Safety of bone marrow aspiration and biopsy in severely thrombocytopenic patients.

PURPOSE: To assess the safety of fluoroscopically guided drill-assisted bone marrow aspirate and biopsy in severely thrombocytopenic patients. MATERIALS AND METHODS: The study was approved by the IRB with waiver of informed consent. Retrospective review of 111 bone marrow aspirate and biopsies (BMAB) performed in 94 patients who received a CT scan which included the pelvis and biopsy site within the 7 days following the BMAB. The 94 patients were subdivided based on their platelet count: severe thrombocytopenia (< 20 platelets × 109/L), thrombocytopenia (20-50 platelets × 109/L), and control (> 50 platelets × 109/L). The procedure report was reviewed for sedation time, aspirate volume, and aggregate size of core biopsy specimens. The electronic medical record was reviewed for specimen adequacy; pathologic diagnosis; body mass index; pre- and post-procedure labs including platelet count, hemoglobin (HGB), hematocrit (HCT), prothrombin time (PT), and international normalized ratio (INR) levels; post-procedural transfusion; and complications including mortality at 30 and 90 days. CT scans were independently reviewed by 2 fellowship-trained radiologists for the presence of post-procedural hemorrhage. RESULTS: There was no significant difference in CT-identified post-procedural hematoma, or change in the hemoglobin and hematocrit levels pre- and post-procedure between the three groups. There was no significant difference in complication rate or all-cause mortality. There was a significant difference in transfusion at 30 days with thrombocytopenic and severely thrombocytopenic patients more likely to receive transfusion within the 30 days post-procedure. CONCLUSION: Fluoroscopically guided BMAB can be safely performed in patients with severe thrombocytopenia.

Percutaneous CT-Guided Core Needle Biopsies of Head and Neck Masses: Technique, Histopathologic Yield, and Safety at a Single Academic Institution.

BACKGROUND AND PURPOSE: CT-guided head and neck biopsies can be challenging due to the anatomy and adjacent critical structures but can often obviate the need for open biopsy. A few studies and review articles have described approaches to biopsy in the head and neck. This retrospective study evaluated technical considerations, histopathologic yield, and safety in CT-guided head and neck core needle biopsies. MATERIALS AND METHODS: A retrospective review of head and neck biopsies performed from January 2013 through December 2019 was conducted. Clinical diagnosis and indication, patient demographics, mass location and size, biopsy needle type, technical approach, dose-length product, sedation details, complications, diagnostic histopathologic yield, and the use of iodinated contrast were recorded for each case. RESULTS: A total of 27 CT-guided head and neck core needle biopsies were performed in 26 patients. The diagnostic sample rate was 100% (27/27). A concordant histopathologic diagnosis was obtained in 93% (25/27) of cases. There was a single complication of core needle biopsy, a small asymptomatic superficial hematoma. CONCLUSIONS: Percutaneous CT-guided biopsy of deep masses in the head and neck is safe and effective with careful biopsy planning and has a high diagnostic yield that can obviate the need for open biopsy.

Percutaneous CT-Guided Skull Biopsy: Feasibility, Safety, and Diagnostic Yield.

BACKGROUND AND PURPOSE: Although percutaneous musculoskeletal biopsies are routinely performed in the axial and appendicular skeleton, there are no published data on the systematic evaluation of the feasibility, safety, and diagnostic accuracy of percutaneous skull biopsy. In certain clinical encounters such as patients with primary skull tumors or patients with known cancer and isolated skull lesions suspected of calvarial metastasis or synchronous primary tumor, percutaneous skull biopsy may be considered a viable option. The purpose of this study was to evaluate the feasibility, safety profile, and diagnostic yield of percutaneous CT-guided skull biopsy. MATERIALS AND METHODS: Percutaneous CT-guided skull biopsy was performed in 14 patients. Patient demographics, cancer history, indication for initial imaging, imaging technique of diagnosis, skull tumor anatomic location, and final histologic diagnosis were documented. Preprocedural imaging of each skull lesion was reviewed to determine tumor size and characteristics. Procedural notes were reviewed to determine the total conscious sedation time or anesthesia time, type of biopsy needle, and the number and length of obtained core specimens. Procedure-related complications were also documented according to the Society of Interventional Radiology classification. RESULTS: All CT-guided percutaneous skull biopsy procedures were performed as preoperatively planned and were technically successful. Procedures were performed with the patient under conscious sedation in 93% (13/14) of cases. Definitive histologic diagnosis was achieved in 86% (12/14) of cases. There were no acute or delayed procedure-related complications. CONCLUSIONS: The results of this retrospective initial study suggest that percutaneous CT-guided skull biopsy is feasible with an excellent safety profile, affords a high diagnostic yield for histologic characterization, and may obviate more invasive open skull biopsies.

