Peptidyl-Prolyl-cis/trans-Isomerases Mip and PpiB of Legionella pneumophila Contribute to Surface Translocation, Growth at Suboptimal Temperature, and Infection.

The gammaproteobacterium Legionella pneumophila is the causative agent of Legionnaires' disease, an atypical pneumonia that manifests itself with severe lung damage. L. pneumophila, a common inhabitant of freshwater environments, replicates in free-living amoebae and persists in biofilms in natural and man-made water systems. Its environmental versatility is reflected in its ability to survive and grow within a broad temperature range as well as its capability to colonize and infect a wide range of hosts, including protozoa and humans. Peptidyl-prolyl-cis/trans-isomerases (PPIases) are multifunctional proteins that are mainly involved in protein folding and secretion in bacteria. In L. pneumophila the surface-associated PPIase Mip was shown to facilitate the establishment of the intracellular infection cycle in its early stages. The cytoplasmic PpiB was shown to promote cold tolerance. Here, we set out to analyze the interrelationship of these two relevant PPIases in the context of environmental fitness and infection. We demonstrate that the PPIases Mip and PpiB are important for surfactant-dependent sliding motility and adaptation to suboptimal temperatures, features that contribute to the environmental fitness of L. pneumophila Furthermore, they contribute to infection of the natural host Acanthamoeba castellanii as well as human macrophages and human explanted lung tissue. These effects were additive in the case of sliding motility or synergistic in the case of temperature tolerance and infection, as assessed by the behavior of the double mutant. Accordingly, we propose that Mip and PpiB are virulence modulators of L. pneumophila with compensatory action and pleiotropic effects.

Auditory hallucinations in adults with hearing impairment: a large prevalence study.

BACKGROUND: Similar to visual hallucinations in visually impaired patients, auditory hallucinations are often suggested to occur in adults with hearing impairment. However, research on this association is limited. This observational, cross-sectional study tested whether auditory hallucinations are associated with hearing impairment, by assessing their prevalence in an adult population with various degrees of objectified hearing impairment. METHODS: Hallucination presence was determined in 1007 subjects aged 18-92, who were referred for audiometric testing to the Department of ENT-Audiology, University Medical Center Utrecht, the Netherlands. The presence and severity of hearing impairment were calculated using mean air conduction thresholds from the most recent pure tone audiometry. RESULTS: Out of 829 participants with hearing impairment, 16.2% (n = 134) had experienced auditory hallucinations in the past 4 weeks; significantly more than the non-impaired group [5.8%; n = 10/173; p < 0.001, odds ratio 3.2 (95% confidence interval 1.6-6.2)]. Prevalence of auditory hallucinations significantly increased with categorized severity of impairment, with rates up to 24% in the most profoundly impaired group (p < 0.001). The corrected odds of hallucination presence increased 1.02 times for each dB of impairment in the best ear. Auditory hallucinations mostly consisted of voices (51%), music (36%), and doorbells or telephones (24%). CONCLUSIONS: Our findings reveal that auditory hallucinations are common among patients with hearing impairment, and increase with impairment severity. Although more research on potential confounding factors is necessary, clinicians should be aware of this phenomenon, by inquiring after hallucinations in hearing-impaired patients and, conversely, assessing hearing impairment in patients with auditory hallucinations, since it may be a treatable factor.

Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

High educational performance is a distinctive feature of bipolar disorder: a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls.

BACKGROUND: Schizophrenia is associated with lower intelligence and poor educational performance relative to the general population. This is, to a lesser degree, also found in first-degree relatives of schizophrenia patients. It is unclear whether bipolar disorder I (BD-I) patients and their relatives have similar lower intellectual and educational performance as that observed in schizophrenia. METHOD: This cross-sectional study investigated intelligence and educational performance in two outpatient samples [494 BD-I patients, 952 schizophrenia spectrum (SCZ) patients], 2231 relatives of BD-I and SCZ patients, 1104 healthy controls and 100 control siblings. Mixed-effects and regression models were used to compare groups on intelligence and educational performance. RESULTS: BD-I patients were more likely to have completed the highest level of education (odds ratio 1.88, 95% confidence interval 1.66-2.70) despite having a lower IQ compared to controls (ß = -9.09, S.E. = 1.27, p < 0.001). In contrast, SCZ patients showed both a lower IQ (ß = -15.31, S.E. = 0.86, p < 0.001) and lower educational levels compared to controls. Siblings of both patient groups had significantly lower IQ than control siblings, but did not differ on educational performance. IQ scores did not differ between BD-I parents and SCZ parents, but BD-I parents had completed higher educational levels. CONCLUSIONS: Although BD-I patients had a lower IQ than controls, they were more likely to have completed the highest level of education. This contrasts with SCZ patients, who showed both intellectual and educational deficits compared to healthy controls. Since relatives of BD-I patients did not demonstrate superior educational performance, our data suggest that high educational performance may be a distinctive feature of bipolar disorder patients.

