No game, more pain - Examining possible long term effects and underlying mechanisms of habitual violent video gaming on the acquired capability for suicide.

According to Joiner`s interpersonal-psychological theory of suicide repeated engagement in suicidal behavior or so-called painful and provocative events constitutes the acquired capability for suicide (ACS) comprising two facets: enhanced pain tolerance and fearlessness about death (FAD). Recent research showed that single bouts of violent-video-gaming (VVG) increase pain tolerance. It is unknown whether individuals who habitually play VVGs at a high frequency rate show higher signs of ACS in terms of low pain sensitivity, high tolerance and lowered FAD compared to non-gamers. In a cross-sectional case-control study, we compared pain sensitivity and tolerance during a 5-min Cold-Pressor-Test (CPT) besides FAD in young males, playing VVGs highly frequent (n = 18) vs. non-gamers (n = 17). Mood was rated before and after the CPT. We found higher CPT-pain tolerance, lower intensity ratings and higher FAD scores among gamers compared to non-gamers. A significant time x group interaction of pain ratings indicated a process of habituation in the gamers. An increase of positive mood in the gamers emphasizes the role of opponent processes. The results suggest that habitual VVG might reflect a repetitive behavior enhancing the ACS.

Climate deteriorations and Neanderthal demise in interior Iberia.

Time and circumstances for the disappearance of Neanderthals and its relationship with the advent of Modern Humans are not yet sufficiently resolved, especially in case of the Iberian Peninsula. Reconstructing palaeoenvironmental conditions during the last glacial period is crucial to clarifying whether climate deteriorations or competition and contacts with Modern Humans played the pivotal role in driving Neanderthals to extinction. A high-resolution loess record from the Upper Tagus Basin in central Spain demonstrates that the Neanderthal abandonment of inner Iberian territories 42 kyr ago coincided with the evolvement of hostile environmental conditions, while archaeological evidence testifies that this desertion took place regardless of modern humans' activities. According to stratigraphic findings and stable isotope analyses, this period corresponded to the driest environmental conditions of the last glacial apart from an even drier period linked to Heinrich Stadial 3. Our results show that during Marine Isotope Stages (MIS) 4 and 2 climate deteriorations in interior Iberia temporally coincided with northern hemisphere cold periods (Heinrich stadials). Solely during the middle MIS 3, in a period surrounding 42 kyr ago, this relation seems not straightforward, which may demonstrate the complexity of terrestrial climate conditions during glacial periods.

[Management of different cardiovascular risk factors with a combination tablet (polypill)]. / Management verschiedener kardiovaskulärer Risikofaktoren mit einem Kombinationspräparat ("Polypill").

BACKGROUND: The multifactorial origin of cardiovascular diseases has led to polypharmacy in primary and secondary prophylaxis with evidence-based medications, such as statins, antihypertensive drugs and platelet aggregation inhibitors. The number of prescribed drugs correlates inversely to adherence and can lead to treatment failure. Fixed-dose combination drugs (polypills) could increase the medication adherence of patients, reduce risks and prevent cardiovascular events. METHODS: This review is based on publications that were retrieved from Medline (via PubMed) and The Cochrane Library. The clinical database ClinicalTrials.gov. was also considered. RESULTS: In the studies on primary prevention conducted to date, fixed-dose combinations showed a superior control of risk factors, e.g. hypertension and low-density lipoprotein (LDL) cholesterol compared to placebo and at least non-inferiority compared to usual care. In secondary prevention, the effect of the polypill is mostly on the reduction of blood pressure and LDL cholesterol in non-adherent patients; however, evidence that fixed-drug combinations reduce cardiovascular morbidity and mortality compared to standard therapy is lacking. CONCLUSION: The polypill can be considered as an alternative to polypharmacy after a risk-benefit assessment, especially in non-adherent patients. Ongoing studies are investigating the effect of the polypill on cardiovascular events. Current polypills are limited by the lack of sufficient dosages of the individual components to avoid overtreatment and undertreatment at the individual treatment level.

[Clinical practice of systemic lysis in prehospital resuscitation. Success and complication rates]. / Klinische Praxis der systemischen Lyse unter prähospitaler Reanimation. Erfolgs- und Komplikationsraten.

