[Intoxicated women: A study into gender differences in substance abuse in forensic psychiatric patients]. / Vrouwen onder invloed: een studie naar genderverschillen in middelengebruik bij forensisch psychiatrische patiënten.

BACKGROUND: Substance abuse is an important risk factor for (violent) offending, but is mostly studied in male populations. More knowledge about women is needed.
AIM: To gain insight into possible gender differences in substance abuse and offending in forensic psychiatric patients.
METHOD: Files were analysed of 275 women and 275 men who have been admitted between 1984 and 2014 to one of four Dutch forensic psychiatric facilities and related to incidents of violence during treatment or recidivism after discharge (for 78 women).
RESULTS: Although substance abuse was common in women (57%), it was significantly more prevalent in men (68%). Men were more often diagnosed with substance dependency and more often committed the index-offense whilst intoxicated. Predictive accuracy for violent incidents during treatment was better for men. Both women and men with substance abuse had significantly more historical risk factors compared to those without substance abuse. A history of substance abuse was not a significant predictor for recidivism after discharge in women.
CONCLUSION: There are gender differences in substance abuse and the relationship with offending was stronger for men. These differences may have implications for substance use treatment in forensic mental health services.

Cerebral autoregulatory performance and the cerebrovascular response to head-of-bed positioning in acute ischaemic stroke.

BACKGROUND AND PURPOSE: Cerebrovascular responses to head-of-bed positioning in patients with acute ischaemic stroke are heterogeneous, questioning the applicability of general recommendations on head positioning. Cerebral autoregulation is impaired to various extents after acute stroke, although it is unknown whether this affects cerebral perfusion during posture change. We aimed to elucidate whether the cerebrovascular response to head position manipulation depends on autoregulatory performance in patients with ischaemic stroke. METHODS: The responses of bilateral transcranial Doppler ultrasound-determined cerebral blood flow velocity (CBFV) and local cerebral blood volume (CBV), assessed by near-infrared spectroscopy of total hemoglobin tissue concentration ([total Hb]), to head-of-bed lowering from 30° to 0° were determined in 39 patients with acute ischaemic stroke and 17 reference subjects from two centers. Cerebrovascular autoregulatory performance was expressed as the phase difference of the arterial pressure-to-CBFV transfer function. RESULTS: Following head-of-bed lowering, CBV increased in the reference subjects only ([total Hb]: + 2.1 ± 2.0 vs. + 0.4 ± 2.6 µM; P < 0.05), whereas CBFV did not change in either group. CBV increased upon head-of-bed lowering in the hemispheres of patients with autoregulatory performance <50th percentile compared with a decrease in the hemispheres of patients with better autoregulatory performance ([total Hb]: +1.0 ± 1.3 vs. -0.5 ± 1.0 µM; P < 0.05). The CBV response was inversely related to autoregulatory performance (r = -0.68; P < 0.001) in the patients, whereas no such relation was observed for CBFV. CONCLUSION: This study is the first to provide evidence that cerebral autoregulatory performance in patients with acute ischaemic stroke affects the cerebrovascular response to changes in the position of the head.

European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology.

BACKGROUND AND PURPOSE: Current guidelines on cerebral venous thrombosis (CVT) diagnosis and management were issued by the European Federation of Neurological Societies in 2010. We aimed to update the previous European Federation of Neurological Societies guidelines using a clearer and evidence-based methodology. METHOD: We followed the Grading of Recommendations, Assessment, Development and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews and writing recommendations based on the quality of available scientific evidence. RESULTS: We suggest using magnetic resonance or computed tomographic angiography for confirming the diagnosis of CVT and not routinely screening patients with CVT for thrombophilia or cancer. We recommend parenteral anticoagulation in acute CVT and decompressive surgery to prevent death due to brain herniation. We suggest preferentially using low-molecular-weight heparin in the acute phase and not direct oral anticoagulants. We suggest not using steroids and acetazolamide to reduce death or dependency. We suggest using antiepileptics in patients with an early seizure and supratentorial lesions to prevent further early seizures. We could not make recommendations concerning duration of anticoagulation after the acute phase, thrombolysis and/or thrombectomy, therapeutic lumbar puncture, and prevention of remote seizures with antiepileptic drugs. We suggest that, in women who have suffered a previous CVT, contraceptives containing oestrogens should be avoided. We suggest that subsequent pregnancies are safe, but use of prophylactic low-molecular-weight heparin should be considered throughout pregnancy and puerperium. CONCLUSIONS: Multicentre observational and experimental studies are needed to increase the level of evidence supporting recommendations on the diagnosis and management of CVT.

