Peri-operative management of patients with type-2 diabetes mellitus undergoing non-cardiac surgery using liraglutide, glucose-insulin-potassium infusion or intravenous insulin bolus regimens: a randomised controlled trial.

In this open-label multicentre randomised controlled trial, we investigated three peri-operative treatment strategies to lower glucose and reduce the need for rescue insulin in patients aged 18-75 years with type-2 diabetes mellitus undergoing non-cardiac surgery. Patients were randomly allocated using a web-based randomisation program to premedication with liraglutide (liraglutide group), glucose-insulin-potassium infusion (insulin infusion group) or insulin bolus regimen (insulin bolus group), targeting a glucose < 8.0 mmol.l-1 . The primary outcome was the between group difference in median glucose levels 1 h after surgery. We analysed 150 patients (liraglutide group n = 44, insulin infusion group n = 53, insulin bolus group n = 53) according to the intention-to-treat principle. Median (IQR [range]) plasma glucose 1 h postoperatively was lower in the liraglutide group compared with the insulin infusion and insulin bolus groups (6.6 (5.6-7.7 [4.2-13.5]) mmol.l-1 vs. 7.5 (6.4-8.3 [3.9-16.6]) mmol.l-1 (p = 0.026) and 7.6 (6.4-8.9 [4.7-13.2]) mmol.l-1 ) p = 0.006, respectively). The incidence of hypoglycaemia and postoperative complications did not differ between the groups. Six patients had pre-operative nausea in the liraglutide group, of which two had severe nausea, compared with no patients in the insulin infusion and insulin bolus groups (p = 0.007). The pre-operative administration of liraglutide stabilised peri-operative plasma glucose levels and reduced peri-operative insulin requirements, at the expense of increased pre-operative nausea rates.

Surgical management of chest injuries in patients with multiple and/or severe trauma- a systematic review and clinical practice guideline update.

PURPOSE: Our aim was to update evidence-based and consensus-based recommendations for the surgical and interventional management of blunt or penetrating injuries to the chest in patients with multiple and/or severe injuries on the basis of current evidence. This guideline topic is part of the 2022 update of the German Guideline on the Treatment of Patients with Multiple and/or Severe Injuries. METHODS: MEDLINE and Embase were systematically searched to May and June 2021 respectively for the update and new questions. Further literature reports were obtained from clinical experts. Randomised controlled trials, prospective cohort studies, cross-sectional studies and comparative registry studies were included if they compared interventions for the surgical management of injuries to the chest in patients with multiple and/or severe injuries. We considered patient-relevant clinical outcomes such as mortality, length of stay, and diagnostic test accuracy. Risk of bias was assessed using NICE 2012 checklists. The evidence was synthesised narratively, and expert consensus was used to develop recommendations and determine their strength. RESULTS: One study was identified. This study compared wedge resection, lobectomy and pneumonectomy in the management of patients with severe chest trauma that required some form of lung resection. Based on the updated evidence and expert consensus, one recommendation was modified and two additional good practice points were developed. All achieved strong consensus. The recommendation on the amount of blood loss that is used as an indication for surgical intervention in patients with chest injuries was modified to reflect new findings in trauma care and patient stabilisation. The new good clinical practice points (GPPs) on the use of video-assisted thoracoscopic surgery (VATS) in patients with initial circulatory stability are also in line with current practice in patient care. CONCLUSION: As has been shown in recent decades, the treatment of chest trauma has become less and less invasive for the patient as diagnostic and technical possibilities have expanded. Examples include interventional stenting of aortic injuries, video-assisted thoracoscopy and parenchyma-sparing treatment of lung injuries. These less invasive treatment concepts reduce morbidity and mortality in the primary surgical phase following a chest trauma.

Quality of recovery after day care surgery with app-controlled remote monitoring: study protocol for a randomized controlled trial.

