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Plasma norepinephrine samples were obtained before and after exposure to auditory stimuli reminiscent of combat from two groups of male Vietnam veterans with combat experience: one with diagnoses of PTSD (N = 15) and one with no mental disorder (N = 6). Results showed a significant 30% rise in plasma norepinephrine for the PTSD group, with no change in the comparison group.

When the Advisory Committee on Immunization Practices added the sequential schedule to the poliovirus vaccine (PW) recommendations in 1997, primary care physicians expressed concern about its implementation. This study examines the practices and factors influencing the administration of sequential, oral, or inactivated PW schedules by family physicians and pediatricians.A random sample of Ohio family physicians and pediatricians was surveyed between January and April 1998. Primary outcome measures included physicians' awareness of the 1997 recommendations, their recommendations to parents and caregivers, administration of current PW options, and the factors influencing their practices.All physicians who immunize children (n = 263) reported awareness of the 1997 PW recommendations. Family physicians were more likely to recommend and administer oral polio vaccine than pediatricians (50% and 63% vs 17% and 28%; P.001). Pediatricians were more likely to recommend and administer the sequential schedule than family physicians (66% and 67% vs 31% and 28%; P.001). Choice of sequential schedule was related to the risk of vaccine-associated paralytic poliomyelitis and liability (Por = .05). Choice of an all oral polio vaccine schedule was related to cost of inactivated PW and increased number of injections (Por = .05). One hundred eighty-two physicians (69%) indicated that they personally discuss PW options with parents or caregivers; only 41% have them read the required vaccine information sheets.Differences exist between family physicians' and pediatricians' implementation of the 1997 PW recommendations. Physician choice of PW schedule is influenced by the risk of vaccine-associated paralytic poliomyelitis, increased number of injections, liability concerns, and vaccine cost. Physicians need to inform parents of vaccine benefits and risks to comply with federal regulations.

To determine whether mammary gland or colostral characteristics at calving could be used to predict colostral immunoglobulin G1 (IgG1) concentration or intramammary infection (IMI) and whether leakage of colostrum affects IgG1 concentration.Prospective study.113 multiparous Holstein cows.Cows were examined within 3 hours of calving, and mammary gland and colostral characteristics, colostral volume, somatic cell count, and concentrations of IgG1, fat, and protein were determined. Bacteriologic culture of mammary secretions was performed approximately 14 and 7 days before calving and at calving. Associations of gland and colostral characteristics with colostral IgG1 concentration, colostral volume, and IMI were examined.Thick or thin colostrum had higher IgG1 concentration than colostrum of intermediate viscosity. Colostrum from mammary glands that were firm had low IgG1 concentration. Colostral IgG1 concentration was weakly correlated with volume. Intramammary infection was likely to be detected if colostrum contained clots or blood or if the California Mastitis Test (CMT) score wasor = 2. Somatic cell count was higher for glands with IMI than for uninfected glands, and CMT score was correlated with cell count.Mammary gland and colostral characteristics were of little value in predicting IgG1 concentration. Our findings do not support recommendations that first milking colostrum that is thin (watery) or that is from cows producing large volumes not be fed to dairy calves. Colostral characteristics, particularly CMT score, were of value for predicting IMI.

This report describes a case of apparent confined placental mosaicism for trisomy 8 in a pregnancy which produced a male infant with intra-uterine growth retardation. Postnatal cytogenetic and molecular studies were consistent with biparental disomy 8. Postnatally, the infant experienced a period of rapid catch-up growth and exhibited no clinical features of trisomy 8 mosaicism. His development was age appropriate.

Hypotony from an inadvertent filtration bleb developed in the eye of a 66-year-old woman 1 year after phacoemulsification cataract surgery. The hypotony was treated with an autologous blood injection over the previous phacoemulsification incision. This technique successfully treated the hypotony without additional ocular surgery. The authors report an effective alternative treatment for hypotony induced by an inadvertent filtration bleb.

