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PURPOSE The Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) requires eligible clinicians to report clinical quality measures (CQMs) in the Merit-Based Incentive Payment System (MIPS) to maximize reimbursement. To determine whether structured data in electronic health records (EHRs) were adequate to report MIPS CQMs, EHR data aggregated by ASCO's CancerLinQ platform were analyzed. MATERIALS AND METHODS Using the CancerLinQ health technology platform, 19 Oncology MIPS (oMIPS) CQMs were evaluated to determine the presence of data elements (DEs) necessary to satisfy each CQM and the DE percent population with patient data (fill rates). At the time of this analysis, the CancerLinQ network comprised 63 active practices, representing eight different EHR vendors and containing records for more than 1.63 million unique patients with one or more malignant neoplasms (1.73 million cancer cases). RESULTS Fill rates for the 63 oMIPS-associated DEs varied widely among the practices. The average site had at least one filled DE for 52% of the DEs. Only 35% of the DEs were populated for at least one patient record in 95% of the practices. However, the average DE fill rate of all practices was 23%. No data were found at any practice for 22% of the DEs. Since any oMIPS CQM with an unpopulated DE component resulted in an inability to compute the measure, only two (10.5%) of the 19 oMIPS CQMs were computable for more than 1% of the patients. CONCLUSION Although EHR systems had relatively high DE fill rates for some DEs, underfilling and inconsistency of DEs in EHRs render automated oncology MIPS CQM calculations impractical.

175 Background: Abiraterone(A) and enzalutamide(E), both oral androgen receptor targeted agents, are available as first-line treatment options for mCRPC patients. Direct comparisons of efficacy have not been performed for mCRPC patients primarily receiving their cancer care outside of academic centers or integrated health care systems. The study aims to evaluate the real-world effectiveness between first-line A and E-containing regimens in mCRPC patients primarily receiving care in the US community oncology setting. Methods: Patients were selected from ConcertAI Patient 360 Prostate data product, a large de-identified database of deeply curated EHR RWD, sourced from data sharing agreements with community oncology practices. mCRPC patients treated with a first-line A or E-cont. regimen between 1/2011 and 6/2022 were included. OS, TTNT, TTD outcomes were described using KM estimates and evaluated with Cox proportional hazard (HR) model. Confounding was addressed with inverse probability treatment weighting (IPTW) propensity scores based on age, BMI, ECOG, prior anti-androgen exposure, smoking status, comorbidities, and nadir PSA. Sensitivity analysis evaluated KM and HR for each covariate strata. Hazard ratios were also evaluated with multiple imputation by chained equations for missing covariates. Results: From 3,578 mCRPC patients, 1,210 (33.8%) received E-cont. regimen and 1,357 (37.9%) received A-cont. regimen(ref) with a median of 8 months duration for both drugs. Adjusted HR (aHR) for all three outcomes showed a slight increase in effectiveness for E albeit not significant (OS (aHR 0.99, CI 0.87-1.12), TTNT (aHR 0.98, CI 0.89-1.08). Adjusted model including imputation (iHR) supported unimputed results (OS (iHR 0.97, CI 0.88-1.07), TTNT (aHR 0.94, CI 0.9-1.10). The HRs for OS, TTNT and TTD in sicker patients were consistent (2+ ECOG TTNT (aHR 0.95, 0.81-1.12)), (BMI >30, TTNT (aHR 0.84, 0.61-1.18)), and reached significance for some models (2+ ECOG TTD (aHR 0.66, 0.48-0.91)). Conclusions: First-line E-cont. regimens consistently showed increased effectiveness in outcomes compared to A-cont. regimens in mCRPC patients treated in community oncology setting. The effects sizes are modest and did not reach significance, however analysis of the sickest patients showed a trend of consistently larger effect sizes which reached significance for some outcomes. More work needs to be done to evaluate if these results support findings from other RWD sources.

