Prospective study of the additional benefit of plexus magnetic resonance imaging in the diagnosis of chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: Hypertrophy/signal hyperintensity and/or gadolinium enhancement of plexus structures on magnetic resonance imaging (MRI) are observed in two-thirds of cases of typical chronic inflammatory demyelinating polyneuropathy (CIDP). The objective of our study was to determine the additional benefit of plexus MRI in patients referred to tertiary centers with baseline clinical and electrophysiological characteristics suggestive of typical or atypical CIDP. METHODS: A total of 28 consecutive patients with initial suspicion of CIDP were recruited in nine centers and followed for 2 years. Plexus MRI data from the initial assessment were reviewed centrally. Physicians blinded to the plexus MRI findings established the final diagnosis (CIDP or neuropathy of another cause). The proportion of patients with abnormal MRI was analyzed in each group. RESULTS: Chronic inflammatory demyelinating polyneuropathy was confirmed in 14 patients (50%), as were sensorimotor CIDP (n = 6), chronic immune sensory polyradiculoneuropathy (n = 2), motor CIDP (n = 1) and multifocal acquired demyelinating sensory and motor neuropathy (n = 5). A total of 37 plexus MRIs were performed (17 brachial, 19 lumbosacral and 8 in both localizations). MRI was abnormal in 5/37 patients (14%), all of whom were subsequently diagnosed with CIDP [5/14(36%)], after an atypical baseline presentation. With plexus MRI results masked, non-invasive procedures confirmed the diagnosis of CIDP in all but one patient [1/14 (7%)]. Knowledge of the abnormal MRI findings in the latter could have prevented nerve biopsy being performed. CONCLUSION: Systematic plexus MRI in patients with initially suspected CIDP provides little additional benefit in confirming the diagnosis of CIDP.

Preparation and characterization of activated carbon developed from cotton cloth residue activated with phosphoric acid: adsorption of clofibric acid.

Cotton cloth waste was used as a precursor to prepare activated carbon (ACCs) chemically activated with phosphoric acid. Adsorption behavior of prepared ACCs was correlated with physicochemical proprieties. The pore volume and BET surface of ACCs were determined by nitrogen adsorption isotherms and scanning electron microscopy was used to observe their surface morphologies. Fourier transform infrared (FTIR) spectroscopy analysis and pH point zero charge (pHPZC) were conducted to determine chemical properties. Under the optimal conditions: 50% impregnation ratio and thermal treatment under N2 flow at 600 °C during 60 min, the activated carbon prepared exhibits a high surface area 1,150 m2/g, 0.501 cm3/g micropore volume and an excellent adsorption performance. The adsorbed amount of clofibric acid is found to be 9.98 and 83 mg/g at, respectively, initial CA concentration of 10 and 100 mg/L at pH 3.0 and 20 °C. Diffusion and chemisorption are the steps controlling the adsorption of CA onto ACC 50% and the equilibrium data were well described by Freundlich isotherm.

High dose subcutaneous immunoglobulin for idiopathic inflammatory myopathies and dysimmune peripheral chronic neuropathies treatment: observational study of quality of life and tolerance.

BACKGROUND: In patients with autoimmune diseases who still derive benefit from high dose intravenous immunoglobulin (IVIg) treatment, some physicians resort to subcutaneous (SC) Ig as a replacement therapy. OBJECTIVE: To collect quality of life (QoL) and tolerance data on SCIg in patients for whom the switch from IVIg to SCIg is essential to maintain treatment. METHODS: This observational study included patients with either idiopathic inflammatory myopathies (IIM) or chronic dysimmune peripheral neuropathies (CDPN) treated with IVIg, who had been switched to SCIg administration for at least three months. The main objective was to describe the impact of SCIg on QoL after six months, using the generic Short-Form 36 questionnaire (SF-36). The secondary objectives were to evaluate SCIg tolerance and clinical efficiency. RESULTS: Eight centres recruited 12 IIM patients and two centres recruited 11 CDPN patients. Neither the physical nor the mental health SF-36 component summaries showed any QoL deterioration during the six-month study period and all IIM and CDPN patients remained clinically stable during the same period. The most frequent adverse effects were injection site reactions (50%), cutaneous tissue disorders (18.2%), and nervous system disorders (13.6%). Two serious adverse events (myocarditis and cerebrovascular accident) occurred in two patients. CONCLUSION: In these rare inflammatory diseases, high dose SCIg administration (which can be home based) has no deleterious effect on patient QoL. It appears to be a safe and efficient alternative to hospital-based IVIg.