BACKGROUND: The majority of surgical interventions are performed in day care and patients are discharged after the first critical postoperative period. At home, patients have limited options to contact healthcare providers in the hospital in case of severe pain and nausea. A smartphone application for patients to self-record pain and nausea when at home after day care surgery might improve patient's recovery. Currently patient experiences with smartphone applications are promising; however, we do not know whether remote monitoring with such an application also improves the patient's recovery. This study aims to evaluate the experienced quality of recovery after day care surgery between patients provided with the smartphone application for remote monitoring and patients receiving standard care without remote monitoring. METHODS: This non-blinded randomized controlled trial with mixed methods design will include 310 adult patients scheduled for day care surgery. The intervention group receives the smartphone application with text message function for remote monitoring that enables patients to record pain and nausea. An anaesthesia professional trained in empathetic communication, who will contact the patient in case of severe pain or nausea, performs daily monitoring. The control group receives standard care, with post-discharge verbal and paper instructions. The main study endpoint is the difference in perceived quality of recovery, measured with the QoR-15 questionnaire on the 7th day after day care surgery. Secondary endpoints are the overall score on the Quality of Recovery-15 at day 1, 4 and 7-post discharge, the perceived quality of hospital aftercare and experienced psychological effects of remote monitoring during postoperative recovery from day care surgery. DISCUSSION: This study will investigate if facilitating patients and healthcare professionals with a tool for accessible and empathetic communication might lead to an improved quality of the postoperative recovery period. TRIAL REGISTRATION: The 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial' is approved and registered on 23 February 2022 by Research Ethics Committees United with registration number R21.076/NL78144.100.21. The protocol NL78144.100.21, 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial', is registered at the ClinicalTrials.gov public website (registration date 16 February 2022; NCT05244772).

Distinct cytokine and regulatory T cell profile at pleural sites of dual HIV/tuberculosis infection compared to that in the systemic circulation.

Pleural tuberculosis (TB) remains a common presentation of Mycobacterium tuberculosis (MTB) infection in HIV/TB dually infected subjects, and both cellular and acellular components of the pleural milieu promote HIV-1 replication; however, they remain uncharacterized. Using cytokine array of pleural fluid and real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunophenotype analysis, pleural fluid mononuclear cells (PFMC) were compared to systemic counterparts [i.e. plasma and peripheral blood mononuclear cells (PBMC)]. Significant increases in pleural fluid cytokines compared to plasma were limited to interleukin (IL)-6, IL-8, interferon (IFN)-γ and transforming growth factor (TGF)-ß, and did not include other T helper type 1 (Th1) (IL-2, IL-15), Th2 or Th17 cytokines. Patterns and levels of cytokines were indistinguishable between pleural fluid from HIV/TB and TB patients. Forkhead box P3 (FoxP3) mRNA in PFMC was increased significantly and correlated highly with levels of IL-6 and IL-8, less with TGF-ß, and not with IFN-γ. Among CD4 T cells, FoxP3-reactive CD25(hi) were increased in HIV/TB dually infected subjects compared to their PBMC, and up to 15% of FoxP3(+) CD25(hi) CD4 T cells were positive for IL-8 by intracellular staining. These data implicate a dominant effect of MTB infection (compared to HIV-1) at pleural sites of dual HIV/TB infection on the local infectious milieu, that include IL-6, IL-8, IFN-γ and TGF-ß and regulatory T cells (T(reg) ). A correlation in expansion of T(reg) with proinflammatory cytokines (IL-6 and IL-8) in pleural fluid was shown. T(reg) themselves may promote the inflammatory cytokine milieu through IL-8.

Genetic regulation of commitment to interleukin 4 production by a CD4(+) T cell-intrinsic mechanism.