e18074 Background: Physician reimbursement for care delivered to Medicare beneficiaries fundamentally changed with the 2015 MACRA legislation, requiring eligible clinicians to report quality measures in the Merit-Based Incentive Payment System (MIPS). To determine whether structured data in electronic health records (EHRs) were adequate to report MIPS results, EHR data ingested by ASCO’s CancerLinQ (CLQ) was analyzed. Methods: Nineteen MIPS measures specified for medical oncology, including 8 shared by other specialties, were retrieved from qpp.cms.gov and systematically evaluated to determine data elements necessary to satisfy each measure. The existence of corresponding data fields and completion of these fields with clinical data was analyzed according to EHR implementation in de-identified and aggregated CLQ data. Results: Five clinician informaticists reviewed the 19 oncology MIPS measures, and identified a consensus list of 52 discrete EHR data elements (DEs) that would be needed. CLQ-processed data from 4 commercial EHR systems implemented at 47 CLQ practices found structured data fields for 84% (43 of 52) of the DE, but fewer than half (46%) of these fields were ever populated and only 32% (17 of 52) of DE were recorded for > 20% of cases. Only 3-5 of 19 MIPS measures could be reliably reported based on data element availability by most practices in this sample set. There were minimal differences between the EHRs ability to encode MIPS DE. Elements most likely to be encoded were those for registration (birthdate, gender), billing (diagnosis, meds), vital signs and smoking status, while those seldom or never encoded related to care plans (tobacco, alcohol, pain management). Other DE rarely encoded were patient events occurring outside the oncology practice (receipt/completion of consultations, dates of hospice enrollment and death), which would be dependent on data exchange between work units and practice entities or, more likely, re-entry by oncology practices. Conclusions: Only a minority of DE required to satisfy MIPS criteria are available as discrete data fields in current EHRs, limiting automated reporting efforts. Improved data quality and completeness is needed to satisfy mandated reporting.

The journey from initial detection of malignancy to treatment plan for a new oncology patient is perilous at best. Clinicians are required to collate data from several disparate sources before treatment can be established; the time required is stressfulforthepatient,andthehandlingof patient data multiple times can lead to

10101Background: Cancer survivorship care planning was recognized as critical in a seminal 2005 Institute of Medicine report, From Cancer Patient to Cancer Survivor. Recently, the Commission on Can...

The acoustical efficiency of machines varies in the range of 10−9 to 10−5. This means even high power machines generate sound powers of a few Watts only. Due to the high sensitivity of the human ear however, such low sound powers create close to the machine loudnesses higher than 100 phon (64 sone). Consequently, the assessment of machinery noise emission requires relations to these subjective properties.

Summary The authors studied the combination of Kathon(R) CG and Germall(R) II (0.1%-0.1%) in hydrophilic creams. Their objective was to find an alternative to the use of parabens. Kathon(R) CG was chosen due to its antimicrobial effectiveness and its broad spectrum of activity. It must be indicated, however, that it has only a weak action against Staphylococcus aureus. In order to reinforce its microbicidal action it was combined with Germall(R) II. The Kathon(R) CG-Germall(R) II combination showed addition, indeed even synergy, with respect to Escherichia coli (Gram negative rod) and Aspergillus niger (fungus). In the case of Candida albicans (yeast) the antifungal effect of Kathon(R) CG dominates. Finally, the combination can have effects from addition to antagonism in the case of the three strains of Staphylococcus aureus tested (Gram positive coccus). The time required to eliminate 10(6) UFC of these bacteria per g of cream can often exceed 48 h. If the concentration of Germall(R) II is increased to 0.3% then the effectiveness of the mixture is markedly reinforced. Caution must be observed, however, due to recent apprehensions expressed by certain dermatologists concerning possible allergic reactions due to Kathon(R) CG. A multi-centre patch test study is currently being carried out with this preservative in the dermatological clinics of the five Swiss university hospitals.

Many timber trestle railroad bridges in Wisconsin have experienced deterioration and are in need of rehabilitation. In addition, the railroad industry is increasing the weights of cars. The combined effect of heavier loads and deterioration threatens to cut short the service life of timber bridges. One of the most critical problems that has been identified was the overloading of timber piles in bridges, which can be remedied by creating a stiffer pile cap. The goal of this investigation was to show that fiber reinforced polymer (FRP) strips fastened to timber with screws can be used to create composite action between two beams in flexure or truss action between two deep beams. Ultimately this may help redistribute the loads to piles when FRP strips are used as struts on cap beams over short spans. Several test series were conducted with beams in flexure, deep beams over short spans, and full scale specimens to determine the manner in which FRP strips improved the members’ performance. Mechanically fastened FRP strips were effective in developing composite action in slender beams in flexure and truss action in short deep beams.

