathione) or hemostasis.

The Park Nicollet experience in establishing a hospitalist system.

A hospitalist system was developed at Park Nicollet Clinic in 1993, was implemented in 1994, and remains in existence today. It was established without knowledge of any other similar program in the United States. Internists and family practitioners were given the choice to continue to care for hospitalized patients or to become totally office based. The new system has met with good patient acceptance along with increased physician satisfaction and retention. This paper describes some key aspects of the institution of the system in a multispecialty group that includes both family practitioners and internists.

Replacement of dietary saturated by unsaturated fatty acids: effects of platelet protein kinase C activity, urinary content of 2,3-dinor-TXB2 and in vitro platelet aggregation in healthy man.

The present study was conducted to compare the effects of oleic (OA) and linoleic acids (LA) on platelet function in healthy subjects. After a 4-week period on a diet rich in saturated fatty acids (SAFA), 38 volunteers (20 female, 18 male) had a high OA (18.0 en%) diet or a high LA diet (11.5 en%) for four weeks in a controlled manner. A control group of 13 subjects consumed their habitual diet throughout the study. Replacing the SAFA diet by the OA or LA diet did not affect the membrane-associated activity of platelet protein kinase C (PKC). However, both diets tended to increase the cytosolic activity to a comparable extent. Both the OA and the LA diets increased urinary excretion of 2.3-dinor-TXB2, as compared to the SAFA diet, whereas the urinary excretion of beta-thromboglobulin remained unchanged. As compared to the initial SAFA diet, platelet aggregation to collagen increased after both diets, while ADP induced aggregation showed no diet-induced changes. The results indicate increased platelet activity after both oil diets with no differences between the OA and LA diet and confirm in vitro findings that cis-unsaturated fatty acids have a distinct effect on cytosolic PKC, in particular.

Alpha-linolenic acid and marine long-chain n-3 fatty acids differ only slightly in their effects on hemostatic factors in healthy subjects.

The effects of alpha-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), and docosahexaenoic acid (DHA, 22:6n-3) on hemostatic factors were compared. Healthy subjects (29 women and 17 men aged 20-44 y) received either linseed oil (average ALA intake: 5.9 g/d) or fish oil plus sunflower oil (average EPA + DHA intake: 5.2 g/d) for 4 wk. The supplemented amount of fat was 1.19 mg/kJ (1 g/200 kcal) calculated energy expenditure. Stability of habitual diets was monitored. Blood samples were collected at baseline, at the end of the experimental period, and after a 12-wk follow-up period. Different changes in the study groups were seen only in serum cholesterol and triacylglycerols, platelet fatty acid composition, and ADP-induced platelet aggregation. The treatments did not differ in their effects on collagen-induced platelet aggregation and thromboxane production, aggregation to the thromboxane A2 mimic I-BOP, urinary excretion of 11-dehydro-thromboxane B2 and beta-thromboglobulin, bleeding time, plasma fibrinogen concentration, antithrombin III activity, factor VII coagulant activity, or activity of plasminogen activator inhibitor 1. The results indicate that supplemented ALA from vegetable oil and EPA and DHA from a marine source have largely parallel effects on hemostatic factors.