To determine whether antibiotic and supportive treatment would improve outcome for dairy cows with naturally developing clinical mastitis, compared with supportive treatment alone.Randomized controlled trial.124 cows in one herd with 172 episodes of clinical mastitis.Cows were examined at the onset of clinical mastitis, assigned a severity score, and randomly assigned to receive antibiotic (intramammary administration of cephapirin, i.v. administration of oxytetracycline, or both) and supportive treatment (administration of oxytocin, stripping of affected glands, and, in severely affected cows, administration of flunixin meglumine or fluids) or supportive treatment alone. Treatment was continued until 24 hours after signs of clinical mastitis resolved (clinical cure). Milk samples from affected glands were submitted for bacterial culture before initial treatment and every 2 weeks thereafter until the causative organism was no longer isolated (bacteriologic cure).When mastitis was caused by Streptococcus spp or coliform bacteria, clinical cure rate by the tenth milking was significantly higher if antibiotics were used. Bacteriologic cure rate at 14 days was significantly higher when antibiotics were used, particularly if mastitis was caused by Streptococcus spp. Cows receiving antibiotics developed fewer subsequent episodes of clinical mastitis during the 60 days after the initial episode of mastitis and had less severe clinical disease than cows that did not.Results suggest that, in herds in which mastitis is often caused by environmental bacteria, antibiotic and supportive treatment may result in a better outcome for cows with clinical mastitis than supportive treatment alone.

To determine whether clinical parameters could be used to differentiate clinical mastitis (CM) caused by gram-positive bacteria from CM caused by gram-negative bacteria in dairy cows vaccinated against lipopolysaccharide core antigens.Case series.143 episodes of CM in 86 dairy cows in a single herd.Cows were examined at onset of CM, and 24 clinical parameters including rectal temperature, heart rate, rumen contraction rate, degree of dehydration, various udder and milk characteristics, lactation number, stage of lactation, and season of year were recorded. Milk production and milk constituent concentrations before onset of CM were obtained from Dairy Herd Improvement Association records. Values for cows with gram-negative CM were compared with values for cows with gram-positive CM. Logistic regression was used to identify important predictors of gram-negative CM.64 (45%) CM episodes were caused by gram-negative bacteria and 79 (55%) were caused by gram-positive bacteria. Rumen contraction rate was significantly lower and milk protein percentage before onset of CM was significantly higher in cows with gram-negative, rather than gram-positive, CM. Logistic regression indicated that CM was more likely to have been caused by gram-negative bacteria if it developed during the summer, milk was watery, or rumen contraction rate was low. Sensitivity and specificity of the final regression model were 0.58 and 0.80, respectively. Predictive value of a positive result was 0.74 when proportion of CM episodes caused by gram-negative bacteria was assumed to be 50%.Results suggest that clinical observations do not allow accurate prediction of CM pathogens and should not be the sole criteria for deciding whether cows with CM are treated with antibiotics.

Background: The decision to recommend removal or conservation of a normal ovary and uterus in a young woman with advanced ovarian cancer is difficult and controversial. Case: A 21-year-old patient with a large-cell variant of small-cell carcinoma of the ovary stage IIIc underwent optimal debulking surgery with preservation of the normal appearing uterus and opposite adnexa followed by aggressive multi-agent chemotherapy. She is menstruating normally and is free of disease, more than 2 years since completion of chemotherapy. Conclusion: In selected cases, conservation of the uninvolved ovary and uterus in patients with advanced-stage, small-cell carcinoma of the ovary may not compromise survival.

The endovaginal probe can be used in the umbilicus to improve fetal imaging. In 27 of 31 patients, an optimal ultrasound examination was achieved because of this added technique. The procedure is most useful in obese women and those with prior abdominal surgery.

Lupus, one of the most common autoimmune diseases in pregnancy, may involve multiple organ systems with varying severity. The diagnosis and treatment of the disease may be complicated by the physiologic changes of pregnancy.A 22-year-old woman presented at 29 weeks' gestation with a 4-week history of dyspnea and mild hypertension. She was found to have large bilateral pleural effusions. Her antinuclear antibody level was 1:640, with a speckled pattern, and her complement levels were low. Her urine had 2+ hemoglobin and 2+ protein with hyaline casts. Over the next three days, respiratory compromise increased despite high-dose steroids. A cesarean delivery was performed for fetal compromise. The infant did well after moderate respiratory distress. The mother developed worsening respiratory distress with adult respiratory distress syndrome, and she could not be weaned from the ventilator. Bilateral chest tubes were placed to control her effusions. Urine output remained poor despite pressors and diuretics. Staphylococcal sepsis occurred on postoperative day 5 and precluded our use of other antiinflammatory agents. Over the next 14 days the mother developed seizures, hypotension and eventual respiratory collapse. Autopsy was notable for lupus nephritis and serositis.The diagnosis and management of systemic lupus in pregnancy may be extremely difficult. Serositis and nephritis may lead to maternal compromise despite early diagnosis and treatment.