Summary points Breast disorders in males can be distressing for both patients and examining doctors. Patients often feel embarrassed and anxious. Although cancers are diagnosed in only about 1% of cases of male breast enlargement, practitioners may feel uncertain about how to differentiate gynaecomastia (benign breast enlargement) from malignancy and how to manage these disorders. This review covers the causes, evaluation, and treatment of gynaecomastia and the risk factors for and evaluation and treatment of breast cancer in males. #### Sources and selection criteria We searched Medline for English language papers with the key words “gynaecomastia”, “gynecomastia”, and “male breast cancer”; the Cochrane database for clinical trials; our personal archives of references; and websites with those terms. We also referred to our institutional experience with gynaecomastia and male breast cancer. Gynaecomastia is the benign enlargement of male breast tissue (>2 cm palpable, firm, subareolar gland and ductal tissue) resulting from a relative decrease in androgen effect or increase in oestrogen effect. Breast enlargement due to adipose tissue is called pseudogynaecomastia. Male breast tissue contains receptors for androgen, oestrogen, and progesterone. Oestrogen stimulates duct development and progesterone stimulates alveolar development in the presence of the …

A comparison is made of Miami Indian death customs of the eighteenth and nineteenth centuries as described by French explorers ca. 1702 and by C. C. Trowbridge to Michigan Territorial Governer Lewis Cass in 1825. Changes in customs reflect the influence of time, invasion, and tribal identity on a universal observance. Distinguishing features of nineteenth century customs are the ceremonial provision of a surrogate to replace the deceased and protection of the corpse from an inimical medicine man. Similarities and differences between the death customs of the Miamis and other Great Lakes tribes are also noted.

e12029 Background: There is increasing evidence that platinum-based chemotherapy (PBC) is beneficial in breast cancer. Utilization of platinum agents are on the rise in potentially curable HER2-neg...

Der akustische Wirkungsgrad gerauscherzeugender Maschinen liegt im Allgemeinen in der Grosenordnung von 10−9 bis 10−5. Selbst sehr leistungsstarke Maschinen erzeugen damit haufig nur Schallleistungen von einigen Watt. Schallleistungen von wenigen Watt fuhren aber in Maschinennahe bereits zu unertraglichen Lautstarken von uber 100 phon. Die objektive Beurteilung der Larmerzeugung von Maschinen (Gerauschemission) ist deshalb auf Gerauschgrosen ausgerichtet, die auch bei der Beurteilung der Larmempfindung des Menschen (Gerauschimmission) Verwendung finden (vgl. Kap. 5).

246 Background: Albumin-bound paclitaxel is FDA approved as single agent for breast cancer, in combination with carboplatin for non-small cell lung cancer (NSCLC), and with gemcitabine for pancreatic cancer. Oncology Analytics (OA) is a cancer care decision support group comprised of board-certified oncologists, interacting with more than 2,800 cancer doctors in the Southeastern U.S. We have been making oncologists aware of comparative efficacy data, and the relative values of albumin-bound paclitaxel vs other taxanes. We hypothesized our work has impacted albumin-bound paclitaxel use in these diagnoses with improved cost effective care and value enhancement. Methods: We analyzed all albumin-bound paclitaxel requests for FDA approved indications from April 2013 to June 2014. Requests withdrawn by the treating oncologist after OA consultation were compared with albumin-bound paclitaxel persistence over these five consecutive quarters. Financial outcomes of voluntary oncologist withdrawal of albumin-bound paclitaxel-based therapy in favor of another taxane were calculated as per standard Medicare reimbursement rates. Results: Over the entire 15 month span, we received a total of 265 evaluable albumin-bound paclitaxel requests, on a total of 181 patients. Ninety-two percent (155/168) of requests for albumin-bound paclitaxel with gemcitabine in pancreatic cancer were automatically approved by Oncology Analytics’ web based software. One third each of the requests for breast cancer (12/37, 32.43%) and NSCLC (21/60, 35%) were withdrawn by the requesting MD after OA consultation. Changing albumin-bound paclitaxel to another taxane reduced pharmaceutical costs by approximately $1,124,115 for these 15 months, or $74,941.00 monthly. Conclusions: When paclitaxel or docetaxel are safe and effective alternatives to albumin-bound paclitaxel, OA consultation enhances cancer care quality and value.