The dysregulated expression of interleukin 4 (IL-4) can have deleterious effects on the outcome of infectious and allergic diseases. Despite this, the mechanisms by which naive T cells commit to IL-4 expression during differentiation into mature effector cells remain incompletely defined. As compared to cells from most strains of mice, activated CD4(+) T cells from BALB mice show a bias towards IL-4 production and T helper 2 commitment in vitro and in vivo. Here, we show that this bias arises not from an increase in the amount of IL-4 produced per cell, but rather from an increase in the proportion of CD4(+) T cells that commit to IL-4 expression. This strain-specific difference in commitment was independent of signals mediated via the IL-4 receptor and hence occurred upstream of potential autoregulatory effects of IL-4. Segregation analysis of the phenotype in an experimental backcross cohort implicated a polymorphic locus on chromosome 16. Consistent with a role in differentiation, expression of the phenotype was CD4(+) T cell intrinsic and was evident as early as 16 h after the activation of naive T cells. Probabilistic gene activation is proposed as a T cell-intrinsic mechanism capable of modulating the proportion of naive T cells that commit to IL-4 production.

[Vaginal prolapse and rectal obstruction. Treated with a vaginal vault mesh colpo suspension and laparoscopic resection rectopexy]. / Vaginalprolaps und Defäkationsobstruktion. Kombination einer Netzkolposuspension mit der laparoskopischen Resektionsrektopexie.

BACKGROUND: Stool outlet obstruction with incomplete or complete rectal prolapse combined with vaginal vault prolapse is a severe form of pelvic floor insufficiency. Combining laparoscopic resection rectopexy with a vaginal vault mesh colpo suspension is a possible way of correcting this defect. METHOD: The safety of the combination was evaluated in 18 patients. RESULTS: The procedure was performed successfully with no complications in 16 of the 18 patients. One patient suffered intraoperative rectal injury and therefore received no polypropylene mesh, and one showed intraoperative bleeding requiring transfusion. No secondary surgery was required. Hospital stay lasted an average of 11.4 days (range 8-20) and the urinary catheters could be removed after an average of 4.3 days (range 2-10). No urinary disturbances were noted at the time of hospital release. Short-term mild fever appeared in 28% of cases (5/18). There were two urinary tract infections. No disturbance in healing and no anastomotic insufficiency were observed. The duration of postoperative antibiotic therapy averaged 3 days (range 0-8). CONCLUSION: The combination of laparoscopic resection rectopexy with a vaginal vault mesh colpo suspension might be safe. The close contact between the mesh and anastomosis might induce no increase in insufficiency. Long-term outcome must still be evaluated.

Sputum smear-positive, culture-negative state during anti-tuberculosis treatment in the MGIT liquid culture era.

The sputum smear-positive, culture-negative state poses a challenge for clinicians. Previous studies have shown that most samples with positive smears during the later stages of treatment are culture-negative. Earlier studies generally used solid culture media, which tend to be less sensitive than current liquid culture systems. We examined the smear-positive, culture-negative state in the era of MGIT™ 960™ liquid cultures. We found that the smear-positive, culture-negative state occurred less frequently with MGIT culture, and that the majority of the samples with late positive smears were culture-negative, regardless of media type.

Reader variability and validation of the Timika X-ray score during treatment of pulmonary tuberculosis.

SETTING: Chest radiographs (CXRs) are widely used for diagnosing pulmonary TB and assessing response to therapy. The Timika X-ray score has been proposed as a tool for measuring disease severity and predicting treatment outcome. OBJECTIVE: To evaluate inter- and intra-reader agreement of Timika scores and assess the ability of the score to predict microbiologic outcome at 2 months. DESIGN: Analytical validation study. Disease severity was measured by two readers using pretreatment radiographs and follow-up films taken at 2, 6 and 12 months after the start of treatment among 110 human immunodeficiency virus negative adults with pulmonary TB. One fourth of the films were reread to assess intra-reader agreement. RESULTS: The two-component Timika score had high inter- and intra-reader agreement (intraclass correlation (ICC)inter = 75%, ICCintra > 0.81). Baseline Timika score was associated with positive month 2 smear (P = 0.0004) and culture status (P = 0.03). The average Timika score declined significantly over the course of successful treatment. CONCLUSION: The Timika score showed good inter- and intra-reader agreement and a significant association with microbiological outcomes after 2 months of treatment. The results of this study strengthen the evidence supporting the use of the Timika score for measuring disease severity on CXR.