BACKGROUND: Systemic thrombolysis was introduced as the sole prehospital treatment option in patients with cardiac arrest in the setting of acute myocardial ischemia or pulmonary embolism; however, it remains the subject of discussion. PATIENTS AND METHODS: A total of 194 patients with sudden prehospital cardiac arrest were included in this retrospective case control study. Of these patients, 96 in whom circulatory arrest due to cardiac disease (pulmonary artery embolism or myocardial ischemia) was suspected underwent thrombolytic treatment and were compared to the remaining 98 patients that did not undergo thrombolytic therapy. In addition to the circumstances of circulatory arrest, the course and success of resuscitation, as well as in-hospital course (including bleeding complications), overall survival and neurological outcomes were compared. RESULTS: There were no significant differences between patients with or without thrombolysis in terms of the circumstances of cardiac arrest. Patients that received thrombolytic treatment were significantly younger and were more frequently treated with anticoagulants, platelet aggregation inhibitors and amiodarone. They also received higher doses of epinephrine and arrived at hospital under ongoing resuscitation significantly more frequently. A trend toward more prehospital return of spontaneous circulation (ROSC) following thrombolytic treatment was seen in the entire cohort. However, patients pre-treated with acetylsalicylic acid and heparin did not show better prehospital ROSC rates as a result of additional thrombolytic therapy. Significant differences in terms of bleeding complications or the need for blood transfusion could not be seen due to the small number of patients. DISCUSSION: The indication for systemic thrombolysis in the context of prehospital resuscitation should remain restricted to patients with clear symptoms of acute pulmonary embolism or recurrent episodes of ventricular fibrillation in the setting of acute myocardial infarction. Due to a lack of evidence, systemic thrombolysis should not be used as a treatment of last resort in younger patients with persistent ventricular fibrillation.

[Change from ACE inhibitor, Ca-antagonist or beta-blocker to candesartan cilexetil: better efficacy and tolerance. SWITCH study (German study segment)]. / Wechsel von ACE-Hemmer, Ca-Antagonist oder beta-Blocker zu Candesartancilexetil: Bessere Wirksamkeit und Verträglichkeit. SWITCH-Studie (deutscher Studienteil).

BACKGROUND AND OBJECTIVE: Lack of efficacy in the treatment of hypertension with only one drug presents a problem in general practice and often requires switching to another type of drug, because higher dosage of currently used antihypertensives increases the frequency of side effects. Angiotensin II antagonists are well tolerated and there is no evidence of dose-related increase in side effects. This study in 574 hypertensives under therapy with ACE inhibitors, beta-blockers or calcium channel blockers was undertaken to determine whether direct switching to the Angiotensin II-antagonist candesartan cilexetil at its maximal dose of 16 mg is as effective and tolerable as starting therapy with candesartan cilexetil 8 mg followed by up-titration to 16 mg after 4 weeks. PATIENTS AND METHODS: 258 men (mean age 57 +/- 11 years) and 316 women (58 +/- 12) with essential hypertension (blood pressure < 180/95 mm Hg) under ambulatory therapy with ACE-inhibitors, beta-blockers or calcium channel blockers with inadequate efficacy or tolerability were switched to monotherapy with candesartan cilexetil. Half of the patients were treated with 8 mg for 4 weeks (n = 284), the other half received 16 mg (n = 290). Both groups then were treated with candesartan cilexetil, 16 mg, for further 4 weeks. Choice of treatment was doubly blinded and randomised. RESULTS: After 4 weeks significant blood pressure reduction was observed in both treatment groups (p < 0.0001 for each pretreatment group). A tendency for more adequate blood pressure reduction under initial therapy with candesartan cilexetil 16 mg was observed. There was a small further blood pressure reduction in both treatment groups after 8 weeks. In comparison with the previous medications the proportion of patients with blood pressure reduction < 90 mm Hg diastolic was doubled in both treatment arms after 4 weeks: after initial dose of candesartan cilexetil 8 mg from 36.7% to 78.8%, after initial dose of candesartan cilexetil 16 mg from 43.9% to 81.1%. Clinically relevant side effects were not observed. CONCLUSION: Switching of antihypertensive monotherapy with ACE inhibitors, beta-blockers or calcium channel blockers to candesartan cilexetil 8 mg or 16 mg under ambulatory conditions is safe and equally well tolerated and effectively reduces blood pressure.