First successful reduction of clinical allergenicity of food by genetic modification: Mal d 1-silenced apples cause fewer allergy symptoms than the wild-type cultivar.

BACKGROUND: Genetic modification of allergenic foods such as apple has the potential to reduce their clinical allergenicity, but this has never been studied by oral challenges in allergic individuals. METHODS: We performed oral food challenges in 21 apple-allergic individuals with Elstar apples which had undergone gene silencing of the major allergen of apple, Mal d 1, by RNA interference. Downregulation of Mal d 1 gene expression in the apples was verified by qRT-PCR. Clinical responses to the genetically modified apples were compared to those seen with the wild-type Elstar using a visual analogue scale (VAS). RESULTS: Gene silencing produced two genetically modified apple lines expressing Mal d 1.02 and other Mal d 1 gene mRNA levels which were extensively downregulated, that is only 0.1-16.4% (e-DR1) and 0.2-9.9% (e-DR2) of those of the wild-type Elstar, respectively. Challenges with these downregulated apple lines produced significantly less intense maximal symptoms to the first dose (Vmax1) than with Elstar (Vmax1 Elstar 3.0 mm vs 0.0 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 0.043), as well as significantly less intense mean symptoms per dose (meanV/d) than with Elstar (meanV/d Elstar 2.2 mm vs 0.2 mm for e-DR1, P = 0.017 and 0.0 mm for e-DR2, P = 0.043). Only one subject (5%) remained symptom-free when challenged with the Elstar apple, whereas 43% did so with e-DR1 and 63% with e-DR2. CONCLUSION: These data show that mRNA silencing of Mal d 1 results in a marked reduction of Mal d 1 gene expression in the fruit and reduction of symptoms when these apples are ingested by allergic subjects. Approximately half of the subjects developed no symptoms whatsoever, and virtually all subjects wished to consume the apple again in the future.

Genetic and environmental influences on cortical surface area and cortical thickness in bipolar disorder.

BACKGROUND: The risk of developing bipolar disorder (BD) has been linked to structural brain abnormalities. The degree to which genes and environment influence the association of BD with cortical surface area remains to be elucidated. In this twin study, genetic and environmental contributions to the association between liability to develop BD and surface area, thickness and volume of the cortex were examined. METHOD: The study cohort included 44 affected monozygotic (nine concordant, 12 discordant) and dizygotic (four concordant, 19 discordant) twin pairs, and seven twins from incomplete discordant monozygotic and dizygotic discordant twin pairs. In addition, 37 monozygotic and 24 dizygotic healthy control twin pairs, and six twins from incomplete monozygotic and dizygotic control pairs were included. RESULTS: Genetic liability to develop BD was associated with a larger cortical surface in limbic and parietal regions, and a thicker cortex in central and parietal regions. Environmental factors related to BD were associated with larger medial frontal, parietal and limbic, and smaller orbitofrontal surfaces. Furthermore, thinner frontal, limbic and occipital cortex, and larger frontal and parietal, and smaller orbitofrontal volumes were also associated with environmental factors related to BD. CONCLUSIONS: Our results suggest that unique environmental factors play a prominent role in driving the associations between liability to develop BD and cortical measures, particularly those involving cortical thickness. Further evaluation of their influence on the surface and thickness of the cortical mantle is recommended. In addition, cortical volume appeared to be primarily dependent on surface and not thickness.

Genetic influences on thinning of the cerebral cortex during development.