33 Background: The Wall Street Journal recently identified that the highest rates of use of erythropoietin to Medicare-covered persons with cancer in the United States was by 11 oncologists who practiced in Florida (WSJ, June 20, 2014). We asked a related, but similar question: Could chemotherapy claims databases be used to identify individual physicians in the southeastern United States who had high rates of prescribing five expensive oncology agents: levoleucovorin (Fusilev), palonosetron plus fosapretitant (Aloxi+Emend), peg-filgastrim (Neulasta), albumin-paclitaxel (Abraxane), and epoetin/darbepoetin? Methods: Chemotherapy requests for more than 2,000 oncologists who practiced in the southeastern United States for the years 2012- 2014 were reviewed. A “high user” oncology provider for a specific drug was operationally defined as an individual whose number of prescriptions for the specific drug was more than 2 standard deviations above that for other oncology providers whose chemotherapy requests were also contained in the same database. Results: Two out of 1,479 oncology providers were identified as “extremely high users” of expensive oncology drugs (operationally defined as a high user for 5 of the 5 study drugs), two were “very high users” of expensive oncology drugs (a high user for 4 of the 5 study drugs), and 25 were “high users” (a high user for three of the five study drugs). The overwhelming majority of oncology providers (1,450) were neither extremely high, very high, nor even high users of the five study drugs. Conclusions: In the Southeastern United States, a small number of oncology physicians are extremely high, very high, and high users of expensive oncology drugs. Additional studies are needed to evaluate case-mix and other patient-related factors that might explain this finding. Focused quality improvement initiatives might also be considered. [Table: see text]

248 Background: Among patients with early stage non-small cell lung cancer (NSCLC), appropriate use of adjuvant chemotherapy is an important determinant of survival. Existing level 1 data, which includes analysis of five cisplatin-based phase III trials (IALT, BLT, ALPI, ANITA, NCIC-CTG-JBR.10), two carboplatin-based phase III trials (CALGB 9633 and NATCH Trial), and two meta-analyses (LACE, MRC), demonstrate only cisplatin-based adjuvant chemotherapy regimens enhance overall patient survival. Most importantly, these studies also reveal that survival advantage from adjuvant chemotherapy does not extend to stage I patients, but only to stage II-IIIA patient subgroups. Unplanned a posteriori subset analyses indicate the possibility that certain stage I NSCLC with one or more "high risk" characteristics may benefit from cisplatin-based adjuvant chemotherapy. This hypothesis must be properly tested before it can be adopted. We, herein, hypothesize that many US stage I NSCLC patients are routinely treated in the adjuvant setting with regimens that have not demonstrated level one overall survival benefit. Methods: We examined chemotherapy request data for stage I & II NSCLC, submitted to a private health insurer by oncologists for the adjuvant treatment of NSCLC patients in the southeast US from January 2011 through May 2014. Results: Overall, 25% (67/264) of adjuvant chemotherapy requests were for stage I NSCLC patients (potential overuse). The frequency of these requests has increased over time: 17% in 2011, 20% in 2012, 30% in 2013, 34% in 2014. Four out of five of patients with stage I NSCLC (52/67) were given carboplatin-based regimens, while only one in five (19%, 13/67) received cisplatin-based regimens, and 3% (3/67) were pemetrexed-based regimens (potential misuse). Conclusions: High misuse and overuse rates of adjuvant chemotherapy for stage I NSCLC are observed among the privately insured populations of Florida, Texas and Georgia. Quality improvement initiatives in this patient population may be indicated to prevent potential harm from treatments advised against by ASCO, ESMO, NCIC, NCCN and UK guidelines.