[Vascular ergotism through inhalation of grain dust]. / Vaskulärer Ergotismus durch Getreidestaubinhalation.

HISTORY AND CLINICAL FINDINGS: For 6 months a 42-year-old farmer without cardiovascular risk factors had been suffering from increasing pain in both feet and calves. Angiography two months apart had demonstrated progressive narrowing of all lower-leg arteries. Pain-free walking had become restricted to 50 m, there were no palpable pulses in the right foot and those in the left foot were markedly reduced. INVESTIGATIONS: Occlusion pressure of the right foot was 55 mm Hg. Repeat angiography showed proximal occlusion of all three lower-leg arteries. Biopsy and biochemical tests excluded degenerative and inflammatory causes of the vascular disease. DIAGNOSIS, TREATMENT AND COURSE: Enquiry of the patient discovered that he had been exposed to ergotamine-containing milling dust in the preparation of rye flour. Inhalational intake of ergotamine was proven by a high plasma ergotamine level. Attempted treatment with prostaglandin E1 (intraarterially for 16 days), doxazosin (2 mg/d) and acetylsalicylic acid 300 mg/d) had only little effect on symptoms. But complete avoidance of exposure to flour dust slowly decreased the plasma level of ergotamine within 4 months, after which all lower-leg arteries had almost completely re-opened. CONCLUSIONS: This is the first reported case proving that chronic ergotamine inhalation can cause ergotism affecting peripheral arteries. As the plasma ergotamine level fell only slowly it must be assumed that ergotamine had accumulated in a, so far unknown, body depot with slow release into the blood.

Accuracy of the SpaceLabs Medical 90217 ambulatory blood pressure monitor.

OBJECTIVE: To test the SpaceLabs Medical 90217 ambulatory blood pressure monitor for compliance with The Association for the Advancement of Medical Instrumentation's standard and a modification of the British Hypertension Society (BHS) protocol. METHODS: The study concerned 85 subjects aged 17-88 years with various arm circumferences and ranges of blood pressure. Resting casual blood pressure was 135 +/- 24/76 +/- 14 mmHg (mean +/- SD). For each subject nine readings of the 90217 device were compared with auscultatory reference readings of two independent observers who used a dual stethoscope. The measurements were performed with subjects standing, sitting and supine. The manual reference readings were alternated with the 90217 monitor's readings. RESULTS: Average differences between manual (average of recordings by two clinicians) and automated readings were -5 +/- 4.3/0.6 +/- 4.6 mmHg (seated), 0.0 +/- 6.0/-1.8 +/- 4.7 mmHg (standing) and -1.6 +/- 5.1/-0.7 +/- 5.1 mmHg (supine).CONCLUSIONS: The device meets the Association for the Advancement of Medical Instrumentation's standard. Comparing the results with the modified BHS protocol, it was found that the device earned the highest BHS grade of 'A' both for systolic and for diastolic blood pressures.

Analysis of adverse effects among patients with essential hypertension receiving an ACE inhibitor or a beta-blocker.

Evaluation of safety and efficacy of new drugs is based largely on data from clinical trials involving a limited number of patients. This approach does not necessarily detect the rare adverse events that may only be observed when very large numbers of patients are studied. Consequently, we designed a double-blind 12-week trial comparing the new angiotensin-converting enzyme (ACE) inhibitor, quinapril (n = 5,053), with a well-established beta-adrenergic receptor blocker, metoprolol (n = 506). Essentially hypertensive patients (diastolic blood pressure 95-114 mm Hg) received either 10 mg quinapril or 50 mg metoprolol once daily, and the doses were doubled at 4-week intervals to a maximum of 40 and 200 mg, respectively, in nonresponders. Responder rates were similar under both regimens. Adverse events were assessed by interview as well as by a standard questionnaire. The overall prevalence of adverse events reported by standard questionnaire was higher than that reported spontaneously during interviews. With respect to typical ACE inhibitor adverse reactions (e.g. cough and taste disturbances), there was no difference between quinapril and metoprolol independent of the mode of reporting. In summary, both drugs showed comparable overall tolerance and safety. The discrepancy between spontaneously reported and questionnaire-reported adverse events was noteworthy, and this finding prevailed in a volunteer group of 327 patients who were treated with quinapril for 52 weeks. Thus, a questionnaire is of great significance in addition to the patient history/interview in a large-scale, double-blind study designed to learn about details of drug safety.