During development from childhood to adulthood the human brain undergoes considerable thinning of the cerebral cortex. Whether developmental cortical thinning is influenced by genes and if independent genetic factors influence different parts of the cortex is not known. Magnetic resonance brain imaging was done in twins at age 9 (N = 190) and again at age 12 (N = 125; 113 repeated measures) to assess genetic influences on changes in cortical thinning. We find considerable thinning of the cortex between over this three year interval (on average 0.05 mm; 1.5%), particularly in the frontal poles, and orbitofrontal, paracentral, and occipital cortices. Cortical thinning was highly heritable at age 9 and age 12, and the degree of genetic influence differed for the various areas of the brain. One genetic factor affected left inferior frontal (Broca's area), and left parietal (Wernicke's area) thinning; a second factor influenced left anterior paracentral (sensory-motor) thinning. Two factors influenced cortical thinning in the frontal poles: one of decreasing influence over time, and another independent genetic factor emerging at age 12 in left and right frontal poles. Thus, thinning of the cerebral cortex is heritable in children between the ages 9 and 12. Furthermore, different genetic factors are responsible for variation in cortical thickness at ages 9 and 12, with independent genetic factors acting on cortical thickness across time and between various brain areas during childhood brain development.

Publisher Correction: Associations between subjective well-being and subcortical brain volumes.

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Associations between subjective well-being and subcortical brain volumes.

To study the underpinnings of individual differences in subjective well-being (SWB), we tested for associations of SWB with subcortical brain volumes in a dataset of 724 twins and siblings. For significant SWB-brain associations we probed for causal pathways using Mendelian Randomization (MR) and estimated genetic and environmental contributions from twin modeling. Another independent measure of genetic correlation was obtained from linkage disequilibrium (LD) score regression on published genome-wide association summary statistics. Our results indicated associations of SWB with hippocampal volumes but not with volumes of the basal ganglia, thalamus, amygdala, or nucleus accumbens. The SWB-hippocampus relations were nonlinear and characterized by lower SWB in subjects with relatively smaller hippocampal volumes compared to subjects with medium and higher hippocampal volumes. MR provided no evidence for an SWB to hippocampal volume or hippocampal volume to SWB pathway. This was in line with twin modeling and LD-score regression results which indicated non-significant genetic correlations. We conclude that low SWB is associated with smaller hippocampal volume, but that genes are not very important in this relationship. Instead other etiological factors, such as exposure to stress and stress hormones, may exert detrimental effects on SWB and the hippocampus to bring about the observed association.

[A man with a classic serious milk-alkali syndrome and a carcinoma of the stomach]. / Een man met een ernstig klassiek melk-alkalisyndroom en een maagcarcinoom.

A 42-year-old man was transferred to the Emergency Department after his friends had found him unresponsive and confused in his room. He had been experiencing upper abdominal complaints for a period of several months. He had taken large amounts of a calcium carbonate/magnesium subcarbonate preparation (Rennie) and had consumed at least 3 litres of dairy products per day. His behaviour was reported as being more and more abnormal during the previous few weeks. On admission he was confused and agitated and had involuntary movements of his limbs. Laboratory investigation indicated a triple acid base disorder, i.e. metabolic alkalosis, respiratory alkalosis and high anion gap metabolic acidosis, with severe dehydration. The metabolic alkalosis was caused by the intake of large amounts of dairy and antacids: milk-alkali syndrome. The metabolic acidosis was the result of hypovolaemia and pre-renal renal failure and the respiratory alkalosis was caused by hyperventilation due to the organic psychosyndrome. The patient was treated with volume expansion by isotonic saline and the administration of potassium and he was sedated with low-dose midazolam, which led to a full respiratory compensation of the metabolic alkalosis. A few days following admission, both the plasma calcium concentration and renal function returned to normal; the acid-base disorder completely normalized and the organic psychosyndrome disappeared. On gastroduodenoscopy a gastric ulcer was found; biopsies revealed a signet ring cell adenocarcinoma of the stomach.

A study of genetic and environmental contributions to structural brain changes over time in twins concordant and discordant for bipolar disorder.