Shunting in acute cerebral venous thrombosis: a systematic review.

BACKGROUND AND PURPOSE: The efficacy of cerebrospinal fluid shunting to reduce intracranial hypertension and prevent fatal brain herniation in acute cerebral venous thrombosis (CVT) is unknown. METHOD: From the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) and a systematic literature review, we retrieved acute CVT patients treated only with shunting (external ventricular drain, ventriculoperitoneal or ventriculojugular shunt). Outcome was classified at 6 months and final follow-up by the modified Rankin Scale (mRS). RESULTS: 15 patients were collected (9 from the ISCVT and 6 from the review) who were treated with a shunt (external ventricular drain in 6 patients, a ventriculoperitoneal shunt in 8 patients or an unspecified type of shunt in another one). Eight patients (53.3%) regained independence (mRS 0-2), while 2 patients (13.3%) were left with a severe handicap (mRS 4-6) and 4 (26.7%) died despite treatment. Five patients with parenchymal lesions were shunted within 48 h from admission deterioration, 4 with an external ventricular drain: 2 (40%) recovered to independence, 2 (40%) had a severe handicap and 1 (20%) died. In contrast, all 3 patients with intracranial hypertension and no parenchymal lesions receiving a ventriculoperitoneal shunt later than 48 h regained independence. CONCLUSION AND IMPLICATIONS: A quarter of acute CVT patients treated with a shunt died, and only half regained independence. With the limitation of the small number of subjects, this review suggests that shunting does not appear to be effective in preventing death from brain herniation in acute CVT. We cannot exclude that shunting may benefit patients with sustained intracranial hypertension and no parenchymal lesions.

[Violent women: a multicentre study of the characteristics of female forensic psychiatric patients]. / Gewelddadige vrouwen: een multi-centeronderzoek naar kenmerken van vrouwelijke forensisch psychiatrische patiënten.

BACKGROUND: Violence perpetrated by women has attracted more and more attention in the past few years. However, there is lack of background information about women admitted to forensic psychiatric hospitals and about risk factors for recidivism. AIM: To conduct a multicenter study which will give more insight into female psychiatric patients and which will probably have implications for psychodiagnostics, risk assessment and treatment in (forensic) psychiatric settings. METHOD: We coded the files of 297 women who, between 1984 and 2013, had been admitted to one of four Dutch forensic psychiatric facilities by reason of violent delinquent behaviour. We used an extensive coding list and several risk assessment tools including the recently developed Female Additional Manual (fam) for women. RESULTS: The general picture that emerged was one of severely traumatised women with complex pathology and a high level of comorbidity. Many of the women had experienced previous treatment failures and had caused many incidents during treatment. CONCLUSION: Female forensic psychiatric patients are a complex group that deserves more specific attention. Attention for traumas from the past, intensive supervision in relationships and training for staff in dealing with, for instance, manipulative behaviour are the most important implications from this study.

Safety of lumbar puncture in patients with cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Lumbar puncture (LP) may precipitate cerebral venous thrombosis (CVT), but it is unclear if LP is deleterious in patients with CVT. We aimed to assess the safety of LP in the International Study on Cerebral Veins and Dural Sinus Thrombosis prospective cohort. METHODS: In 624 patients with CVT, we compared the prognosis of patients submitted or not to LP. The primary outcome was 'death or dependency at 6 months', as evaluated by the modified Rankin Scale (mRS; mRS = 3-6, with adjustment for variables associated with poor prognosis); secondary outcomes were: 'worsening after admission'; 'acute death'; and 'complete recovery at 6 months' (mRS = 0-1). We analyzed the same outcomes in subgroups of patients with brain lesions on the admission computer tomography/magnetic resonance imaging. RESULTS: LP was performed in 224 patients (35.9%). There was no difference in frequency of 'death or dependency at 6 months' between patients with or without LP [13.4% vs. 14.4%; odds ratio (OR) = 0.9, 95% confidence interval (CI) 0.6-1.5; P = 0.739]. LP was not associated with 'worsening after hospitalization' [21.5% vs. 23.5%; OR = 0.9, 95% CI 0.6-1.3; P = 0.577], 'acute death' [3.6% vs. 3.3%; OR = 1.1, 95% CI 0.5-2.7; P = 0.844] or 'complete recovery' [79.9% vs. 76.6%; OR = 1.2, 95% CI 0.8-1.7; P = 0.484]. In the subgroups of patients with brain lesions, the prognoses were not different between patients submitted or not to LP. CONCLUSION: LP was not associated with the functional outcome of patients with CVT, suggesting that LP was not harmful in these patients. These results should not be generalized to patients with large brain lesions and risk of herniation where LP is contraindicated.