Fetal and neonatal ovarian cysts can be small asymptomatic lucencies or large symptomatic echocomplex masses that can cause intestinal obstruction and peritonitis. Solid masses are the most rare form of ovarian cysts. A fetus, anatomically unremarkable at 16 weeks' development, was found at 35 weeks to have a 5 x 5 cm solid mass. After delivery a laparotomy was performed, and a torsed ovary measuring 8 x 7 cm was removed. The infant did well after the procedure. Over 400 cases of perinatal ovarian cysts have been reported in the literature. Only 1% of these are purely echodense. When a fetal abdominal mass is present, separate from bowels and kidneys, a torsed ovary should be considered in the differential diagnosis. Management of the pregnancy and infant may be guided by the fetus or neonate's symptoms.

[McCoy M: Domestic violence: Clues to victimization. Ann Emerg Med June 1996;27:764-765.]

Radioisotope Thermoelectric Generators (RTG) convert the heat generated by radioactive decay to electricity using thermocouples. RTGs have a long operating life, are reasonably lightweight, and require little or no maintenance once assembled and tested. These factors make RTGs particularly attractive for use in spacecraft. However, because RTGs contain significant quantities of radioactive materials, normally plutonium‐238 and its decay products, they must be transported in packages built in accordance with Title 10, Code of Federal Regulations, Part 71. The U.S. Department of Energy assigned the Radioisotope Thermoelectric Generator Transportation System (RTGTS) Program to Westinghouse Hanford Company in 1988 to develop a system meeting the regulatory requirements. The program objective was to develop a transportation system that would fully comply with 10 CFR 71 while protecting RTGs from adverse environmental conditions during normal conditions of transport (e.g., shock and heat). The RTGTS is scheduled for completion in December 1996 and will be available to support the National Aeronautics and Space Administration’s Cassini mission to Saturn in October 1997. This paper provides an overview of the RTGTS and discusses the hardware being produced. Additionally, various program management innovations mandated by recent major changes in the U.S. Department of Energy structure and resources will be outlined.

The cult of Elizabeth has traditionally been seen as a propaganda triumph for Tudor despotism, flourishing paradoxically in the final decade of her reign when the queen's difficulties and decline had to be concealed beneath what Roy Strong calls ‘the mask of youth’. In his influential study of her cult and the artwork and pageantry that it inspired, Strong argues that ‘the mask of youth’ worked as long as her courtiers ‘could yet join in paeans to the Divine One who alone seemed capable of holding together the world they knew’. The fair complexion and the blush of youth were, of course, a facade sustained by make-up and make-believe, but still the tributes continued to her virtue and her beauty. Midway through her reign, in the ‘Aprill’ eclogue of The Shepheardes Calendar (1579), Edmund Spenser had blended the tropes of Petrarchan compliment with the heraldic devices of the Tudor dynasty in his portrait of Elizabeth: Tell me, have ye seene her angelick face. Like Phoebe fayre? Her heavenly haveour, her princely grace Can you well compare? The Redde rose medled with the White yfere, In either cheeke depeincten lively chere. Twenty years later those roses still flourished in both the paintings and poetry of her last decade. Sir John Davies dedicates his most ambitious work, Nosce Teipsum (1599) to Elizabeth: Faire Soule , since to the fairest bodie knit, You give such lively life, such quickning power, Such sweete, celestiall influence to it, As keepes it still in youths immortall flower.

It is proposed that clinicians screen all pregnant women at high risk for preterm labor and premature rupture of membranes for bacterial vaginosis, and treat all women when it is diagnosed. This infection is associated with a two to three times increase in preterm labor and delivery, premature rupture of the membranes, and endometritis. Although cause and effect have not been conclusively documented, these associations must be considered in the practice of obstetrics at the present. The paucity of vaginal Lactobacillus spp is pivotal in allowing overgrowth of many other organisms of the vagina. Screening is suggested because 50 percent of bacterial vaginosis is asymptomatic. The diagnosis, which is rapidly made and inexpensive, remains defined by clue cells seen on wet prep, high vaginal pH, and amine odor of the vaginal discharge. Optimal treatment of pregnant women with bacterial vaginosis is via oral or intravaginal metronidazole or clindamycin.