This is the first longitudinal twin study examining genetic and environmental contributions to the association between liability to bipolar disorder (BD) and changes over time in global brain volumes, and global and regional measures of cortical surface area, cortical thickness and cortical volume. A total of 50 twins from pairs discordant or concordant for BD (monozygotic: 8 discordant and 3 concordant pairs, and 1 patient and 3 co-twins from incomplete pairs; dizygotic: 6 discordant and 2 concordant pairs, and 1 patient and 7 co-twins from incomplete pairs) underwent magnetic resonance imaging twice. In addition, 57 twins from healthy twin pairs (15 monozygotic and 10 dizygotic pairs, and 4 monozygotic and 3 dizygotic subjects from incomplete pairs) were also scanned twice. Mean follow-up duration for all twins was 7.5 years (standard deviation: 1.5 years). Data were analyzed using structural equation modeling software OpenMx. The liability to BD was not associated with global or regional structural brain changes over time. Although we observed a subtle increase in cerebral white matter in BD patients, this effect disappeared after correction for multiple comparisons. Heritability of brain changes over time was generally low to moderate. Structural brain changes appear to follow similar trajectories in BD patients and healthy controls. Existing brain abnormalities in BD do not appear to progressively change over time, but this requires additional confirmation. Further study with large cohorts is recommended to assess genetic and environmental influences on structural brain abnormalities in BD, while taking into account the influence of lithium on the brain.

The EuroSCORE as predictor for prolonged hospital and intensive care stay after cardiac surgery?

OBJECTIVE: Validation of the EuroSCORE as predictor for a prolonged hospital and intensive care stay after CABG vs. institution-specific scoring systems. METHODS: For the evaluation of a prolonged hospital stay, 3359 patients were included in the analysis of EuroSCORE vs. the CORRAD morbidity score. For a prolonged intensive care stay, 1638 patients were included in the analysis of the EuroSCORE vs. the PICUS score. RESULTS: There was no significant difference in hospital stay between the three different EuroSCORE risk groups. The difference in hospital stay between the high-risk and low-risk groups, identified by the CORRAD morbidity score, was significant (6.9 vs.11.2 days). For a prolonged intensive care stay, the patients identified as high risk by the EuroSCORE and by the PICUS score also had a significantly longer intensive care stay; however, the discriminatory power was low. CONCLUSION: The EuroSCORE is not of value as a predictive system for a prolonged hospital stay. There is a relation between the high-risk patients identified by the EuroSCORE and a prolonged intensive care stay.

A new model for diurnal blood pressure profiling. Square wave fit compared with conventional methods.

For the characterization of diurnal blood pressure variation, we developed a simple mathematical model that nevertheless does justice to the specific form characteristics of individual blood pressure registrations. Analysis was based on 24-hour continuous intra-arterial measurement of blood pressure obtained in 23 hospitalized patients with mild-to-moderate untreated essential hypertension (mean +/- SD, 112 +/- 13 mm Hg). The day-night difference for mean arterial pressure varied markedly (mean, 18.6 mm Hg; range, 6.8-36.0). Inspection of profiles suggested a model of blood pressure as two contiguous, complementary periods of constant pressure, a so-called square wave. Determination of the times of transience between both periods (segmentation) was performed individually using a least-square error criterion. Results were compared with those obtained by conventional methods, including analysis by Fourier modeling. The square wave fit accounted for a larger fraction (66%) of circadian variance of mean arterial pressure than modeling based on segmentation by visual inspection (59%, considerable observer bias) or by clock time (50%). Application of the Minnesota Cosinor Method resulted in the poorest description (47%). Segmentation based on harmonic modeling (61%) appeared to be cumbersome (10 harmonics needed), and the significance of additional information offered over the square wave fit is dubious. Observer bias makes segmentation by visual inspection unsuitable for assessment of the circadian variance of blood pressure. Even when daily activities are strictly regulated (hospital environment), circadian variance is not well modeled by clock time. As compared with harmonic analysis, square wave fitting is simple, and it appears to best model the circadian variance. The method can also be applied to data obtained from noninvasive ambulatory blood pressure monitoring.

Prevention of cytomegalovirus-related death by passive immunization. A double-blind placebo-controlled study in kidney transplant recipients treated for rejection.