Simultaneous Bipedicular Radiofrequency Ablation Combined with Vertebral Augmentation for Local Tumor Control of Spinal Metastases.

BACKGROUND AND PURPOSE: Percutaneous radiofrequency ablation combined with vertebral augmentation has emerged as a minimally invasive treatment for patients with vertebral metastases who do not respond to or have contraindications to radiation therapy. The prevalence of posterior vertebral body metastases presents access and treatment challenges in the unique anatomy of the spine. The purpose of this study was to evaluate the safety and efficacy of simultaneous bipedicular radiofrequency ablation using articulating bipolar electrodes combined with vertebral augmentation for local tumor control of spinal metastases. MATERIALS AND METHODS: Imaging-guided simultaneous bipedicular radiofrequency ablation combined with vertebral augmentation was performed in 27 patients (33 tumors) with vertebral metastases selected following multidisciplinary consultations, to achieve local tumor control in this retrospective study. Tumor characteristics, procedural details, and complications were documented. Pre- and postprocedural cross-sectional imaging was evaluated to assess local tumor control rates. RESULTS: Thirty-three tumors were successfully ablated in 27 patients. Posterior vertebral body or pedicle involvement or both were present in 94% (31/33) of cases. Sixty-seven percent (22/33) of the tumors involved ≥75% of the vertebral body volume. Posttreatment imaging was available for 79% (26/33) of the treated tumors. Local tumor control was achieved in 96% (25/26) of tumors median imaging follow up of 16 weeks. No complications were reported, and no patients had clinical evidence of metastatic spinal cord compression at the treated levels. CONCLUSIONS: Simultaneous bipedicular radiofrequency ablation combined with vertebral augmentation is safe and effective for local tumor control of vertebral metastases. Articulating bipolar electrodes enable the placement and proximity necessary for optimal confluence of the ablation zones. Local tumor control may lead to more durable pain palliation, prevent disease progression, and reduce skeletal-related events of the spine.

Percutaneous CT-Guided Biopsies of the Cervical Spine: Technique, Histopathologic and Microbiologic Yield, and Safety at a Single Academic Institution.

BACKGROUND AND PURPOSE: Cervical spine biopsies can be challenging due to the anatomy and the adjacent critical structures. Percutaneous image-guided biopsies can obviate the need for an open biopsy, however there have been few studies looking at the approaches, safety, and efficacy of percutaneous cervical spine biopsies. This retrospective study evaluated technical considerations, histopathologic and microbiologic yield, and safety in CT-guided cervical bone biopsies. MATERIALS AND METHODS: A retrospective review of cervical bone and/or bone/disc biopsies performed from January 2010 to January 2017 was included in this study. Clinical diagnosis and indication, patient demographics, biopsy location, biopsy needle type, technical approach, lesion size, dose-length product, conscious sedation details, complications, and diagnostic histopathologic and/or microbiologic yield were recorded for each case and summarized. RESULTS: A total of 73 patients underwent CT-guided cervical bone biopsies. Fifty-three percent (39/73) were for clinical/imaging concern for infection and 47% (34/73) were for primary tumors or metastatic disease. Thirty-four percent (25/73) were of the inferior cervical spine (ie, C6 and C7). A sufficient sample was obtained for histopathologic and microbiologic analyses in 96% (70/73) of the biopsies. Forty-six percent (18/39) of those samples taken for infection had positive cultures. Two intraprocedural complications occurred in which the patients became hypotensive during the procedure without long-term complications. CONCLUSIONS: Percutaneous CT-guided biopsy of the cervical spine is an effective and safe procedure with high diagnostic yield and can obviate open procedures for histopathologic and microbiologic analyses of patients with clinical and imaging findings concerning for infection or primary and metastatic osseous lesions.

Percutaneous Spinal Ablation in a Sheep Model: Protective Capacity of an Intact Cortex, Correlation of Ablation Parameters with Ablation Zone Size, and Correlation of Postablation MRI and Pathologic Findings.