Evaluation of the application of the European guidelines for the diagnosis and clinical care of amyotrophic lateral sclerosis (ALS) patients in six French ALS centres.

BACKGROUND AND PURPOSE: Our objective was to evaluate the extent to which the 2005 recommendations of the European Federation of Neurological Sciences (EFNS) on the multidisciplinary management of amyotrophic lateral sclerosis (ALS) are followed in clinical practice. METHODS: This was a multicentre observational study involving six French ALS referral centres receiving prevalent and incident cases. Recommendations were translated into ad hoc questions referring to key aspects of management, and their application was evaluated by a clinical research assistant who independently examined the medical charts (MCs). When necessary, an independent board-certified neurologist answered the questions based on examination of the MC and interview of the caring neurologist. Questions regarding diagnosis and communication were put to patients in a self-administered questionnaire. RESULTS: In all, 376 patients [176 incident, 200 prevalent cases; median age at diagnosis 62.8 years (interquartile range 55.7-72.3); sex ratio 1.37; 27.3% bulbar onset] were included. All the topics covered in the recommendations were evaluated: diagnostic delay (e.g. mean 13.6 months, associated with age and onset); breaking the news (e.g. criteria for communication quality were satisfactory in more than 90%); multidisciplinary and sustained support (e.g. clinic visits were scheduled every 2-3 months in 90%). Also considered were whether riluzole had been offered, symptom management, genetic testing, ventilation, communication defects, enteral nutrition, palliative and end-of-life care. Characteristics associated with poor compliance with some guidelines (schedule of visits, delayed riluzole initiation) were also identified. CONCLUSION: This is the first evaluation of the application of the EFNS recommendations for the management of ALS in a nationwide sample. The results allow us to highlight areas for improvement.

Antibodies to clustered acetylcholine receptor: expanding the phenotype.

BACKGROUND AND PURPOSE: To provide a detailed phenotypical description of seronegative patients with generalized myasthenia gravis and antibodies to clustered acetylcholine receptors (AChRs) and to assess their frequency amongst a French seronegative generalized myasthenia gravis (SNMG) population. METHODS: A French SNMG database was created and the sera from the 37 patients included in it were analysed by immunofluorescence of cell-based assays using cotransfection of AChR subunit genes together with rapsyn to densely cluster the AChRs. RESULTS: Sixteen per cent (n = 6) of the SNMG patients were found to have antibodies to clustered AChR. They presented either with early onset MG and thymic hyperplasia, late onset MG and thymic involution, or thymoma associated MG. They responded well to cholinesterase inhibitors and immunosuppressants. CONCLUSIONS: Patients with antibodies to clustered AChR account for a significant proportion of SNMG patients and resemble patients with AChR antibodies detected by standard radio-immunoprecipitation.

Food aeration: Effect of the surface-active agent type on bubble deformation and break-up in a viscous Newtonian fluid: From single bubble to process-scale.

Two continuous whipping devices, a rotor-stator (RS) and a narrow angular gap unit (NAGU), were used to produce aerated food with a 25% (v/v) gas fraction target. The liquid phase was a Newtonian model-solution containing 2% (w/w) of either whey proteins (WPC), sodium caseinate (SCN), or tween 20 (TW20). Strong differences emerged regarding gas incorporation and bubble size as a function of process parameters: namely, rotation speed and residence time. To improve understanding of the results obtained at pilot-scale, a second investigation consisting in the observation of the deformation and break-up of single gas bubbles has been undertaken using successively a Couette device and an impeller close to NAGU. For proteins, the observation of single bubble deformation and break-up showed that bubble break-up occurred by tip-streaming above a well-defined critical Capillary number Cac of 0.27 and 0.5 for SCN and WPC, respectively, whereas no break-up was observed with TW20 even though Ca reached 10. The poor foaming ability obtained with TW20 could be explained by a poor break-up mechanism, promoting coalescence and gas plugs at high shear instead of gas incorporation. Conversely, protein promote tip-streaming as the major break-up mechanism at low shear rate, explaining why rotation speed is not a key process parameter. Differences observed between SCN and WPC can be attributed to diffusion limitation for SCN when a much larger surface area is generated during aeration.