In a double-blind placebo-controlled study, the value of prophylactic anti-CMV immunoglobulin administration was evaluated in 39 kidney transplant recipients treated for rejection with rabbit antithymocyte globulin. Passive immunization completely prevented CMV-related death, although it did not reduce the incidence of CMV isolation, viremia, or disease. The effect of passive immunization was exclusively observed in CMV-seronegative recipients of a CMV-seropositive kidney donor. It could be demonstrated even when instituted when antirejection therapy was started. Seropositive recipients did not benefit from immunoglobulin treatment. Moreover, CMV-seronegative recipients of a kidney from a seronegative donor were not at risk for CMV infection at all. Therefore passive immunization should be restricted to seronegative recipients of seropositive allograft donors treated for rejection.

Influence of age on survival, late hypertension, and recoarctation in elective aortic coarctation repair. Including long-term results after elective aortic coarctation repair with a follow-up from 25 to 44 years.

The optimal age for elective repair of aortic coarctation is controversial. The optimal age should be associated with a minimal risk of recoarctation, late hypertension, and other cardiovascular disorders. The purpose of this retrospective study is to determine the actuarial survival after aortic coarctation repair 25 years or more after operation and to calculate the optimal age for elective aortic coarctation repair. From 1948 to 1966, 120 consecutive patients underwent aortic coarctation repair. Eighty-seven were male (72.5%). The mean age at operation was 15.5 years (SD +/- 9.1 years). Resection and end-to-end anastomosis was performed in 103 patients (85.8%). Early mortality occurred in 6 patients as a result of surgical problems, whereas late mortality in 15 patients was predominantly caused by cardiac causes. The mean follow-up period was 32 years (range 25 to 44.2 years). Ninety-two patients 96.8%) were in New York Heart Association class I. The probability of survival 44 years after operation was 73%. Patients younger than 10 years at operation had the highest probability of survival at 97%. Multivariate analysis produced age at operation as the only incremental risk factor for the occurrence of recoarctation, of late hypertension, and of premature death. So that these sequelae can be avoided, elective aortic coarctation repair should be performed around 1.5 years of age. At that age, the probability of recoarctation will have decreased to less than 3%, and the probability of upper body normotension and long-term survival will be optimal.

Decision making for the surgical management of aortic coarctation associated with ventricular septal defect.

Coarctation of the aorta and associated ventricular septal defect may be repaired simultaneously or by initial coarctation repair with or without banding of the pulmonary artery. The question is whether specific preoperative criteria can enable the surgeon to choose the optimal surgical management. Between 1980 and 1993, 80 infants younger than 3 months with coarctation and ventricular septal defect were treated surgically. In 64 infants (multistage group), simple coarctation repair was performed through a posterolateral approach, with concomitant banding of the pulmonary artery in 10 infants. Twenty ventricular septal defects were closed as a secondary procedure and four were closed as a tertiary procedure. Sixteen infants (single-stage group) underwent one-stage repair through an anterior midline approach. The total in-hospital mortality rate was 7.5%. Freedom from recoarctation after 5 years was 91.3% in the multistage group versus 60.0% in the single-stage group (p = 0.018). Freedom from secondary ventricular septal defect treatment in the multistage group after 5 years was 40.7%, versus 100% in the single-stage group (p = 0.016). Thirty-seven ventricular septal defects (47.8%) closed spontaneously. In particular, the preoperative left-to-right shunt and extension of the perimembranous VSD into the inlet or outlet were risk factors for the need for eventual surgical ventricular septal defect closure after initial coarctation repair. On the basis of these two risk factors, the probability of the need for eventual surgical treatment of ventricular septal defect after initial coarctation repair can be calculated. This policy offers a well-considered choice between single-stage and multistage repair, weighing the risk of secondary ventricular septal defect treatment versus the risk of recoarctation. Finally, the number of surgical procedures per infant will be as low as possible.

Third-time coronary artery bypass grafting.

BACKGROUND: In this study we analyze the short- and long-term results, and the clinical, functional, and subjective status of patients after a second coronary reoperation (RE-RE-CABG). METHODS: The perioperative data of 33 consecutive patients undergoing RE-RE-CABG (1987 to 1998) were studied. Follow-up information was obtained from our follow-up databank. A cross-sectional follow-up was conducted, with additional functional evaluation by the Duke Activity Status Index (DASI), and patients' evaluations of their life situation were registered. RESULTS: Perioperative mortality was 2 of 33 patients (6%). During the follow-up (mean 51.6 months) 5 patients died. The 26 survivors showed a significant decrease in New York Heart Association class from 3.6+/-0.4 preoperatively versus 2.2+/-0.6 postoperatively. The mean Duke Activity Status Index score was 29.30+/-16.34 (range 7.22 to 48.9). In all, 18 of 26 patients (70%) were declared to have benefitted from the RE-RECABG. CONCLUSIONS: The significant improve in New York Heart Association class and good postoperative functional capacity, justified the RE-RE-CABG. However, patients must be informed about the limitations of this procedure.