249 Background: Oxaliplatin-containing regimens are among the most efficacious adjuvant treatments for locally-advanced colon cancer, although significant toxicity can occur. Because of relevant level I data, the NCCN revised its guidelines in 2012, recommending omission of oxaliplatin from combination adjuvant chemotherapy regimens for older patients (>70yo) with colon cancer. We examined prescribing behavior of oncologists between 2009 and 2014 to evaluate how rapidly NCCN guidelines were adopted into practice. Methods: This is a retrospective observational study of chemotherapy request data from more than 2,000 community oncologists in the southeastern United States. We examined 57 consecutive months of chemotherapy requests for stage II and III colon cancer patients 70 years and older, based on three epochs. During the middle epoch, one phase III trial evaluating oxaliplatin-containing regimens as adjuvant chemotherapy (NSABP C-07), and a revised 2012 NCCN guidelines, each supported omission of oxaliplatin from adjuvant chemotherapy regimens for older persons with colon cancer. Multivariate analyses evaluated associations among patient characteristics (age, gender, and performance status), disease stage, and time-period, with the odds of receiving oxaliplatin-containing regimens as adjuvant chemotherapy. Results: Among 266 persons with stage II or III colon cancer 70 years of age and older, over the six-year span, most adjuvant chemotherapy requests (184/266, 69.2%) contained oxaliplatin. Older age, male gender, and poor performance status were associated with significantly lower odds of receiving oxaliplatin-containing adjuvant chemotherapy regimens (p

36 Background: Rituximab maintenance for indolent, incurable non-Hodgkin lymphoma (NHL) remains controversial. NCCN supports maintenance rituximab for a span of up to two years as an alternative to watchful waiting following induction therapy. At least a dozen scientific papers have been published describing rituximab maintenance results; none has demonstrated overall survival benefit. The strongest data support comes from the PRIMA phase III trial which showed an increased PFS but no survival advantage. Increased toxicity, however, is clear and can be serious. Reports of progressive multifocal leukoencephalopathy, a rapidly fatal neurodegenerative disease, should be of especial concern to patients whose disease course can span many years. Oncology Analytics (OA) enhances cancer care quality and value by providing oncology decision-support to providers in SE USA. We hypothesized that the use of maintenance rituximab in this area of the country produces profound cost and real risk for a highly uncertain benefit to this population. Methods: We reviewed all requests for rituximab maintenance for low-grade NHL submitted by oncology practices to a major health insurer in one US region from Jul 2009-May 2014. We calculated the cumulative cost for blanket approval of such requests and the savings associated with our decision-support discussions of this questionable but NCCN-compliant practice. Results: 470 requests for maintenance rituximab for low-grade NHL were initiated within this 59-month span. The proportion of maintenance rituximab requests relative to the total chemotherapy requests decreased consistently over time, from 4.5% in the first six months of OA involvement in 2009, down to 1.5% in May 2014. The annual cost of rituximab maintenance, which depends on the dose schedule, ranges from about $30,000 to $40,000 per year. Additionally, we discovered many rituximab maintenance requests for durations exceeding two years without evidence-based support, most of which were rescinded after OA intervention. Conclusions: Ongoing OA intervention reduces risk of toxicity and enhances the quality and value of cancer care for these patients.

e18504 Background: Adjuvant chemotherapy is recommended for certain non-small cell lung cancer (NSCLC) patients in effort to improve survival and prevent disease recurrence. Many patients can be cu...

e14520 Background: Cancer is a disease of old age. Colorectal cancer (CRC) is among the most frequent solid tumors of elderly. Over the past four decades, progressively more efficacious and more to...

9654 Background: Level 1 data, multiple national guidelines, and ASCO Choosing Wisely policy recommend that GFs be employed if the risk of febrile neutropenia (FN) exceeds 20%. Virtually every comm...

Fibrinogen Richfield exemplifies a dysfibrinogen associated with a life-long thrombotic tendency. The evaluation of this novel case indicates that, like similar thrombotic dysfibrinogenemias, the abnormal protein polymerizes abnormally and demonstrates impaired clot dissolution. A survey of other cases of dysfibrinogenemia indicates that the relatively common abnormalities of Fibrinopeptide A release are generally asymptomatic or associated with bleeding, polymerization abnormalities are likely to be asymptomatic or associated with thrombosis (or occasionally bleeding), and complex abnormalities or additional, independent hemostatic defects are rather common. Thrombin and Reptilase clotting times are not helpful in distinguishing between the subsets, but clinical history, fibrinopeptide release, and polymerization studies may be useful. Abnormalities of fibrinogen function tend to correlate with changes in molecular domains related to binding and hydrolysis.