[Viral etiology of community acquired pneumonia among adults admitted to a general hospital]. / Etiología viral en la neumonía del adulto adquirida en la comunidad en un hospital del sur de Chile.

BACKGROUND: There is paucity of information about viral etiology of community acquired pneumonia in adults. AIM: To investigate the viral etiology of pneumonia among hospitalized patients. MATERIAL AND METHODS: All adults with pneumonia that were hospitalized were prospectively enrolled at Puerto Montt hospital. A microbiological and viral assessment was carried out. Viral assessment included direct immunofluorescence of nasopharyngeal aspirates for influenza A and B virus and serum samples obtained during the acute phase of the disease and during convalescence for Hanta virus. RESULTS: Between April 1 2005 and March 31 2006,159 adults aged 62 ± 20 years (58 % males), were admitted to the hospital for pneumonia. Mean hospital stay was 11.9 ± 8.6 days. Four patients had Hantavirus acute infection. Other viruses were identified in twelve patients (7.7%). Nine had influenza A, one syncytial respiratory virus, one syncytial and influenza A virus and one varicella zoster virus. Excluding patients with Hantavirus, no significant differences in age, clinical presentation, chest X ray findings, laboratory results and mortality were observed between patients with bacterial or viral etiology of the pneumonia. CONCLUSIONS: Viral etiology was confirmed in 10% of adult patients hospitalized with community acquired pneumonia.

Voltage-gated sodium channel expression in rat spiral ganglion neurons.

The spiral ganglion neurons (SGN) provide the afferent innervation of the hair cells in the organ of Corti and relay auditory information from the inner ear to the brain. Voltage-gated sodium channels (Na(V)) initiate and propagate action potentials that encode this sensory information but little is known regarding the subtypes expressed in these cells. We have used RT-PCR and immunohistochemistry to study the compliment and anatomical distribution of Na(V) channels in rodent SGN. Na(V)1.1, Na(V)1.6 and Na(V)1.7 were all detected at the mRNA level. Fluorescence or streptavidin-horseradish peroxidase immunohistochemistry extended these findings, demonstrating predominant localisation of Na(V)1.6 and Na(V)1.7 on SGN cell bodies and Na(V)1.1 on axonal processes. Dual labelling with peripherin demonstrated higher Na(V)1.6 and Na(V)1.7 expression on Type I rather than Type II neurons. These results provide evidence for selective expression and variations in the distribution of VGSC in the rodent SGN, which may guide further studies into afferent function in the auditory pathway and therapeutic approaches for diseases such as hearing loss and tinnitus.

[Hantavirosis: clinical and epidemiological characteristics of pediatric patients in Chile]. / Hantavirosis: Caracterización clínica-epidemiológica de pacientes pediátricos en Chile.

BACKGROUND: The first cases of Hantavirus cardiopulmonary syndrome in children were described in the United States and represented 8% of the total reported cases; in Chile, the proportion of pediatric cases represents 15% of all national cases. AIM: To describe the epidemiology and clinical course of 82 children reported to the Chilean Ministry of Health up to 2007 and to characterize more extensively a subgroup of 24 children whose detailed clinical data were available. RESULTS: Forty patients were under 10 years old. Seventeen (17/82) of 82 cases (20.7%) presented in the context of a family cluster. Ninety eight percent of cases (80/82) occurred among individuals living in rural areas and 66% during summer months). The overall fatality rate was 36.6%. Fever (93%), respiratory distress (75%) and gastrointestinal symptoms (75%) were the most frequent symptoms encountered in the 28 children studied more extensively. Abnormal blood coagulation test were significantly associated with death while an increased hematocrit was associated with severe cases (hemodynamic unstability). CONCLUSION: An early diagnosis should favor early onset of aggressive treatment that could potentially save lives. Increasing knowledge on the clinical presentation of the disease in children should improve early clinical diagnosis among health care professionals.

Ulnar neuropathy at the elbow: Reappraisal of the wrist-upper arm latency difference between ulnar and median nerves.