Long-term satisfaction after neurological second opinions and tertiary referrals.

BACKGROUND AND PURPOSE: The number of second opinions (SO) and tertiary referrals (TR) in neurology is increasing. Previously, we showed that a day-care admission for neurological SO's and TR's often results in a new diagnosis and/or treatment advice and increases patient satisfaction. However, long-term satisfaction for these consultations has never been studied. The main purpose of this study was to investigate long-term satisfaction in these groups of patients. METHODS: A 2-year follow-up study in 300 patients who had attended a day-care clinic for SO and TR. Long-term satisfaction was assessed with a questionnaire using four Visual Analogue Scale (VAS) satisfaction items (ranging 0-10). Patients were asked if they had sought further consultations for the same problem after they had consulted the day-care clinic. A model was constructed to assess predictors for seeking new consultations. RESULTS: Overall satisfaction decreased 2.4 (SD 2.4) points during follow-up to the same level as before the consultation. The decrease was similar in SO and TR patients. Twenty-eight per cent of the patients consulted other health-care workers. Greater satisfaction immediately after the consultation was the only predictor for not seeking additional consultations (OR 0.78, 95% CI 0.61-0.99 for every point increase on VAS). CONCLUSION: Despite a high rate of new diagnoses and advised treatments, long-term satisfaction decreased after 2 years to baseline levels. These results question the long-term efficacy of a day-care clinic to evaluate neurological second opinions and tertiary referrals.

Increased sodium intake and decreased sodium excretion in ICU-acquired hypernatremia: A prospective cohort study.

PURPOSE: To provide more in-depth insight in the development of early ICU-acquired hypernatremia in critically ill patients based on detailed, longitudinal and quantitative data. MATERIALS AND METHODS: A comparative analysis was performed using prospectively collected data of ICU patients. All patients requiring ICU admission for more than 48 h between April and December 2018 were included. For this study, urine samples were collected daily and analyzed for electrolytes and osmolality. Additionally, plasma osmolality analyses were performed. Further data collection consisted of routine laboratory results, detailed fluid balances and medication use. RESULTS: A total of 183 patient were included for analysis, of whom 38% developed ICU-acquired hypernatremia. Whereas the hypernatremic group was similar to the non-hypernatremic group at baseline and during the first days, hypernatremic patients had a significantly higher sodium intake on day 2 to 5, a lower urine sodium concentration on day 3 and 4 and a worse kidney function (plasma creatinine 251 versus 71.9 µmol/L on day 5). Additionally, hypernatremic patients had higher APACHE IV scores (67 versus 49, p < 0.05) and higher ICU (23 versus 12%, p = 0.07) and 90-day mortality (33 versus 14%, p < 0.01). CONCLUSIONS: Longitudinal analysis shows that the development of early ICU-acquired hypernatremia is preceded by increased sodium intake, decreased renal function and decreased sodium excretion.

EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients.