Defective Connective Tissue Remodeling in Smad3 Mice Leads to Accelerated Aneurysmal Growth Through Disturbed Downstream TGF-ß Signaling.

Aneurysm-osteoarthritis syndrome characterized by unpredictable aortic aneurysm formation, is caused by SMAD3 mutations. SMAD3 is part of the SMAD2/3/4 transcription factor, essential for TGF-ß-activated transcription. Although TGF-ß-related gene mutations result in aneurysms, the underlying mechanism is unknown. Here, we examined aneurysm formation and progression in Smad3-/- animals. Smad3-/- animals developed aortic aneurysms rapidly, resulting in premature death. Aortic wall immunohistochemistry showed no increase in extracellular matrix and collagen accumulation, nor loss of vascular smooth muscle cells (VSMCs) but instead revealed medial elastin disruption and adventitial inflammation. Remarkably, matrix metalloproteases (MMPs) were not activated in VSMCs, but rather specifically in inflammatory areas. Although Smad3-/- aortas showed increased nuclear pSmad2 and pErk, indicating TGF-ß receptor activation, downstream TGF-ß-activated target genes were not upregulated. Increased pSmad2 and pErk staining in pre-aneurysmal Smad3-/- aortas implied that aortic damage and TGF-ß receptor-activated signaling precede aortic inflammation. Finally, impaired downstream TGF-ß activated transcription resulted in increased Smad3-/- VSMC proliferation. Smad3 deficiency leads to imbalanced activation of downstream genes, no activation of MMPs in VSMCs, and immune responses resulting in rapid aortic wall dilatation and rupture. Our findings uncover new possibilities for treatment of SMAD3 patients; instead of targeting TGF-ß signaling, immune suppression may be more beneficial.

Impact of experimentally induced serotonin deficiency by tryptophan depletion on sleep EEG in healthy subjects.

The tryptophan depletion test is a research strategy to investigate the functional consequences of decreasing the brain serotonin metabolism. Because serotonin is involved in sleep regulation and the regulation of affective states, we studied the acute polysomnographic effects of tryptophan depletion and expected to induce similar changes of sleep EEG as observed in depressed patients. A total of 12 healthy subjects (mean age 34 +/- 3 years) had eight polysomnograms, divided in two blocks of 4 consecutive nights. After one adaptation and 1 baseline night, subjects received a low-protein diet on day 3 and 4 until midday. On day 4 at 18.00 h, they drank an amino acid mixture either devoid of tryptophan or containing 2.3 g of tryptophan (placebo control) in randomized and double-blind order, resulting in an 85% decrease (tryptophan depletion) and a 144% increase (placebo control) of serum tryptophan at 22.00 h. After tryptophan depletion but not placebo, significant effects on sleep EEG were observed in terms of decreased non-rapid eye movement (non-REM) stage 2, increase of wake %, and of rapid eye movement (REM) density compared with baseline. REM latency was not altered, however the first and second REM period interval were significantly shorter after tryptophan depletion. This study underlines the impact of the serotonergic system on sleep maintenance and on REM sleep.

Absence of a significant linkage between Na(+),K(+)-ATPase subunit (ATP1A3 and ATP1B3) genotypes and bipolar affective disorder in the old-order Amish.