Certain antiphospholipid antibodies, particularly those associated with arterial thrombosis, reduce vascular prostacyclin production. Studies were conducted to determine whether antibody-mediated inhibition of phospholipase A2 accounts for this effect. In this report we present evidence that purified antiphospholipid antibodies reduce phospholipase A2 activity toward phospholipid substrates, both in vitro and in a defined system. Purified immunoglobulin, obtained from patients at risk for thrombosis who had plasma antiphospholipid antibodies, impaired prostacyclin generation after endothelial stimulation with thrombin or the calcium ionophore A23187. The release of arachidonate in response to A23187 was reduced in endothelial cells pretreated with antibody; the metabolism of exogenous arachidonate to prostacyclin was normal. Thrombin-induced synthesis of platelet-activating factor, which follows phospholipase A2-mediated generation of lysophosphatidylcholine, was also inhibited in parallel with the inhibition of prostacyclin generation. Phospholipase A2 activity was determined in a defined test system with two phospholipases A2. The hydrolysis of fatty acid was less in the presence of patient immunoglobulin than in buffer alone or with normal immunoglobulin. Inhibition by antibody was present at a range of phospholipase concentrations. Antiphospholipid antibodies, purified from patient serum by adsorption to and subsequent elution from immobilized cardiolipin or phosphatidylserine, also inhibited phospholipase A2 activity. The data support our conclusions that purified antiphospholipid antibodies inhibit endothelial phospholipase A2 activity in response to thrombin or ionophore and that phosphatidylcholine in a common metabolic precursor of both prostacyclin and platelet-activating factor. In a defined enzyme assay, inhibition by antiphospholipid antibody of phospholipase A2 activity does not require additional cofactors.

We have investigated whether endothelium-derived relaxing factor (EDRF) and nitric oxide (NO), a substance proposed to be one of the EDRFs, could elicit biochemical and biological responses in rat glomerular mesangial cells (MC). In wells with MC alone, guanosine 3',5'-cyclic monophosphate (cGMP) levels were 2.6 +/- 0.6 fmol/microgram protein, and bradykinin did not affect these levels, whereas in coincubation experiments with bovine aortic EC and rat MC, cGMP levels in MC increased to 44.6 +/- 21 fmol/micrograms protein after bradykinin stimulation (P less than 0.05). This effect was potentiated by superoxide dismutase and inhibited by hemoglobin and L-NG-monomethyl arginine, a specific inhibitor of EDRF synthesis. Increases in cGMP were also observed when MC were incubated directly with NO and were potentiated by superoxide dismutase and inhibited by hemoglobin. We also tested whether NO could inhibit angiotensin II (ANG II)-induced reductions in cross-sectional area (CSA) of MC. When MC were exposed to ANG II only, 65% of the cells underwent a significant reduction in CSA, as measured by digital image analysis. However, when MC were incubated with ANG II and NO, only 10% of cells responded (P less than 0.04). These studies demonstrate that EDRF and NO induce significant biochemical and functional responses in rat glomerular MC and suggest that communication between EC and MC may be important in regulation of glomerular function.

SummaryActivation of coagulation occurs at inflammatory sites following the ingress of mononuclear cells, and may result from alterations in the vessel wall. Since the monokine, interleukin 1, initiates diverse responses to inflammation, its ability to enhance vascular procoagulant activity was studied. Interleukin 1-treated cultured human endothelial cells acquired elevated levels of the procoagulant, tissue factor. This required de novo protein synthesis, was maximal at 2 h after exposure to interleukin 1, and resulted in persistently elevated cellular procoagulant activity. Tissue factor was later expressed (6-24 h) on the surface of uninjured endothelial cells. Endothelial cell procoagulant production and expression in response to interleukin 1 could be dissociated from endogenous prostaglandin metabolism, being insensitive to hydrocortisone, indomethacin, eicosatetrayionic acid and exogenous arachidonic acid. In addition, no increase in prostaglandin synthesis occurred during the interval in which tissue factor was synthesized. We therefore conclude that interleukin 1 stimulates endothelial synthesis and surface expression of tissue factor by a prostaglandin-independent mechanism.