BACKGROUND: Cerebral venous and sinus thrombosis (CVST) is a rather rare disease which accounts for <1% of all strokes. Diagnosis is still frequently overlooked or delayed as a result of the wide spectrum of clinical symptoms and the often subacute or lingering onset. Current therapeutic measures which are used in clinical practice include the use of anticoagulants such as dose-adjusted intravenous heparin or body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH), the use of thrombolysis and symptomatic therapy including control of seizures and elevated intracranial pressure. METHODS: We searched MEDLINE (National Library of Medicine), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Library to review the strength of evidence to support these interventions and the preparation of recommendations on the therapy of CVST based on the best available evidence. Review articles and book chapters were also included. Recommendations were reached by consensus. Where there was a lack of evidence but consensus was clear we stated our opinion as good practice points. RESULTS AND CONCLUSIONS: Patients with CVST without contraindications for anticoagulation (AC) should be treated either with body weight-adjusted subcutaneous LMWH or with dose-adjusted intravenous heparin (level B recommendation). Concomitant intracranial haemorrhage (ICH) related to CVST is not a contraindication for heparin therapy. The optimal duration of oral anticoagulant therapy after the acute phase is unclear. Oral AC may be given for 3 months if CVST was secondary to a transient risk factor, for 6-12 months in patients with idiopathic CVST and in those with "mild" thrombophilia, such as heterozygous factor V Leiden or prothrombin G20210A mutation and high plasma levels of factor VIII. Indefinite AC should be considered in patients with recurrent episodes of CVST and in those with one episode of CVST and 'severe' thrombophilia, such as antithrombin, protein C or protein S deficiency, homozygous factor V Leiden or prothrombin G20210A mutation, antiphospholipid antibodies and combined abnormalities (good practice point). There is insufficient evidence to support the use of either systemic or local thrombolysis in patients with CVST. If patients deteriorate despite adequate AC and other causes of deterioration have been ruled out, thrombolysis may be a therapeutic option in selected cases, possibly in those without large ICH and threatening herniation (good practice point). There are no controlled data about the risks and benefits of certain therapeutic measures to reduce an elevated intracranial pressure (with brain displacement) in patients with severe CVST. However, in severe cases with impending herniation craniectomy can be used as a life-saving intervention (good practice point).

Antiplatelet therapy in combination with rt-PA thrombolysis in ischemic stroke (ARTIS): rationale and design of a randomized controlled trial.

BACKGROUND: Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is currently the only approved acute therapy for ischemic stroke. After rt-PA-induced recanalization, reocclusion is observed in 20-34%, probably caused by platelet activation. In acute myocardial infarction, the combination of thrombolytic and antiplatelet therapy leads to a better outcome compared to thrombolytic treatment alone. In patients with acute ischemic stroke, several studies showed that those on antiplatelet treatment prior to rt-PA had an equal or even better outcome compared to patients without prior use of antiplatelet therapy, despite an increased risk of bleeding. METHODS: We present the protocol of a multicenter randomized clinical trial (n = 800) investigating the effects of immediate addition of aspirin to rt-PA on poor outcome (modified Rankin score >2) in ischemic stroke patients. CONCLUSION: This study will answer the question whether the combination of rt-PA and antiplatelet therapy improves the functional outcome in ischemic stroke patients.

Regulated membrane localization of Tiam1, mediated by the NH2-terminal pleckstrin homology domain, is required for Rac-dependent membrane ruffling and C-Jun NH2-terminal kinase activation.

Rho-like GTPases, including Cdc42, Rac, and Rho, regulate signaling pathways that control actin cytoskeletal structures and transcriptional activation. The Tiam1 gene encodes an activator of Rac1, and similarly to constitutively activated (V12)Rac1, overexpression of Tiam1 in fibroblasts induces the formation of membrane ruffles. Tiam1 contains a Dbl homology (DH) domain and adjacent pleckstrin homology (PH) domain, hallmarks for activators of Rho-like GTPases. Unique for Tiam1 are an additional PH domain and a Discs-large homology region in the NH2-terminal part of the protein. Here we show that both in fibroblasts and COS cells, membrane localization of Tiam1 is required for the induction of membrane ruffling. A detailed mutational analysis, in combination with confocal laser scanning microscopy and immunoelectron microscopy, demonstrates that the NH2-terminal PH domain of Tiam1, but not the DH-adjacent PH domain, is essential for membrane association. This NH2-terminal PH domain of Tiam1 can be functionally replaced by the myristoylated membrane localization domain of c-Src, indicating that the primary function of this PH domain is to localize the protein at the membrane. After serum starvation, both membrane association of Tiam1 and ruffling can be induced by serum, suggesting that receptor stimulation induces membrane translocation of Tiam1. Similar to V12Rac1, Tiam1 stimulates the activity of the c-Jun NH2-terminal kinase (JNK). This Rac-dependent stimulation of JNK also requires membrane association of Tiam1. We conclude that the regulated membrane localization of Tiam1 through its NH2-terminal PH domain determines the activation of distinct Rac-mediated signaling pathways.

Second opinions and tertiary referrals in neurology: a prospective observational study.