BACKGROUND AND PURPOSE: Despite the growing use of percutaneous ablation therapy for the treatment of metastatic spine disease, several issues have yet to be fully addressed. Our aims were to determine whether the vertebral body cortex protects against ablation-induced spinal cord injury; correlate radiofrequency, cryo-, and microwave ablation parameters with resulting spinal ablation zone dimensions and describe normal spinal marrow postablation changes on MR imaging. MATERIALS AND METHODS: Ten thoracolumbar vertebrae in 3 sheep were treated with radiofrequency ablation, cryoablation, or microwave ablation under fluoroscopic guidance. Technique parameters were chosen to produce ablation zones that exceeded the volume of the vertebral bodies in sheep 1 and were confined to the vertebrae in sheep 2 and 3. Expected ablation zone dimensions were based on data provided by the device manufacturers. Postablation MR imaging was performed at 48 hours (sheep 1) or 7 days (sheep 2 and 3). RESULTS: In sheep 1, cryoablation and microwave ablations extended into the spinal canal and caused histologically confirmed neurologic injury, but radiofrequency ablation did not. The mean difference between the lengths of the radiofrequency ablation zone dimensions measured on gross pathology compared with those expected was 9.6 ± 4.1 mm. The gross pathologic cryo- and microwave ablation zone dimensions were within 1 mm of those expected. All modalities produced a nonenhancing ablation zone with a rim of enhancement, corresponding histologically to marrow necrosis and hemorrhagic congestion. CONCLUSIONS: An intact cortex appears to protect against radiofrequency ablation-induced spinal cord injury, but not against non-impedance-based modalities. Ablation dimensions produced by microwave and cryoablation are similar to those expected, while radiofrequency ablation dimensions are smaller. Ablation of normal marrow produces a rim of enhancement at the margin of the ablation zone on MR imaging.

A non-local model for cancer stem cells and the tumour growth paradox.

The tumour growth paradox refers to the observation that incomplete treatment of cancers can enhance their growth. As shown here and elsewhere, the existence of cancer stem cells (CSCs) can explain this effect. CSC are less sensitive to treatments, hence any stress applied to the tumour selects for CSC, thereby increasing the fitness of the tumour. In this paper, we use a mathematical model to understand the role of CSC in the progression of cancer. Our model is a rather general system of integro-differential equations for tumour growth and tumour spread. Such a model has never been analysed, and we prove results on local and global existence of solutions, their uniqueness and their boundedness. We show numerically that this model exhibits the tumour growth paradox for all parameters tested. This effect becomes more relevant for small renewal rate of the CSC.

Spine Cryoablation: Pain Palliation and Local Tumor Control for Vertebral Metastases.

BACKGROUND AND PURPOSE: Percutaneous cryoablation has emerged as a minimally invasive technique for the management of osseous metastases. The purpose of this study was to assess the safety and effectiveness of percutaneous imaging-guided spine cryoablation for pain palliation and local tumor control for vertebral metastases. MATERIALS AND METHODS: Imaging-guided spine cryoablation was performed in 14 patients (31 tumors) with vertebral metastases refractory to conventional chemoradiation therapy or analgesics, to achieve pain palliation and local tumor control in this retrospective study. Spinal nerve and soft-tissue thermal protection techniques were implemented in all ablations. Patient response was evaluated by a pain numeric rating scale administered before the procedure and 1 week, 1 month, and 3 months after the procedure. Pre- and postprocedural analgesic requirements (expressed as morphine-equivalent dosages) were also analyzed at the same time points. Pre- and postprocedural cross-sectional imaging was evaluated in all patients to assess local control (no radiographic evidence of disease at the treated sites). Complications were monitored. Analysis of the primary end points was undertaken via paired-comparison procedures by using the Wilcoxon signed rank test. RESULTS: Thirty-one tumors were ablated in 14 patients (9 women and 5 men; 20-73 years of age; mean age, 53 years). The most common tumor location was in the lumbar spine (n = 14, 45%), followed by the thoracic spine (n = 8, 26%), sacrum (n = 6, 19%), coccyx (n = 2, 6%), and cervical spine (n = 1, 3%). There were statistically significant decreases in the median numeric rating scale score and analgesic usage at 1-week, 1-month, and 3-month time points (P < .001 for all). Local tumor control was achieved in 96.7% (30/31) of tumors (median follow-up, 10 months). Two patients had transient postprocedural unilateral lower extremity radiculopathy and weakness. CONCLUSIONS: Percutaneous imaging-guided spine cryoablation is a safe and effective treatment for pain palliation and local tumor control for vertebral metastases.