OBJECTIVES: To evaluate the sensitivity and specificity of the latency difference (DLat) between ulnar and median nerves of the arm after stimulation at the wrist; one of the easiest techniques proposed for recognizing ulnar neuropathy at the elbow (UNE). As latency difference is not a standardized technique, we set up a multicenter study to recruit large numbers of normal subjects and patients with UNE or generalized neuropathy. METHODS: Six centers participated in the study with data obtained from three groups of participants, controls (CTRLs), patients with UNE and patients with generalized neuropathy (GNP). We first verified the anatomical superposition of the ulnar and median nerves in cadaver examination. The optimal recording site for these two nerves was found to be 10 cm above the medial epicondyle. We then standardized the position of the arm with full extension of the elbow and stimulated first the median and then the ulnar nerves at the wrist. CTRLs were examined on both arms at two consecutive visits. RESULTS: We recorded 32 idiopathic UNE cases, 44 GNP patients and 62 controls. We demonstrated that a DLat cut-off value of 0.69 ms brings a sensitivity of 0.86 and specificity of 0.89 to discriminate CTRLs from UNE. We also validated that intra-examiner reproducibility was good. CONCLUSION: We report a lower normal value for DLat than reported in several non-standardized studies and CTRL and UNE groups have clearly separated DLat values. SIGNIFICANCE: Due to its high sensitivity, our standardized technique could be used as a first-line diagnostic tool when UNE is suspected.

[Value of electroneuromyography in the diagnosis and follow-up of myasthenia gravis]. / Interet de l'electroneuromyographie dans le diagnostic et le suivi des myasthenies.

The diagnosis of myasthenia gravis is above all clinical, however electroneuromyography (ENMG) and laboratory tests can be helpful. ENMG testing is readily available and with immediate results. Useful with emergent symptoms, it is equally so in the event of more acute pictures found in generalized motor deficit and bulbar findings of respiratory failure. It can be performed in out-patient clinics or at the bedside. ENMG is based on an assessment of repetitive nerve stimulations (RNS), which can be sensitized, and more rarely on jiter studies using single-fiber electromyography (SFEMG). RNS recordings from multiple sites, depending on symptoms, are preferable. The usefulness of these tests varies depending on the clinical situation, not only for diagnosis but also during follow-up, in order to obtain objective evidence of the effects of treatment.

[Molecular diagnosis of axonal forms of Charcot-Marie-Tooth disease]. / Diagnostic moléculaire des formes axonales de la maladie de Charcot-Marie-Tooth.

Charcot-Marie-Tooth (CMT) disease is the most common cause of inherited peripheral neuropathies with a frequency estimated at 1/2500. Electroneuromyographic examination distinguishes a myelinic form (CMT1) and an axonal form of the disease (CMT2). Significant genetic heterogeneity is found in CMT, with 15 genes or loci for CMT2. To date, a molecular diagnosis has not been established for most CMT2 patients and the distribution of identified mutations is wide spreading over nearly all genes. Simple guidelines for daily practice are difficult to establish from compilation of mutation reports or consultation of databases; little simplification can be expected from future findings. We present our results of molecular diagnosis for 251 CMT2 index cases characterized by their mode of inheritance (217 dominant and 34 recessive cases), and a motor conduction velocity in median nerve equal to or above to 38m/s. For each case, at least one of the genes known to date for CMT2 (MFN2, RAB7, GARS, NF-L, HSPB1, GDAP1, MPZ, HSPB8, GJB1, DNM2, YARS, LMNA, and MED25) was studied. Around 22% of diagnoses were established and efficiency was comparable for dominant or recessive cases. For dominant cases, the first objective was to search for mutations of proteins connexin32, mitofusin2 and P0. For recessive cases, GDAP1 provided the key to molecular diagnosis; lamin A/C mutations were only found for patients with an ethnic background from North Africa. Heat shock proteins HSPB1 and HSPB8 were implicated in a significant proportion of "spinal" (or pure motor) CMT2. NF-L or RAB7 mutations were rare. We did not identify any deleterious mutations in GARS, DNM2, YARS orMED2. We propose a simple decision tree for molecular diagnosis of CMT2.

[Multiple phenotypic manifestations of X-linked spinobulbar muscular atrophy]. / L'amyotrophie bulbospinale liée à l'X ou maladie de Kennedy: variations phénotypiques.

Recessive X-linked amyotrophic spinobulbar muscular atrophy (SBMA) or Kennedy disease is a neuroendocrine disorder with a slowly progressive phenotype, caused by an expansion of a polymorphic tandem CAG repeat of the androgen receptor gene. Classical clinical hallmarks include onset in the third decade of life, weakness and wasting predominantly in proximal extremity muscles, variable weakness of bulbar muscles, abundant muscle fasciculations, sensory nerve action potential abnormalities and signs of androgen insensitivity such as gynecomastia and testicular atrophy. The diagnosis has been recently made easier by the availability of genetic testing but Kennedy disease is probably still underdiagnosed because of phenotypic variability. We report 11 new cases, of which seven had atypical initial manifestations presenting respectively with myasthenia, cramps and fasciculation syndrome, polyneuropathy, post-trauma monomelic neuronopathy, effort-dependent muscle intolerance and/or muscular dystrophy, with the aim to enlarge the phenotypic spectrum of the published series.