Previous studies provide evidence for a genetic component for susceptibility to bipolar affective disorder (BPAD) in the old-order Amish population. El-Mallakh and Wyatt [1995: Biol Psychiatry 37:235-244] have suggested that the Na(+),K(+)-ATPase may be a candidate gene for BPAD. This study examines the relationship between BPAD in the old-order Amish cohort and the Na(+),K(+)-ATPase alpha1 and beta3 subunit genes (ATP1A3, ATP1B3). A total of 166 sibling pairs were analyzed for linkage via nonparametric methods. Suggestive levels of statistical significance were not reached in any stratification model for affective illness. Overall, the results do not support linkage of bipolar disorder to the Na(+),K(+)-ATPase alpha subunit gene (ATP1A3) and beta subunit gene (ATP1B3) in these old-order Amish families and they show that these Na(+),K(+)-ATPase subunit genes are not major effect genes (>or=fourfold increased genetic risk of disease) for BPAD in the old-order Amish pedigrees. We cannot exclude other genetic variants of the Na(+),K(+)-ATPase hypothesis for BPAD, whereby other loci may modifying Na(+),K(+)-ATPase activity.

Lack of association between a biallelic polymorphism in the adducin gene and blood pressure in whites and African Americans.

Population-based candidate gene association analyses are becoming increasingly popular as a result of a greater number of genes and gene polymorphisms having been identified for which some functional information is available. Because many biochemical and physiologic systems impact blood pressure regulation and hypertension susceptibility, many of these identified genes and polymorphisms are candidates for population-level association studies involving blood pressure levels or hypertension status. Recent studies have suggested that the alpha-adducin gene may harbor polymorphisms that influence blood pressure level. Therefore, we embarked on a study to test one such polymorphism in two large US samples: one from an urban African American population (Maywood, IL) and another from a rural white population (Tecumseh, MI). We used both family-based association tests and tests that consider the impact of additional measured factors beyond adducin gene variation on blood pressure levels. We found no evidence for a significant effect of the chosen adducin polymorphism on blood pressure variation in either sample. We also found no association between Adducin genotypes and antihypertensive use. These facts, together with similar findings in companion studies, suggest that the alpha-adducin gene polymorphism does not have a pronounced effect on blood pressure variation in the populations studied. This does not suggest, however, that the alpha-adducin gene does not have a role in blood pressure regulation and hypertension susceptibility.

Programmed ventricular stimulation in survivors of acute myocardial infarction: long-term follow-up.

The prognostic significance of ventricular tachyarrhythmias induced by programmed ventricular stimulation was evaluated in 492 consecutive survivors of acute myocardial infarction (AMI). Holter monitoring, signal-averaged electrocardiogram (ECG) and measurement of left ventricular ejection fraction (EF) were also performed. The protocol used up to 3 extrastimuli. Sustained monomorphic ventricular tachycardia (VT) < 270 beats/min, > 270 beats/min (ventricular flutter) (VFI), and ventricular fibrillation (VF) were induced in 99, 66 and 52 patients, respectively. Long term follow-up (mean 3.7 +/- 2.2 years) showed that most episodes of VT occurred during the first months following AMI (n = 14), but some patients (n = 6) could develop VT as late as 4 years after AMI. Sudden death (SD) (n = 22) always occurred during the first year following AMI. Multivariate analysis demonstrated that EF < 30% and induction of a VT < 270 beats/min were the only predictors for total cardiac death (P < 0.001). EF < 30%, induction of a VT < 270 beats/min and also of VFI (P < 0.05) were predictors for VT and SD: the risk was 4% in patients without inducible VT, 12% in those with inducible VF1, and 21% in those with inducible VT < 270 beats/min. In conclusion, induction of a sustained monomorphic VT < 270 beats/min or > 270 beats/min is a predictor of arrhythmic events during the first year as well as 4 years after myocardial infarction. However the risk of arrhythmic sudden death decreases after the first year, while the risk of VT persists. Because of the low positive predictive value of programmed stimulation (respectively 21% and 12% for the induction of a sustained VT and VFI), we recommended the indication of programmed stimulation in only the patients with one abnormal non-invasive investigation.