Background : Uterine torsion is defined as the rotation of more than 45° around the long axis of the uterus. An uncommon but potentially fatal event, uterine torsion is rarely diagnosed until the time of surgery. With magnetic resonance imaging (MRI), however, an accurate diagnosis of uterine torsion may now be made preoperatively. Case : We describe a patient with uterine torsion in whom the correct diagnosis was made prenatally with the use of MRI, by the demonstration of an X-shaped configuration of the upper vagina. Conclusion : Distinctive features suggestive of uterine torsion were demonstrated by MRI and enabled an accurate preoperative diagnosis. To our knowledge, this is the first reported case of uterine torsion diagnosed on MRI.

Data from morphology, linguistics, history, and archaeology have all been used to trace the dispersal of chickens from Asian domestication centers to their current global distribution. Each provides a unique perspective which can aid in the reconstruction of prehistory. This study expands on previous investigations by adding a temporal component from ancient DNA and, in some cases, direct dating of bones of individual chickens from a variety of sites in Europe, the Pacific, and the Americas. The results from the ancient DNA analyses of forty-eight archaeologically derived chicken bones provide support for archaeological hypotheses about the prehistoric human transport of chickens. Haplogroup E mtDNA signatures have been amplified from directly dated samples originating in Europe at 1000 B.P. and in the Pacific at 3000 B.P. indicating multiple prehistoric dispersals from a single Asian centre. These two dispersal pathways converged in the Americas where chickens were introduced both by Polynesians and later by Europeans. The results of this study also highlight the inappropriate application of the small stretch of D-loop, traditionally amplified for use in phylogenetic studies, to understanding discrete episodes of chicken translocation in the past. The results of this study lead to the proposal of four hypotheses which will require further scrutiny and rigorous future testing, Excavations in Fais by MI were made possible by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science. DB gratefully acknowledges support from the Marsden Fund, and the Allan Wilson Centre for Molecular Ecology and Evolution. During the course of this research AS was supported by a Postgraduate Scholarship from the University of Auckland and a Fellowship from the Allan Wilson Centre for Molecular Ecology and Evolution

Diclofenac is a nonsteroidal anti-inflammatory agent that is reported to cause serious hepatic injury in some patients. To investigate the possibility that protein adducts derived from reactive intermediates of diclofenac might be responsible for the hepatotoxicity produced by this drug, we recently developed polyclonal antisera that recognized protein adducts of diclofenac. In the present study, we have characterized further the diclofenac adducts in rat liver. Immunoblotting studies showed that diclofenac-labeled hepatic proteins were formed in a dose- and time-dependent manner in rats given diclofenac. Subcellular fractionation of liver homogenates from diclofenac-treated rats showed that a 50-kDa microsomal protein and 110-, 140-, and 200-kDa plasma membrane proteins were labeled preferentially. Immunofluorescence studies of isolated hepatocytes and immunohistochemical analysis of liver slices from diclofenac-treated mice and rats confirmed that plasma membrane proteins were labeled by diclofenac metabolites and showed that the bile canalicular domain of the plasma membrane was a major site of diclofenac adduct formation. Additionally, we found that cytochrome P-450 and UDP-glucuronosyltransferase, but not acyl-CoA synthase, catalyzed the formation of reactive intermediates of diclofenac that were bound covalently to proteins in vitro. The metabolites catalyzed by cytochrome P-450 in vitro were bound exclusively to a 50-kDa microsomal protein, even in the presence of albumin. In contrast, the 110-, 140-, and 200-kDa plasma membrane proteins as well as others appeared to be labeled when diclofenac was activated by UDP-glucuronosyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