The ambulatory blood pressure in normotensive and hypertensive subjects: results from an international database.

OBJECTIVE: To delineate more precisely an operational threshold for making clinical decisions based on ambulatory blood pressure (ABP) measurement by studying the ABP in subjects who were diagnosed as either normotensive or hypertensive by conventional blood pressure (CBP) measurement. SUBJECTS: Twenty-four research groups recruited 7069 subjects. Of these, 4577 were normotensive (systolic CBP < or = 140 mmHg and diastolic CBP < or = 90 mmHg) and 1773 were hypertensive (systolic CBP > or = 160 mmHg and/or diastolic CBP > or = 90 mmHg). Of the latter, 1324 had systolic and 1310 had diastolic hypertension. RESULTS: Ninety-five percent of the normotensive subjects had a 24-h ABP below (systolic and diastolic, respectively) 133 and 82 mmHg. Of the patients with systolic hypertension, 24% had a 24-h systolic ABP of < 133 mmHg. Similarly, 30% of those with diastolic hypertension had a 24-h diastolic ABP of < 82 mmHg. The probability that hypertensive patients had a 24-h ABP below these thresholds was higher in women than in men, increased with age and was 2- to 4-fold greater if the CBP of the patient had been measured at only one visit and if fewer than 3 CBP measurements had been averaged to establish the diagnosis of hypertension. By contrast, for each 10-mmHg increment in systolic CBP, this probability decreased by 54% for the 24-h systolic ABP and by 25% for the 24-h diastolic ABP, and for each 5 mmHg increment in diastolic CBP it increased by 6 and 9%, respectively. CONCLUSION: The ABP distributions of the normotensive subjects included in the present international database were not materially different from those in previous reports in the literature. One-fifth to more than one-third of the hypertensive patients had an ABP which was below the 95th centile of the ABP in normotensive subjects, but this proportion decreased if the hypertensive patients had shown a higher CBP upon repeated measurement. The prognostic implications of elevated CBP in the presence of normal ABP remain to be determined.

Ambulatory blood pressure in normotensive and hypertensive subjects: results from an international database.

OBJECTIVE: To delineate more precisely an operational threshold for making clinical decisions based on ambulatory blood pressure (ABP) measurement by studying the ABP in subjects who were diagnosed as either normotensive or hypertensive by conventional blood pressure (CBP) measurement. SUBJECTS: Twenty-four research groups recruited 7069 subjects. Of these, 4577 were normotensive (CBP < or = 140/90 mmHg), 719 were borderline hypertensive (systolic CBP 141-159 mmHg or diastolic CBP 91-94 mmHg) and 1773 were definitely hypertensive. Of the subjects in the last of these categories, 1324 had systolic hypertension (systolic CBP > or = 160 mmHg) and 1310 had diastolic hypertension (diastolic CBP > or = 95 mmHg). Combined systolic and diastolic hypertension was present in 861 subjects. Hypertension had been diagnosed from the mean of two to nine (median two) CBP measurements obtained at one to three (median two) visits. RESULTS: The 95th centiles of the ABP distributions in the normotensive subjects were (systolic and diastolic, respectively) 133 and 82 mmHg for 24-h ABP, 140 and 88 mmHg for daytime ABP and 125 and 76 mmHg for night-time ABP, respectively. Of the subjects with systolic hypertension, 24% had 24-h systolic ABP < 133 mmHg. Similarly, 30% of those with diastolic hypertension had 24-h diastolic ABP < 82 mmHg. The probability that hypertensive subjects had 24-h ABP below these thresholds tended to increase with age and was two- to fourfold greater if the CBP of the subject had been measured at only one visit and if fewer than three CBP measurements had been averaged for establishing the diagnosis of hypertension. By contrast, for each 10-mmHg increment in systolic CBP, this probability decreased by 54% for 24-h systolic ABP and by 26% for 24-h diastolic ABP, and for each 5-mmHg increment in diastolic CBP it decreased by 6 and 9%, respectively. In comparison with 24-h ABP, the overlap in the daytime and night-time ABP between normotensive and hypertensive subjects was of similar magnitude and was influenced by the same factors. CONCLUSIONS: The ABP distributions of the normotensive subjects included in the present international database were not materially different from those in previous reports in the literature. One-fifth to more than one-third of hypertensive subjects had an ABP which was below the 95th centile of the ABP of normotensive subjects, but this proportion decreased if the hypertensive subjects had shown a higher CBP upon repeated measurement. The prognostic implications of elevated CBP in the presence of normal ABP remain to be determined.