Birth-jump processes and application to forest fire spotting.

Birth-jump models are designed to describe population models for which growth and spatial spread cannot be decoupled. A birth-jump model is a nonlinear integro-differential equation. We present two different derivations of this equation, one based on a random walk approach and the other based on a two-compartmental reaction-diffusion model. In the case that the redistribution kernels are highly concentrated, we show that the integro-differential equation can be approximated by a reaction-diffusion equation, in which the proliferation rate contributes to both the diffusion term and the reaction term. We completely solve the corresponding critical domain size problem and the minimal wave speed problem. Birth-jump models can be applied in many areas in mathematical biology. We highlight an application of our results in the context of forest fire spread through spotting. We show that spotting increases the invasion speed of a forest fire front.

Mathematical modelling of glioma growth: the use of Diffusion Tensor Imaging (DTI) data to predict the anisotropic pathways of cancer invasion.

The nonuniform growth of certain forms of cancer can present significant complications for their treatment, a particularly acute problem in gliomas. A number of experimental results have suggested that invasion is facilitated by the directed movement of cells along the aligned neural fibre tracts that form a large component of the white matter. Diffusion tensor imaging (DTI) provides a window for visualising this anisotropy and gaining insight on the potential invasive pathways. In this paper we develop a mesoscopic model for glioma invasion based on the individual migration pathways of invading cells along the fibre tracts. Via scaling we obtain a macroscopic model that allows us to explore the overall growth of a tumour. To connect DTI data to parameters in the macroscopic model we assume that directional guidance along fibre tracts is described by a bimodal von Mises-Fisher distribution (a normal distribution on a unit sphere) and parametrised according to the directionality and degree of anisotropy in the diffusion tensors. We demonstrate the results in a simple model for glioma growth, exploiting both synthetic and genuine DTI datasets to reveal the potentially crucial role of anisotropic structure on invasion.

Atividade antimicrobiana de óleos essenciais no controle de alguns fitopatógenos fúngicos in vitro e no tratamento de sementes / Antimicrobial activity of essential oils on the in vitro control of some fungal phytopathogens and on seed treatment

Este trabalho verificou o efeito dos óleos essenciais (OE) extraídos de Eremanthus erythropappus (candeia), Cymbopogon martinii (palmarosa) e de Rosmarinus officinalis (alecrim) no crescimento micelial de alguns fitopatógenos fúngicos e no tratamento de sementes de milho, soja e feijão. No teste in vitro, alíquotas de 20, 40, 60, 100, 200, 500 e 1000 μL de cada um dos óleos essenciais foram distribuídas na superfície do meio de cultura. Posteriormente, discos de meio de cultura com micélio de Alternaria carthami, Alternaria sp. e Rhizoctonia solani foram transferidos para o centro de cada placa. O crescimento foi mensurado e calculada a taxa de inibição do crescimento micelial (ICM). Para verificar o efeito dos OE na germinação das sementes utilizou-se a aplicação deles por fumigação. Foi avaliada a percentagem de sementes germinadas e a incidência de patógenos nas sementes. Sobre o crescimento micelial, o óleo de palmarosa inibiu completamente todos os patógenos fúngicos, independentemente da concentração. Já os óleos de candeia e alecrim foram melhores quando foram adicionadas alíquotas superiores a 200 μL. Os óleos influenciaram diferentemente a germinação e a sanidade das sementes de milho, soja e feijão.

This study aimed to verify the effect of essential oils (EO) extracted from Eremanthus erythropappus ("candeia") Cymbopogon martinii ("palmarosa") and Rosmarinus officinalis (rosemary) on the mycelial growth of some fungal phytopathogens, as well as on the treatment of corn, soybean and bean seeds. In the in vitro test, aliquots of 20, 40, 60, 100, 200, 500 and 1000 μL of each essential oil were distributed on the surface of the culture medium. Then, discs of culture medium with mycelium of Alternaria carthami, Alternaria sp and Rhizoctonia solani were transferred to the center of each plate. Growth was measured and the mycelial growth inhibition rate (MGI) was calculated. To verify the effect of EO on seed germination, application of oils was by means of fumigation. Percentage of germinated seeds and their incidence of pathogens were evaluated. For mycelial growth, "palmarosa" oil completely inhibited all fungal pathogens, regardless of the concentration. On the other hand, "candeia" and rosemary oils were better when aliquots higher than 200 μL were added. The oils differently influenced the germination and health of corn, soybean and bean seeds.