[Electrophysiological monitoring of cranial motor nerves (V, VII, IX, X, XI, XII)]. / Evaluation électrophysiologique des nerfs crâniens moteurs (V, VII, IX, X, XI, XII).

In various neurosurgical operations, there is a risk of cranial nerve lesion that can be avoided or minimized with intraoperative electrophysiological monitoring. Regarding motor function of the cranial nerves, stimulodetection techniques are used, including electrical stimulation of nerve trunks and electromyographic recording of evoked motor responses. These techniques can be used for monitoring the trigeminal nerve (Vth cranial nerve), facial nerve (VIIth), glossopharyngeal nerve (IXth), pneumogastric nerve (Xth), spinal accessory nerve (XIth), and hypoglossal nerve (XIIth), in particular during surgical removal of tumors of the cerebellopontine angle or skull base. When beginning an operation, electrical stimulation is only used to identify the nerve structures. As removal of the tumor progresses, the goal is to verify that a surgical injury to the nerve is avoided by looking for the absence of any change regarding amplitude, morphology, and latency of motor responses. Intraoperative electromyographic monitoring can also be applied during the surgical treatment of primary hemifacial spasm by microvascular decompression. An effective decompression is usually associated with the disappearance of "lateral spread" motor responses to facial nerve branch stimulation. Therefore, the intraoperative disappearance of the lateral spread responses can be considered a predictive factor of good postoperative clinical outcome, even if this assertion remains a matter of debate.

Dilated cardiomyopathy and limb-girdle muscular dystrophy-dystroglycanopathy due to novel pathogenic variants in the DPM3 gene.

Deficiency of Dolichol-P-mannose synthase subunit 3 (DPM3) affects the N-glycosylation and O-mannosylation pathways that are respectively involved in congenital disorders of glycosylation (CDG) and alpha-dystroglycanopathies. Herein, we describe novel pathogenic variants in the DPM3 gene in two unrelated male patients. They developed dilated cardiomyopathy in their late teens, limb-girdle muscular dystrophy - one patient in childhood and the other in adulthood. In both patients, next generation sequencing found in the DPM3 gene a heterozygous deletion and a heterozygous pathogenic missense mutation in exon 2 (c.41T>C, p.Leu14Pro). Electrophoresis of serum transferrin found an abnormal N-glycosylation profile suggestive of CDG type 1 (decreased tetrasialotransferrin, increased disialo- and asialotransferrin). Only two cases of DPM3 gene mutations with limb-girdle muscular dystrophy-dystroglycanopathy have been reported previously. The present study highlights several aspects related to DPM3 gene mutations such as mild to moderately severe limb-girdle muscular dystrophy, dilated cardiomyopathy, and abnormal N-glycosylation profile suggestive of CDG type 1.

[Sociodemographic risk factors of hantavirus cardiopulmonary syndrome]. / Factores de riesgo socio-demográficos del síndrome cardiopulmonar por hantavirus.

BACKGROUND: Hantavirus cardiopulmonary syndrome (HCPS) is caused by new world hantaviruses, among which Andes hantavirus (ANDV) is endemic to Chile and Southern Argentina. The disease caused by ANDV produces plasma leakage leading to enhanced vascular permeability and has a high case fatality rate (35%), mainly due to respiratory failure, pulmonary edema and myocardial dysfunction, hypoperfusion and shock. Host sociodemographic and genetic factors might influence the course and outcome of the disease. Yet, they have not been thoroughly characterized. AIM: To evaluate sociodemographic factors as risk factors in severity of HCPS. PATIENTS AND METHODS: Study period: 2004-20013, attending in eight collaborative centers, etiological diagnosis was performed by serology or molecular biology, mild and severe HCPS were compared.139 Chilean patients were analyzed, 64 (46%) with severe disease among which 12 (19 %) died. RESULTS: European ethnicity had 5,1 times higher risk than Amerindian ethnic group to develop a severe HCPS, greater seriousness that was also associated with an urban residence. CONCLUSION: It was observed that ethnicity and type of residence were significant risk factors for HCPS severity. Hypotheses explaining these findings are discussed.