BACKGROUND AND OBJECTIVE: The number of neurological second opinions (SO) and tertiary referrals (TR) is increasing. The main purpose of this study was to assess whether a day-care admission made a meaningful contribution to standard neurological outpatient care, for a wide range of second opinions and tertiary referrals. METHODS: All new patients attending an academic neurological day-care clinic in a 6-month period were investigated. Before admission, all previous medical correspondence and ancillary investigations were reviewed. On the day of admission, extensive time was available for clinical evaluation and additional ancillary investigations and an attempt was made to come to a final diagnosis. Demographic characteristics, duration of symptoms, patient satisfaction, new diagnoses and treatment consequences were studied. RESULTS: 300 patients (183 SO and 117 TR) were evaluated. In total 103 patients (35 %) received a new diagnosis (26 % SO vs. 48 % TR, p < 0.001) and 69 (67 %) of these had therapeutic implications. A new treatment advice was given to a total of 149 patients (50 %), which was similar in both groups (48 % vs. 53 %). Second opinions were considered medically less relevant than tertiary referrals (39 % vs. 64 %, p < 0.001). The number of new diagnoses differed largely between various diagnosis categories. Especially somatoform disorders and radicular syndromes were often newly diagnosed. CONCLUSION: A high number of second opinion and tertiary referral patients benefits from a day-care admission in a neurological outpatient clinic. Careful selection for referral of patients who will benefit from daycare admission may even enlarge the diagnostic and therapeutic yield.

[Treatment of acute ischemic stroke with intravenous thrombolysis: extension of the time window should not delay initiation of treatment]. / Behandeling van het acute herseninfarct met intraveneuze trombolyse: meer tijd, maar geen minuut te verliezen.

In the European Cooperative Acute Stroke Study 3 (ECASS3), the efficacy of intravenous thrombolysis between 3 and 4.5 hours following onset of ischaemic stroke was investigated. Compared to the placebo group, patients treated with intravenous alteplase had a better functional outcome after 3 months (odds ratio 1.34, 95% confidence interval 1.02-1.76). The risk of symptomatic intracerebral haemorrhage was higher in the alteplase group (2.4% versus 0.3%). The time window for intravenous alteplase can be safely extended to 4.5 hours, but efforts should be made to start treatment as soon as possible, since the effectiveness ofalteplase decreases over time.

[Clinical practice is the most important environment to acquire clinical knowledge]. / De kliniek is de voornaamste plaats om klinische kennis op te doen.

The amount of learning devoted to clinical teaching in medical schools is under pressure from increased amounts of time devoted to so-called 'basic sciences' and recent emphasis on non-medical competencies. Clinical teaching, in direct contact with real patients and supervised by experienced clinical teachers, should remain the core of medical education. Competing subjects should be regarded as important, but limited, corollaries.

Observer variation in the evaluation of lumbar herniated discs and root compression: spiral CT compared with MRI.

Spiral CT is considered the best alternative for MRI in the evaluation of herniated discs. The purpose of this study was to compare radiological evaluation of spiral CT with MRI in patients suspected of herniated discs. 57 patients with lumbosacral radicular syndrome underwent spiral CT and 1.5 T MRI. Two neuroradiologists independently evaluated 171 intervertebral discs for herniation or "bulge" and 456 nerve roots for root compression, once after CT and once after MRI. We compared interobserver agreement using the kappa statistic and we performed a paired comparison between CT and MRI. For detection of herniated or bulging discs, we observed no significant difference in interobserver agreement (CT kappa 0.66 vs MRI kappa 0.71; p = 0.40). For root compression, we observed significantly better interobserver agreement at MRI evaluation (CT kappa 0.59 vs MRI kappa 0.78; p = 0.01). In 30 of 171 lumbar discs (18%) and in 54 of 456 nerve roots (12%), the observers disagreed on whether CT results were similar to MRI. In the cases without disagreement, CT differed from MRI in 6 discs (3.5%) and in 3 nerve roots (0.7%). For radiological evaluation of lumbar herniated discs, we found no evidence that spiral CT is inferior to MRI. For evaluating lumbar nerve root compression, spiral CT is less reliable than MRI.

Symptomatic and asymptomatic abnormalities in patients with lumbosacral radicular syndrome: Clinical examination compared with MRI.