Linear quadratic and tumour control probability modelling in external beam radiotherapy.

The standard linear-quadratic (LQ) survival model for external beam radiotherapy is reviewed with particular emphasis on studying how different schedules of radiation treatment planning may be affected by different tumour repopulation kinetics. The LQ model is further examined in the context of tumour control probability (TCP) models. The application of the Zaider and Minerbo non-Poissonian TCP model incorporating the effect of cellular repopulation is reviewed. In particular the recent development of a cell cycle model within the original Zaider and Minerbo TCP formalism is highlighted. Application of this TCP cell-cycle model in clinical treatment plans is explored and analysed.

A user's guide to PDE models for chemotaxis.

Mathematical modelling of chemotaxis (the movement of biological cells or organisms in response to chemical gradients) has developed into a large and diverse discipline, whose aspects include its mechanistic basis, the modelling of specific systems and the mathematical behaviour of the underlying equations. The Keller-Segel model of chemotaxis (Keller and Segel in J Theor Biol 26:399-415, 1970; 30:225-234, 1971) has provided a cornerstone for much of this work, its success being a consequence of its intuitive simplicity, analytical tractability and capacity to replicate key behaviour of chemotactic populations. One such property, the ability to display "auto-aggregation", has led to its prominence as a mechanism for self-organisation of biological systems. This phenomenon has been shown to lead to finite-time blow-up under certain formulations of the model, and a large body of work has been devoted to determining when blow-up occurs or whether globally existing solutions exist. In this paper, we explore in detail a number of variations of the original Keller-Segel model. We review their formulation from a biological perspective, contrast their patterning properties, summarise key results on their analytical properties and classify their solution form. We conclude with a brief discussion and expand on some of the outstanding issues revealed as a result of this work.

Pattern formation in prey-taxis systems.

In this paper, we consider spatial predator-prey models with diffusion and prey-taxis. We investigate necessary conditions for pattern formation using a variety of non-linear functional responses, linear and non-linear predator death terms, linear and non-linear prey-taxis sensitivities, and logistic growth or growth with an Allee effect for the prey. We identify combinations of the above non-linearities that lead to spatial pattern formation and we give numerical examples. It turns out that prey-taxis stabilizes the system and for large prey-taxis sensitivity we do not observe pattern formation. We also study and find necessary conditions for global stability for a type I functional response, logistic growth for the prey, non-linear predator death terms, and non-linear prey-taxis sensitivity.

Continuous traveling waves for prey-taxis.

Spatially moving predators are often considered for biological control of invasive species. The question arises as to whether introduced predators are able to stop an advancing pest or foreign population. In recent studies of reaction-diffusion models, it has been shown that the prey invasion can only be stopped if the prey dynamics observes an Allee effect. In this paper, we include prey-taxis into the model. Prey-taxis describe the active movement of predators to regions of high prey density. This effect leads to the observation that predators are drawn away from the leading edge of a prey invasion where its density is low. This leads to counterintuitive result that prey-taxis can actually reduce the likelihood of effective biocontrol.

Self ratings of health predict functional outcome and recurrence free survival after stroke.

STUDY OBJECTIVE: To measure stroke victims' self rated health (SRH) status and SRH transition, and to compare how the two are prospectively associated with disability and recurrence free survival. DESIGN: Prospective case registry study with face to face follow up interviews at three months, one, two, and three years. Ascertained were SRH status and SRH transition using single question assessments, Barthel Index (BI), Frenchay Activities Index (FAI), and Mini Mental State Examination (MMSE). SETTING: A multiethnic inner city population of 234 533. PARTICIPANTS: Patients surviving the initial three months after a first in a lifetime stroke in 1995 to 1998. RESULTS: Of 690 stroke survivors 561 (81.3%) could complete the self report items. Answers to the item on SRH status did not vary significantly between the four follow up interviews. However, responses to the item on SRH transition changed significantly during follow up with three months ratings being more negative than all subsequent ratings. SRH transition, but not SRH status, showed a prospective association with long term outcome in multivariate analyses controlling for the BI, FAI, and MMSE. Compared with all other patients, patients reporting "Much worse health" at three months were more likely to be disabled ( = BI<20) at one year (OR 6.29, 95% CI 2.26 to 17.52) and their combined risk of stroke recurrence and death was increased over five years (HR 1.72, 95% CI 1.25 to 2.38). CONCLUSIONS: Items on SRH should be used with caution in populations with high rates of disability and language problems, as many participants are unable to complete them. SRH transition may be a better predictor of disability and recurrence free survival after major medical events than SRH status.