Sternal wound complications after primary isolated myocardial revascularization: the importance of the post-operative variables.

OBJECTIVE: Select pre-, peri-, and post-operative variables, predictive for sternal wound complications (SWC), in a clinical setting. METHODS: We analyzed pre-, peri-, and post-operative data of 3815 patients who underwent a primary isolated bypass grafting. 100 patients (2.6%) had post-operative SWC. Unifactor and multifactor risk analysis, were used for statistical analysis. RESULTS: Unifactor analysis identified age (P=0.05), obesity (P=0.001), lung disease (P=0.001), extracorporeal circulation >100 min (P=0.02), graft choice (P=0.01), post-operative low cardiac output, reoperation, nephrological, pulmonary problems (P<0.001) as risk factors. Multifactor analysis, identified obesity (P=0.005), reoperation (P=0.01), nephrological (P=0.0001), pulmonary problems (P=0.001) and No-IMA-use (P=0.05) as independent predictors. Age <50 years (P=0.04) decreased the risk for SWC. There is, however, an interaction of the graft-use and the pre-operative and post-operative predictors, that can mask the precise effect of the graft-use. CONCLUSION: Reoperation, nephrological and pulmonary problems are strong predictors, obesity and age independent preoperative risk factors for sternal wound complications.

Mechanism of action of ketanserin in hypertension and vasospastic disease.

It remains to be established whether ketanserin's antihypertensive effect is caused by blockade of serotonergic type 2 receptors (S2), by blockade of alpha 1-adrenoceptors or by combined effect on both receptors. We therefore performed several clinical studies. Ketanserin, 10 mg i.v., lowered blood pressure in 6 patients with essential hypertension and blocked, at the same time, the contraction of hand veins to exogenous serotonin. In contrast, ketanserin had no effect on the venoconstrictor action of noradrenaline. Ketanserin also did not alter the pressor effect of bolus injections of the alpha 1-agonist phenylephrine. Furthermore, ketanserin had a distinct hypotensive effect in 4 normotensive patients with autonomic insufficiency who were unresponsive to alpha 1-adrenoceptor blockade. Moreover, the ketanserin-induced marked increase in digital blood flow in 7 patients with Raynaud's phenomenon was not blocked by pretreatment with high doses of the alpha 1-adrenoceptor blockade. However, in patients with essential hypertension, the antihypertensive effect of ketanserin was blunted by pretreatment with prazosin. This may be related to S2 blockade of the alleged amplifying effect of serotonin on alpha 1-adrenoceptor mediated vasoconstriction but the data do not exclude concomitant alpha-blockade by ketanserin. We conclude that the mechanism of ketanserin's antihypertensive effect requires further clarification; nevertheless the data cited above do not support the view that ketanserin is nothing more than another alpha-blocker.

[Life threatening hyperkalemia: the value of the electrocardiogram]. / Levensbedreigende hyperkaliëmie: de waarde van het elektrocardiogram.

In two men, aged 19 and 64, with chronic renal insufficiency and subacute symptoms of malaise and weakness of the leg muscles, broad QRS complexes were seen in the ECG. The younger patient developed an asystole and resuscitation was unsuccessful. His blood potassium level was found to be 8.3 mmol/l. The older patient recovered after administration of calcium gluconate. His blood potassium level was found to be 8.5 mmol/l. An 80-year-old woman who was taking various drugs because of heart failure also complained of muscle weakness. Her blood potassium level was 7.2 mmol/l and her ECG showed narrow complexes. She recovered without calcium gluconate after a change in medication. Hyperkalemia is a potentially life-threatening electrolyte disorder that may require immediate treatment. The changes in the ECG, especially widening of the QRS complexes, are the most important clues to the severity of the hyperkalemia. A treatment protocol based on ECG changes may reduce the mortality in these patients.