Site-specific mutagenesis induced by single O6-alkylguanines (O6-n-propyl, O6-n-butyl, O6-n-octyl) in vivo.

The mutagenic activity of a series of longer chain O6-n-alkylguanine residues (O6-n-propyl, O6-n-butyl, O6-n-octyl) has been analyzed using a plasmid molecule (pUC 9) in which single O6-alkylguanines were positioned in the unique Pstl recognition site by shot gun ligation (Nucleic Acids Res. 13, 3305-3316 (1985)) of overlapping synthetic oligonucleotides. After transfection of these vectors into E. coli cells having normal DNA repair systems, progeny plasmids were produced, of which 2.6%, 2.8% and 4.3% were mutated in their Pstl site when containing O6-n-propylguanine, O6-n-butylguanine, O6-n-octylguanine, respectively. DNA sequence analysis of mutant plasmid genomes revealed that O6-n-propylguanine and O6-n-butylguanine induced exclusively G-->A transitions located specifically at the preselected site. O6-n-octylguanine induced apart from G-->A transitions (70%) also targeted G-->T transversions (30%). These results indicate that the mutation frequency of longer chain O6-alkylguanines can be substantial in cells with normal repair systems and that the mutation pattern depends on the nature of the alkyl group.

Effect of long-term hemodialysis on arterial compliance in end-stage renal failure.

To assess the influence of long-term hemodialysis on arterial compliance, the elastic vessel wall properties of the common carotid artery were determined in 20 normotensive renal transplant recipients (age 44.7 +/- 4.1 years) 8-12 weeks after first transplantation and in 10 healthy controls (age 45.9 +/- 5.2 years). Arterial distension was measured by using a multigate pulsed Doppler system, blood pressure curve was recorded by finger-plethysmography. 10 patients with a prior long-term hemodialysis of 51 +/- 11 months were compared to 10 patients with a prior short hemodialysis of 18 +/- 7 months. The patients and controls had been matched in respect of age, sex and blood pressure. In the long and short-term hemodialysis group, the proportion of patients (n = 10) with a history of mild hypertension was similar--mild hypertension for 25 +/- 10 months (n = 5) and for 27 +/- 9 months (n = 5). In the group with long-term hemodialysis, the cross-sectional compliance and the distensibility coefficient was significantly reduced in comparison to the group with short-term hemodialysis (p < 0.005) and to the control group (p < 0.001). A significant inverse correlation between the hemodialysis period and the distensibility coefficient (r = -0.59; p < 0.005) showed a decrease in arterial compliance with the length of hemodialysis treatment. The results demonstrate that vessel wall elasticity decreases with the length of hemodialysis treatment and is reduced by hemodialysis-dependent factors, which are detached from sustained arterial hypertension. As cause of reduced arterial compliance in long-term hemodialysis hypervolemia, hypercirculation and disturbed calcium-phosphate metabolism is suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

Torasemide in comparison with thiazides in the treatment of hypertension.