Cattaneo models for chemosensitive movement: numerical solution and pattern formation.

We derive models for chemosensitive movement based on Cattaneo's law of heat propagation with finite speed. We apply the model to pattern formation as observed in experiments with Dictyostelium discoideum, with Salmonella typhimurium and with Escherichia coli. For Salmonella typhimurium we make predictions on pattern formation which can be tested in experiments. We discuss the relations of the Cattaneo models to classical models and we develop an effective numerical scheme.

Cattaneo models for chemosensitive movement. Numerical solution and pattern formation.

We derive models for chemosensitive movement based on Cattaneo's law of heat propagation with finite speed. We apply the model to pattern formation as observed in experiments with Dictyostelium discoideum, with Salmonella typhimurium and with Escherichia coli. For Salmonella typhimurium we make predictions on pattern formation which can be tested in experiments. We discuss the relations of the Cattaneo models to classical models and we develop an effective numerical scheme.

Incidence and case fatality rates of stroke subtypes in a multiethnic population: the South London Stroke Register.

OBJECTIVE: To identify sociodemographic differences in the incidence of the subtypes of first ever stroke in a multiethnic population. METHODS: A prospective community stroke register (1995-8) was developed using multiple notification sources and pathological and clinical classifications of stroke. Standardisation of rates was to European and World populations and adjusted for age, sex and socioeconomic status in multivariate analyses. A multiethnic population of 234 533 in south London, of whom 21% are black was studied. RESULTS: A total of 1254 cases were registered. The average age of stroke was 71.7 years with black patients being 11.3 years younger than white patients (p<0.0001). The incidence rate/1000 population was 1.33 (crude) (95% CI 1.26 to 1.41), 1.28 (European adjusted) (95% CI 1.2 to 1.35) with a 2.18 (95% CI 1.86 to 2.56) (p<0.0001) age and sex adjusted incidence rate ratio in the black population. Radiological diagnosis was confirmatory in 1107 (88.3%) with 862 (68.7%) infarction, 168 (13.4%) primary intracerebral haemorrhage, and 77 (6.2%) subarachnoid haemorrhage. Of the cerebral infarction cases 189 (21.9%) were total anterior circulatory, 250 (29%) partial anterior, 141 (16.4%) posterior (POCI) and 282 (32.7%) lacunar infarcts. The black group had a significantly higher incidence of all subtypes of stroke except for POCI and unclassified strokes. The incidence rate ratio (IRR) for men compared with women was 1.34 (95% confidence interval (95% CI) 1.19 to 1.50; p<0.001). The IRR for manual versus non-manual occupations in those aged 35-64 years was 1.64 (95%CI 1.22 to 2.23; p<0.0001). There was a borderline significant increase in adjusted survival at 6 months in the black group 95% (CI 0.61 to 1.03, p=0.078) with a hazard ratio of 0.79 after adjustment and stratification. CONCLUSIONS: Although the black population is at increased risk of stroke and most subtypes of stroke, this is not translated into significant differences in survival. Hence black/white differences in mortality are mainly driven by incidence of stroke. There are striking demographic inequalities in the risk of stroke in this multiethnic inner city population that need to be tackled through interagency working. Although the reasons for the increased risk in the black population are unclear, demographic factors such as socioeconomic status do seem to play a significant independent part.

Selective secretion of protein kinase C isozymes by thrombin-stimulated human platelets.

The protein kinase C (PKC) was secreted from thrombin-stimulated human platelets in a time- and dose-dependent manner. The PKC specific inhibitors Ro31-8220 (0.05 microM) and GF 109203X (0.5 microM) totally inhibited the secreted kinase activity. Western blot analysis of the secretory components showed reactivity to PKCalpha, PKCbetaII, and PKCdelta antibodies, but not to PKCbetaI, and p42/44 MAPK, although they were present in lysed platelets. The fractionation of platelets secreted components showed that PKC activity increased in both soluble and microparticle fractions after thrombin treatments. This is the first report demonstrating that activated human platelets selectively secrete protein kinase C isozymes. Protein kinase C secreted by platelets in this unique manner may have an extracellular role in the plasma, and may regulate cellular functions, including remodeling of vascular endothelial cells.