Significance and prevalence of inducible atrial tachyarrhythmias in patients undergoing electrophysiologic study for presyncope or syncope.

The purpose of the study was to report the prevalence of inducible supraventricular tachyarrhythmias (SVTA) in 827 consecutive patients aged 17 to 90 years who did not have spontaneous documented SVTA and who had unexplained presyncope and/or syncope. The electrophysiologic study (EPS) included programmed atrial and ventricular stimulation up to two extrastimuli at three cycle lengths, and the study of sino-atrial and AV conduction. The results were as follows. EPS was normal in 386 patients. Inducible junctional tachycardia or atrial flutter and fibrillation was the only finding in 187 patients (23%). In the remaining patients we found ventricular tachycardia in 103 (12%), heart block in 67 (8%), sick sinus syndrome in 56 (7%) and increased vagal tone in 28 (3%). The presence of an underlying heart disease (47%) and salvos of atrial premature beats on Holter monitoring (39%) were significantly correlated with the induction of SVTA. However, the comparison with similar groups without syncope indicates that only the induction of SVTA in patients with hypertrophic cardiomyopathy and mitral valve prolapse was significantly correlated with the history of syncope. In patients without heart disease or with prior myocardial infarction or decreased left ventricular function, the induction of SVTA, which is not associated with hypotension in the supine position, could require an induction after head-up tilting, because of the lack of specificity of programmed stimulation in these patients. Programmed atrial stimulation should be systematically performed in patients with unexplained syncope, in particular in those with hypertropic cardiomyopathy and mitral valve prolapse, who require a specific treatment, if a SVTA is induced. In other patients the results of programmed atrial stimulation should be interpreted cautiously.

Mixture distributions in human genetics research.

The use of mixture distributions in genetics research dates back to at least the late 1800s when Karl Pearson applied them in an analysis of crab morphometry. Pearson's use of normal mixture distributions to model the mixing of different species of crab (or 'families' of crab as he referred to them) within a defined geographic area motivated further use of mixture distributions in genetics research settings, and ultimately led to their development and recognition as intuitive modelling devices for the effects of underlying genes on quantitative phenotypic (i.e. trait) expression. In addition, mixture distributions are now used routinely to model or accommodate the genetic heterogeneity thought to underlie many human diseases. Specific applications of mixture distribution models in contemporary human genetics research are, in fact, too numerous to count. Despite this long, consistent and arguably illustrious history of use, little mention of mixture distributions in genetics research is made in many recent reviews on mixture models. This review attempts to rectify this by providing insight into the role that mixture distributions play in contemporary human genetics research. Tables providing examples from the literature that describe applications of mixture models in human genetics research are offered as a way of acquainting the interested reader with relevant studies. In addition, some of the more problematic aspects of the use of mixture models in genetics research are outlined and addressed.

Interpretation of secondary electron images obtained using a low vacuum SEM.

Charging of insulators in a variable pressure environment was investigated in the context of secondary electron (SE) image formation. Sample charging and ionized gas molecules present in a low vacuum specimen chamber can give rise to SE image contrast. "Charge-induced" SE contrast reflects lateral variations in the charge state of a sample caused by electron irradiation during and prior to image acquisition. This contrast corresponds to SE emission current alterations produced by sub-surface charge deposited by the electron beam. "Ion-induced" contrast results from spatial inhomogeneities in the extent of SE signal inhibition caused by ions in the gaseous environment of a low vacuum scanning electron microscope (SEM). The inhomogeneities are caused by ion focusing onto regions of a sample that correspond to local minima in the magnitude of the surface potential (generated by sub-surface trapped charge), or topographic asperities. The two types of contrast exhibit characteristic dependencies on microscope operating parameters such as scan speed, beam current, gas pressure, detector bias and working distance. These dependencies, explained in terms of the behavior of the gaseous environment and sample charging, can serve as a basis for a correct interpretation of SE images obtained using a low vacuum SEM.