OBJECTIVE: To determine the frequency of symptomatic and asymptomatic herniated discs and root compression in patients with lumbosacral radicular syndrome (LRS) and to correlate clinical localization with MRI findings. METHODS: Fifty-seven patients with unilateral LRS were included in the study. Using the visual analogue scale, two physicians independently localized the most likely lumbar level of complaints. These clinical predictions of localizations were correlated with the MRI findings. RESULTS: MRI showed abnormalities on the symptomatic side in 42 of 57 patients (74%). In 30% of the patients, MRI confirmed an abnormality at the exact same level as determined after clinical examination. On the asymptomatic side, MRI showed abnormalities in 19 of 57 patients (33%), 13 (23%) of these patients had asymptomatic root compression. CONCLUSIONS: In more than two-thirds of the patients with unilateral LRS there was no exact match between the level predicted by clinical examination and MRI findings. These discrepancies complicate the decision whether or not to operate.

[Endarterectomy should not be offered routinely to patients with asymptomatic carotid stenosis]. / Endarteriëctomie niet routinematig aanbieden bij patiënten met een asymptomatische carotisstenose.

A recent trial revealed a reduction in ischaemic infarcts after carotid endarterectomy in patients with asymptomatic carotid stenosis. However, the number needed to treat (NNT) was 19 to prevent one stroke in 5 years, a modest effect in comparison to the trials with symptomatic patients (a NNT of only 6 in patients with a symptomatic stenosis of 70-99%). Furthermore, the number of surgical complications outweighs the benefits of surgery during the first two years after treatment. Finally, the benefits also included the prevention of contralateral strokes, whereas it is unlikely that these are prevented by endarterectomy. Therefore, endarterectomy should not be performed routinely in asymptomatic persons.

Plant-mediated interactions between two herbivores differentially affect a subsequently arriving third herbivore in populations of wild cabbage.

Plants are part of biodiverse communities and frequently suffer from attack by multiple herbivorous insects. Plant responses to these herbivores are specific for insect feeding guilds: aphids and caterpillars induce different plant phenotypes. Moreover, plants respond differentially to single or dual herbivory, which may cascade into a chain of interactions in terms of resistance to other community members. Whether differential responses to single or dual herbivory have consequences for plant resistance to yet a third herbivore is unknown. We assessed the effects of single or dual herbivory by Brevicoryne brassicae aphids and/or Plutella xylostella caterpillars on resistance of plants from three natural populations of wild cabbage to feeding by caterpillars of Mamestra brassicae. We measured plant gene expression and phytohormone concentrations to illustrate mechanisms involved in induced responses. Performance of both B. brassicae and P. xylostella was reduced when feeding simultaneously with the other herbivore, compared to feeding alone. Gene expression and phytohormone concentrations in plants exposed to dual herbivory were different from those found in plants exposed to herbivory by either insect alone. Plants previously induced by both P. xylostella and B. brassicae negatively affected growth of the subsequently arriving M. brassicae. Furthermore, induced responses varied between wild cabbage populations. Feeding by multiple herbivores differentially activates plant defences, which has plant-mediated negative consequences for a subsequently arriving herbivore. Plant population-specific responses suggest that plant populations adapt to the specific communities of insect herbivores. Our study contributes to the understanding of plant defence plasticity in response to multiple insect attacks.

Sequence of the human invasion-inducing TIAM1 gene, its conservation in evolution and its expression in tumor cell lines of different tissue origin.

By means of proviral tagging in combination with in vitro selection for invasive T-lymphoma variants, we have previously identified the murine invasion- and metastasis-inducing Tiam1 gene. Tiam1 encodes a novel protein which shares a Dbl-homology (DH) domain with GDP dissociation stimulator-(GDS) proteins that activate Rho-like GTPases. We have cloned the human TIAM1 coding sequence and studied its evolutionary conservation and expression pattern. TIAM1 is highly conserved among vertebrates. The close similarity between human TIAM1 and the mouse homologue is indicated by 88% and 95% identity of nucleotides and predicted sequences, respectively. The murine gene is highly expressed in brain and testis and at low or moderate levels in almost all other normal tissues. Interestingly, Tiam1 transcripts were found in virtually all analysed tumor cell lines of human and rodent origin including B- and T-lymphomas, neuroblastomas, melanomas and carcinomas. The evolutionary conservation as well as the broad expression pattern of Tiam1 in most normal tissues, suggests a general function in cellular signaling processes presumably by activation of a Rho-like GTPase that regulates the cytoskeletal organization.