There are a number of clinically relevant differences between torasemide and the thiazide diuretics in the treatment of hypertension. Only 2.5-5 mg torasemide once daily is sufficient for antihypertensive treatment; these low doses of torasemide exert comparable antihypertensive effects to those of the overtly natriuretic doses of thiazides (e.g., hydrochlorothiazide 25 mg) that are currently used once daily for the treatment of hypertension. Whereas natriuretic thiazide doses reduce blood pressure rapidly, the blood pressure-lowering effect of low-dose torasemide appears to occur more gradually during the first weeks of treatment. The diurnal blood pressure rhythm is not altered by either drug. In contrast to the thiazides, torasemide does not cause significant renal potassium loss in doses recommended to treat hypertension. Long-term antihypertensive treatment with torasemide has not resulted in undesired metabolic side effects, such as hypomagnesemia, alterations in glucose and lipid metabolism, or hyperuricemia. As compared with the thiazides, torasemide appears to be a safer and equally effective alternative for antihypertensive treatment when subdiuretic doses of this loop diuretic are used.

[Cortical necrosis of the transplanted kidney. MR tomographic confirmation of the diagnosis?]. / Die Rindennekrose der Transplantatniere. MR-tomographische Sicherung der Diagnose?

Cortical necrosis is a rare complication of renal transplants, which requires urgent diagnosis and management to avoid unnecessary immunosuppression. Seven renal transplants with suspected cortical necrosis were evaluated by Doppler-US, 99mTc-DTPA-perfusion study and Gd-DTPA-enhanced dynamic MRI. In four transplants, cortical necrosis was confirmed by angiography and histology. In diagnosing cortical necrosis with preserved medullary perfusion (n = 2) dynamic MRI was superior to the other modalities. Totally necrotic renal transplants (n = 2) were reliably diagnosed by all imaging methods.

[Adrenal cortex carcinoma: diagnosis, therapy and course in 10 cases]. / Das Nebennierenrindenkarzinom: Diagnostik, Therapie und Verlauf in zehn Fällen.

Data from ten cases with carcinoma of the adrenal cortex, diagnosed between 1981 and 1988, have been extensively reevaluated. Six patients suffered from a hormonally active tumor with proven clinical and laboratory signs of hypercortisolism and/or hyperandrogenism. Female patients dominated the cohort (eight of ten). No preference for particular age (35 to 64, mean 52) or lateralisation of the tumor was recognisable. In all cases signs for endocrinopathy and/or tumor disease lead to investigative intervention. Nonspecific symptoms like pain, reduction of weight and fatigue were registered most frequently. In three patients an abdominal tumor was palpable. Investigation of hormone levels and imaging procedures (sonography and CT scan) assured correct diagnosis in all cases. Since prior to operation metastases have been detected in five cases and in eight cases capsular invasion was proven histologically only, one patient was free of tumor after operation but developed hepatic metastases later on. Altogether nine of ten patients developed metastases later on. Seven of the patients died from the perioperative period up to 8.4 +/- 8.15 months. Mean survival of all patients was 20.5 +/- 24.5 months. Histological grading and assessment of anaplasia did not correlate with either survival or tumor stage. None of the patients presented with tumor stage I according to the TNM system by MacFarlane (55). All four patients with advanced disease in stage IV died within the first year after operation. Eight patients were treated with 1 to 6 g of the adrenolytic o,p'DDD (mitotane, Lysodren). In one of these cases, a sonographically documented remission lasting for over eight years was observed. A second patient with anaplastic carcinoma showed a reduction of the size of pulmonary metastases under continuous therapy with o,p'DDD and a cyclic polychemotherapy. After the latter was discontinued, the course was progressive.

[Evaluation parameters of ambulatory blood pressure monitoring: mean values versus percent values]. / Auswerteparameter der ABDM: Mittelwerte versus Prozentwerte.

In 1039 ambulatory blood pressure (BP) recordings, we studied if mean values or blood-pressure load (% of elevated readings) is superior for evaluation. There was a nonlinear correlation between the two parameters with high correlation coefficients (syst. r = 0.98, diast. r = 0.97). At very high (low) BP levels the differentiation of the percentage-scale is insufficient, whereas in the central BP range it is too detailed as compared with the accuracy and reproducibility. Due to the nonlinear correlation with BP, treatment effects cannot be easily compared by percentage-values, since identical BP differences correspond with varying percentage. Intervals between readings are usually shorter during daytime than during nighttime. In contrast to the BP load, the resulting problems for 24-h statistics can be easily avoided by calculation of weighted mean values (from hourly means). In summary, weighted mean values are rather suited for evaluation of ambulatory blood pressure than is BP load.