Spider (Araneus diadematus) cocoon silk: a case of non-periodic lattice crystals with a twist?

Transmission electron microscopy was used to investigate the supramolecular structure of Araneus diadematus (garden spider) cocoon silk. Electron diffraction patterns contain features which are consistent with the presence of non-periodic lattice crystals, i.e. highly frustrated crystalline regions as identified previously in the major ampullate silk (MAS, dragline) of Nephila clavipes spiders. The diffraction patterns further suggest that crystals in A. diadematus cocoon silk may be twisted parallel to the chain direction, offering a potential explanation for the lower tensile stiffness of this fibre relative to MAS.

Dynamic secondary electron contrast effects in liquid systems studied by environmental scanning electron microscopy.

We report an investigation into a dynamic contrast phenomenon in water-oil emulsions imaged in the environmental scanning electron microscope. Secondary electron contrast between oil and water phases is shown to change with scan rate, even inverting in extreme cases. This effect is attributed to the fact that charge carriers in liquids have intermediate mobilities compared with those in metallic conductors and solid insulators. Thus, increasing the electron energy flux density (via slower scan rates) results in the temporary accumulation of excess charge, which in turn gives rise to increased secondary electron emission. Excess charge dissipates between frames, however, such that classical charging of the specimen is not observed. The oils used here have conductivities lower than that of water, making them more susceptible to the effect. However, the material within the primary electron interaction volume is a conductive medium. We demonstrate that charging effects are not seen in regions of the oil where the interaction volume is in contact with the more conductive continuous water phase. Secondary electron emission from these regions therefore approximates to the intrinsic yield.

[Results of the systematic application of ventricular stimulation methods]. / Résultats de l'application systématique des méthodes de stimulation ventriculaire.

This study was undertaken to test the validity of methods of evaluating ventricular tachycardia and in therapeutic surveillance. One hundred and thirty nine patients aged 16 to 84 years, with and without severe ventricular arrhythmias (ventricular tachycardia, VT, and fibrillation, VF) were divided into two groups after clinical, echocardiographic and 24 hour Holter investigations: Group I comprised 26 patients with a least one documented attack of VT or VF; Group II comprised 113 patients without these arrhythmias, who complained of dizziness, syncope, and/or their ECG showed a conduction defect, and so electrophysiological investigation was undertaken. A protocol of ventricular stimulation was undertaken in addition to the usual measurements of conduction times, comprising incremental ventricular stimulation from 100 to 200/min, single and paired extrastimulus in sinus rhythm and during ventricular pacing at rates of 100 and 150/min, the first extrastimulus being programmed 10 ms after the end of the ventricular effective refractory period. Excluding bundle to bundle reentry, the following results were obtained: In Group I: VT was triggered 16 times (61,5 p. 100), and in 4 of these cases VF occurred and required defibrillation. Ten patients had previous myocardial infarction; 5 patients had left ventricular dilatation. In 2 cases runs of 3 or 4 VES were recorded. No arrhythmia could be induced in 8 cases (30,8 p. 100); 5 of these patients had apparently normal hearts. In Group II: VT (greater than 5 VES) was triggered in 22 cases (19,5 p. 100) and in 4 cases this degenerated to VF requiring defibrillation. 11 patients had apparently normal hearts; 6 patients had left ventricular dilatation and 4 patients had previous myocardial infarction. 1 to 4 repetitive VES were observed in 67 cases (59,3 p. 100): the heart was judged to be normal in all patients except those with previous infarction. No correlation was established between the ability to induce VT and age, syncope, or ECG changes (especially bundle branch block). However, a correlation was found between the induction of VT and underlying cardiac disease and the method of induction of VT; in Group II, all episodes of VT were triggered by delivering paired ventricular extrastimuli on a background paced rhythm. These results show that repetitive ventricular responses can easily be triggered and that this has no pathological significance.(ABSTRACT TRUNCATED AT 400 WORDS)