Is the early-onset torsion dystonia (EOTD) linked to TOR1A gene as frequent as expected in France?

Early onset torsion dystonia are rare movement disorders. Molecular defect is known for only a subgroup, consisting of a unique and recurrent mutation in the TOR1A gene. We undertook a nationwide census of French TOR1A-mutation carriers and the assessment of clinical associated signs. Overall, 53 index cases and 104 relatives were studied and haplotypes linked to the mutation constructed. The previously reported Ashkenazi-Jewish haplotype was found in 11 families with the remainder carrying distinct haplotypes suggesting independent mutation events. This study demonstrates the scarcity of this disease in France with estimated disease frequency of 0.13:100,000 and mutation frequency of 0.17:100,000.

Factors predicting survival following noninvasive ventilation in amyotrophic lateral sclerosis.

BACKGROUND/AIMS: The involvement of respiratory muscles is a major predicting factor for survival in amyotrophic lateral sclerosis (ALS). Recent studies show that noninvasive ventilation (NIV) can relieve symptoms of alveolar hypoventilation. However, factors predicting survival in ALS patients when treated with NIV need to be clarified. METHODS: We conducted a retrospective study of 33 consecutive ALS patients receiving NIV. Ten patients had bulbar onset. We determined the median survivals from onset, diagnosis and initiation of NIV and factors predicting survival. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. RESULTS: The median initial and maximal total uses of NIV were 10 and 14 h/24h. The overall median survival from ALS onset was 34.2 months and worsened with increasing age and bulbar onset of the disease. The median survival from initiation of NIV was 8.4 months and was significantly poorer in patients with advanced age or with airway mucus accumulation. Survival from initiation of NIV was not influenced by respiratory parameters or bulbar symptoms. CONCLUSION: Advanced age at diagnosis and airway mucus accumulation represent poorer prognostic factors of ALS patients treated with NIV. NIV is a helpful treatment of sleep-disordered breathing, including patients with bulbar involvement.

[Listeria monocytogenes: report of a rise in pregnant women and literature review]. / Listeria monocytogenes: Informe de un aumento de casos en mujeres embarazadas y revisión de la literatura.

Listeria monocytogenes, rare pathogen in the general population, causes serious infections in patients at the extreme ages of life, pregnant woman, and those with immunosuppression. The clinical manifestations are essential to suspect the disease in patients at risk, allowing an early prescription of antimicrobial therapy, before the results of the cultures are available. Clinical course and prognosis depends on how early treatment is started and, in pregnant women, the gestational age. In Clínica Alemana, at Santiago, we detected a 15 fold rate rise of neonatal listeriosis between year 2007 and 2008. Ten cases were diagnosed between January and July 2008 and the seven cases occurring in pregnant women are reported here. All these patients were in their first pregnancy, which could be associated with similar lifestyle and food habits. Considering this new epidemiological scenario, it is important to educate the population, and to conduct an epidemiological study in order to determine the national situation of Listeria monocytogenes infection.

Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y(1) receptor-null mice.

ADP is a key agonist in hemostasis and thrombosis. ADP-induced platelet activation involves the purinergic P2Y(1) receptor, which is responsible for shape change through intracellular calcium mobilization. This process also depends on an unidentified P2 receptor (P2cyc) that leads to adenylyl cyclase inhibition and promotes the completion and amplification of the platelet response. P2Y(1)-null mice were generated to define the role of the P2Y(1) receptor and to determine whether the unidentified P2cyc receptor is distinct from P2Y(1). These mice are viable with no apparent abnormalities affecting their development, survival, reproduction, or the morphology of their platelets, and the platelet count in these animals is identical to that of wild-type mice. However, platelets from P2Y(1)-deficient mice are unable to aggregate in response to usual concentrations of ADP and display impaired aggregation to other agonists, while high concentrations of ADP induce platelet aggregation without shape change. In addition, ADP-induced inhibition of adenylyl cyclase still occurs, demonstrating the existence of an ADP receptor distinct from P2Y(1). P2Y(1)-null mice have no spontaneous bleeding tendency but are resistant to thromboembolism induced by intravenous injection of ADP or collagen and adrenaline. Hence, the P2Y(1) receptor plays an essential role in thrombotic states and represents a potential target for antithrombotic drugs.