Introduction -Clark Hulse and Peter Erickson 1. Imaginary Conquests: European Material Technologies and the Colonial Mirror Stage -Steven Mullaney 2. Mapping the Global Body -Valerie Traub 3. Second-World Prosthetics: Supplying Deficiencies of Nature in Renaissance Italy -Harry Berger, Jr. 4. Reading Painting: Holbein, Cromwell, Wyatt -Clark Hulse 5. Art for the Sake of Dynasty: The Black Emperor in the Drake Jewel and Elizabethan Imperial Imagery -Karen C. C. Dalton 6. Staging Women's Relations to Textiles in Shakespeare's Othello and Cymbeline -Susan Frye 7. Idols of the Gallery: Becoming a Connoisseur in Renaissance England -Stephen Orgel 8. Madagascar on My Mind: The Earl of Arundel and the Arts of Colonization -Ernest B. Gilman 9. "God for Harry, England, and Saint George": British National Identity and the Emergence of White Self-Fashioning -Peter Erickson 10. Object into Object? Some Thoughts on the Presence of Black Women in Early Modern Europe -Kim F. Hall Epilogue -Peter Erickson Contributors: Harry Berger Jr. (University of California, Santa Cruz) has recently published three books: Revisionary Play: Studies in the Spenserian Dynamic, Imaginary Audition: Shakespeare on Stage and Page, and Making Trifles of Terrors: Redistributing Complicities in Shakespeare. His new book is Fictions of the Pose: Rembrandt Against the Italian Renaissance. Karen C. C. Dalton (Harvard University) is coauthor of Winslow Homer's Images of Blacks: The Civil War and Reconstruction Years and editor of the final three volumes of The Image of the Black in Western Art, covering the sixteenth through eighteenth centuries. Peter Erickson (Sterling and Francine Clark Art Institute) is author of Patriarchal Structures in Shakespeare's Drama and Rewriting Shakespeare, Rewriting Ourselves, and coeditor of Shakespeare's "Rough Magic": Renaissance Essays in Honor of C. L. Barber. Susan Frye (University of Wyoming) has written Elizabeth I: The Competition for Representation and coedited Maids and Mistresses, Cousins and Queens: Women's Alliances in Early Modern England. Ernest B. Gilman (New York University) is author of Iconoclasm and Poetry in the English Reformation: Down Went Dagon and The Curious Perspective: Literary and Pictorial Wit in the Seventeenth Century. Kim F. Hall (Georgetown University) has written Things of Darkness: Economies of Race and Gender in Early Modern England as well as essays on teaching the subject of race in Shakespeare's plays. Clark Hulse (University of Illinois at Chicago), is author of The Rule of Art: Literature and Painting in the Renaissance and Metamorphic Verse: The Elizabethan Minor Epic. He is currently working on a study of Holbein and the age of Henry VIII. Steven Mullaney (University of Michigan) has written The Place of the Stage: License, Play, and Power in Renaissance England. He is at work on two books, Mourning and Misogyny: Reformation of Affect and Ideology in Shakespeare's England, and Emotions and Its Discontents. Stephen Orgel (Stanford University) has recently published Impersonations: The Performance of Gender in Shakespeare's England and Oxford editions of The Tempest and The Winter's Tale. Valerie Traub (University of Michigan) is author of Desire and Anxiety: Circulations of Sexuality in Shakspearean Drama and coeditor of Feminist Readings of Early Modern Culture: Emerging Subjects.

Transfusion-associated graft-versus-host disease (TA-GVHD) may occur whenever immunologically competent allogeneic lymphocytes are transfused to an immunocompromised recipient. Irradiation of blood components eliminates the risk of TA-GVHD but may damage the cellular elements in the transfused component, particularly if the cells are stored for prolonged periods in the irradiated state. To study the effect of irradiation on long-term storage of red cells, AS-1 red cells from eight normal subjects were prepared on two occasions. On one occasion, the units were stored as standard AS-1 red cells for 42 days at 4 degrees C; on the other, they were exposed to 3000 cGy radiation within 4 hours of collection and then were stored as AS-1 red cells for 42 days at 4 degrees C. The donations were at least 12 weeks apart. Irradiated units demonstrated significant elevations in poststorage plasma hemoglobin (Hb) (623 +/- 206 vs. 429 +/- 194 g/dL [6230 +/- 2060 vs. 4290 +/- 1940 g/L], p less than 0.02) and plasma potassium (78 +/- 4 vs. 43 +/- 9 mEq/L [78 +/- 4 vs. 43 +/- 9 mmol/L], p less than 0.01) and significant decreases in red cell ATP (1.9 +/- 0.2 vs. 2.1 +/- 0.3 microM/g Hb, p less than 0.04) and 24-hour posttransfusion red cell recovery (68.5 vs. 78.4%, p less than 0.02), as compared to nonirradiated units. It can be concluded that irradiation with 3000 cGy damages red cells and that long-term storage in the irradiated state may enhance this damage. Red cells should not be stored for 42 days after irradiation with 3000 cGy.

The development and implementation of process, structure, and outcome standards were an integral part of program development for a mobile mammography screening program that provides service for the economically disadvantaged through the collaborative effort of eight primary healthcare centers, the Dade County Health Department, and the University of Miami/Jackson Memorial Hospital. The standards are used to guide and evaluate the screening program's operation and to provide the framework for additional program components (e.g., developing performance appraisals and quality assurance and risk management programs, establishing policies and procedures, and serving as the foundation for education and research projects). Examples of standards are provided to assist others in developing a systematic and ongoing evaluation plan for mobile mammography screening.