Human umbilical vein endothelial cells were more sensitive to hydrogen peroxide lysis than cow pulmonary artery endothelial cells. Conversely, activated neutrophils which utilize hydrogen peroxide-mediated cell cytotoxicity cell mechanisms were more toxic to the cow pulmonary artery cells. This discordance was not related to neutrophil adhesion to either cell type or cell passage number. The antioxidant profiles of the endothelial cells revealed that cow pulmonary artery cells were rich in catalase to consume bolus hydrogen peroxide presented to them, while human umbilical vein endothelial cells utilize glutathione peroxidase-linked mechanisms to detoxify a slower more sustained release of hydrogen peroxide generated by neutrophils. Endothelial cells from different species and sites may utilize diversified antioxidant protective mechanisms.

Twenty depressed patients given 150 mg of imipramine nightly improved as well as twenty depressed patients given imipramine in three daily doses of 50 mg. An earlier improvement was noted on the single dose schedule, whereas a better long-term effect was suggested for the divided dosage. No unusual toxicity or side effects were connected with the single dose schedule.

Two groups of inpatients who were initially misdiagnosed are described. The pseudoschizophrenics showed little affect and had histories of exotic and sensational behavior; the initial misdiagnosis of schizophrenia appeared to be a moral censure. The pseudoneurotic schizophrenics (mistakenly diagnosed at admission as nonschizophrenic) had more affect and were frequently pregnant, affiliated with the medical profession, or twins; these diagnostic mistakes appeared to be attempts to protect someone from the label of schizophrenia.

Gentlemen ! In the past few years I have seen a number of patients the peculiarity of whose illness escaped me heretofore, I must admit, because I neglected to study them in a systematic manner. To me the observations seemed interesting enough to report and to hear your opinion concerning them, particularly since they also merit no small practical interest. These patients have a number of common features which justify grouping them together as a distinct entity. I will select, from the four cases which I have seen, the outstanding features and sketch them for you. The most obvious sign which they present consists of their inability to answer correctly the simplest questions which are asked of them, even though by many of their answers they indicate that they have grasped, in a large part, the sense of the question, and in their answers they betray at once a baifling ignorance and a surprising lack of knowledge which they most assuredly once possessed, or still possess.

H. R. Schoolcraft recorded two tales he heard from Chippewas in Michigan during the 1820s which exemplify two types of near-death experiences (NDE). The first tale has autoscopic, as well as specifically Native American, elements; the second, in a similar way, contains elements of the transcendental type. These are discussed with reference to local origin, influence of white American culture, and universality.

Sounds with slow (less than 20 Hz) fluctuations may elicit the hearing sensation fluctuation strength. For AM tones, neural correlates of fluctuation strength were searched in the auditory cortex of unanesthetized squirrel monkeys. To enable a comparison of psychophysical and physiological data, the 'modulation' of the peristimulus time histogram was fitted by a sinusoidal function. The dependence of the amplitude of this function on modulation frequency, modulation depth and sound pressure level was often comparable to the dependence of fluctuation strength on the same stimulus parameters. In particular, as a function of modulation frequency, the neural data also show a bandpass characteristic at low modulation frequencies as was found for the hearing sensation fluctuation strength.

A review of records and telephone contact with authors of reports pertaining to the use of propranolol in psychiatric patients revealed no systematic comparison of its efficacy in managing behavioral disturbances in black patients as compared with white patients. Too few black patients have been included in studies to reach any conclusions about the efficacy of propranolol, or whether race is a differentiating factor.