Ten male hypertensives, whose BPs were controlled on a combination of sympatholytic and diuretic medications, were given 16 sessions of thermal biofeedback prior to attempting withdrawal from the sympatholytic drug. Results were evaluated using 24-hr ambulatory BP monitoring (ABPM) as well as clinic and home BPs, both in multi-baseline-across-subject designs and as a single group. Results showed significant treatment effects on 24-hr ABPM data, both at the individual level (SBPs only) and in the aggregate analyses (SBP and DBP). BPs assessed in the clinic by random zero sphygmomanometer and patient-assessed home BPs were also reduced.

2073 Background: ZK304709 is a novel MTGI that selectively inhibits activity of Cyclin Dependent Kinases (CDKs) 1, 2, 4, 7, 9, and the tyrosine kinase activity of VEGF-R 1, 2, 3 and PDGF-βR. Methods: Adult patients (pts) with a good performance status (WHO PS ≤2) and a histologically or cytologically confirmed relapsed/refractory solid tumor were eligible. ZK304709 is administered, as a monotherapy, orally on days 1–7 of a 21-day cycle to fasting patients at a starting dose of 15 mg qd. Dose escalation has ranged from 33% - 100% of prior dose, depending on occurrence of drug-related toxicity ≥ grade (gr) 2 (CTC v2.0). Between 3 and 7 patients are to be enrolled per dose level, depending on DLTs that are observed. The primary objective is determination of the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of ZK304709. Secondary objectives include tolerability, pharmacokinetic (PK) profile, and preliminary efficacy. Results: Interim results are available for 22 pts (15 M/7 F, median age 60.5 yrs; range 37–71) treated with ZK304709 at 6 dose levels (15 - 180 mg qd). Patients completed a median of 2 cycles (range 0–8). Common AEs were nausea, vomiting, diarrhea, and lethargy. Two DLT were observed: supraventricular tachycardia and vomiting, but the MTD was not reached. The PK profile shows rapid absorption, with a Tmax of 2–4 hrs, and a dose-dependent increase in systemic exposure over the 15–90 mg dose range. Disease stabilization for ≥4 cycles has been observed. Conclusions: ZK304709 is rapidly absorbed and has been tolerated on this schedule at doses up to 180 mg qd. The MTD has not been reached, and enrolment is ongoing. These preliminary data demonstrate that oral delivery on this schedule of an agent that inhibits both cell cycle and angiogenesis is feasible. [Table: see text]

2076 Background: ZK 304709 is a novel oral MTGI that induces cell cycle arrest and inhibits tumour angiogenesis by selectively inhibiting Cyclin Dependent Kinases (CDKs) 1, 2, 4, 7 and 9,VEGF-R 1, 2 and 3, and PDGF-Rβ tyrosine kinases. Methods: Adult patients (pts) (WHO PS ≤2) with a histologically or cytologically confirmed solid tumor, resistant or refractory to conventional therapy, were eligible. ZK304709 was administered orally, once daily, at a 15 mg starting dose, on days 1–14 of a 28-day cycle, then escalated by 33–100% depending on incidence of drug-related toxicity ≥ grade (gr) 2 (CTC v2.0). At least 3 pts were treated at each dose level. The primary objective was to identify the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT). Secondary objectives were to determine the tolerability, pharmacokinetic (PK) profile, and preliminary efficacy. Results: Interim results were available for 24 pts (19 M/5 F; median age 56.5) at 5 dose levels (15–120 mg qd). Pts received a median of 2 cycles (range 0–10). Common drug related toxicities were nausea, vomiting, and fatigue. Two DLT were observed: dizziness and hypertension. However, the MTD has yet to be established. The PK profile for dose levels up to 90 mg demonstrated rapid absorption and a dose-dependent increase of exposure and Cmax. Disease stabilization for ≥4 cycles has been observed. Conclusions: ZK 304709 was rapidly absorbed and has been tolerated on this schedule at up to 120 mg qd. The MTD has not been reached and enrolment is ongoing. These preliminary data demonstrate that oral delivery on this schedule of an agent that inhibits both cell cycle and angiogenesis is feasible. [Table: see text]

3026 Background: Inhibition of HDACs in vitro has resulted in tumor cell growth arrest, differentiation and/or tumor apoptosis. This report evaluates the pharmacokinetics (PK) and pharmacodynamics ...