The presence of the "lupus anticoagulant" (LA) predicts a clinical syndrome of excessive arterial, venous and microvascu-lar thrombosis. LA is an antibody which reacts with negatively charged phospholipid (PL) species in vitro. Since PL is involved in many aspects of the regulation of thrombosis, we postulated that LA might modify one or more of the membrane-(PL-dependent reactions of platelets and endothelial cells (EC). Blood samples from 20 patients with a history of thrombosis were tested for the presence of LA (kaolin PTT) and titres determined. LA-positive (LA+) sera and plasma were compared to LA-negative (LA−) samples from normal donors (n=6) or patients who had lupus but no clinical thrombosis (n=4). These specimens were tested in a panel of assays. The thrombin-stimulated release of prostacyclin (PG12) from cultured human EC was markedly reduced (52%±12.5 s.e.) by preincubation of the EC with LA+ sera (30 minutes). Purified LA+ IgG from one patient reproduced this effect. Thrombin induction of EC synthesis of the procoagulant, tissue factor-which is dissociable from prostaglandin metabolism-was also inhibited by LA+ sera. Normal platelets incubated in LA+ plasma became refractory to thrombin (1 unit/ml) but retained their responsiveness to epinephrine and ADP. The reduced responsiveness to thrombin was not due to altered (specific or total) binding of thrombin. The cleavage of Factor X by Factor VII requires PL as a co-factor for the EC procoagulant, tissue factor (TF). Unlike the inhibitory effect of LA on thrombin activation of EC and platelets, this distinct membrane-(PL-) dependent function was variably enhanced by LA+ sera. Brief (20 min) exposure of EC to LA+ sera increased TF co-catalysis of Factor VII cleavage of Factor X (measured by chromogenic Xa substrate, S-2222) by up to 10 fold (p

Cultured human umbilical vein endothelial cells synthesize the procoagulant, tissue factor, after exposure to bacterial endotoxin. Wild-type lipopolysaccharide from Escherichia coli 0127:B8 stimulates a five- to 20-fold increase in cellular tissue factor. Similarly, rough or incomplete lipopolysaccharide subunits from mutant bacterial strains, or lipid A prepared by mild acid hydrolysis of whole endotoxin, are also stimulatory. In addition, a lipid A biosynthetic precursor, consisting of a phosphorylated glucosamine disaccharide substituted with four beta-hydroxymyristoyl residues, is stimulatory at nanomolar concentrations. Endothelial cell tissue factor is not detectable on the surface of undisrupted cells, but can activate clotting on the cell surface after oxidant-mediated cell injury. The procoagulant, tissue factor, is synthesized by endothelial cells after stimulation mediated by a moiety contained within the lipid A region of lipopolysaccharide. Exposure of clotting factors at the endothelial cell surface after cell injury suggests a mechanism for the microvascular thrombosis associated with disseminated intravascular coagulation with sepsis.

Activation of coagulation occurs at inflammatory sites following the ingress of mononuclear cells, and may result from alterations in the vessel wall. Since the monokine, interleukin 1, initiates diverse responses to inflammation, its ability to enhance vascular procoagulant activity was studied. Interleukin 1-treated cultured human endothelial cells acquired elevated levels of the procoagulant, tissue factor. This required de novo protein synthesis, was maximal at 2 h after exposure to interleukin 1, and resulted in persistently elevated cellular procoagulant activity. Tissue factor was later expressed (6-24 h) on the surface of uninjured endothelial cells. Endothelial cell procoagulant production and expression in response to interleukin 1 could be dissociated from endogenous prostaglandin metabolism, being insensitive to hydrocortisone, indomethacin, eicosatetrayionic acid and exogenous arachidonic acid. In addition, no increase in prostaglandin synthesis occurred during the interval in which tissue factor was synthesized. We therefore conclude that interleukin 1 stimulates endothelial synthesis and surface expression of tissue factor by a prostaglandin-independent mechanism.

The ratios between the modulation index (eta) for just noticeable FM of a sinusoidally modulated pure tone and the degree of modulation (m) for just noticeable AM at the same carrier and the same modulation frequency were measured at carrier frequencies of 0.125, 0.25, 0.5, 1, 2, 4, and 8 kHz. Signal levels were 20 dB SL and 50 dB SPL or 80 dB SPL. At low modulation frequencies, for example, 8 Hz, AM and FM elicit very different auditory sensations (i.e., a fluctuation in loudness or pitch, respectively). In this case, eta and m show different values for just noticeable modulation. Since both stimuli have almost equal amplitude spectra if eta equals m (m less than 0.3), the difference in detection thresholds reflects differences in the phase relation between carrier and sidebands in AM and FM. With increasing modulation frequency, the eta-m ratio decreases and reaches unity at a modulation frequency called the "critical modulation frequency" (CMF). At modulation frequencies above the CMF, the same modulation thresholds are obtained for AM and FM. Therefore, it can be concluded that the difference in phase between the two types of stimuli is not perceived in this range. At center frequencies below 1 kHz, where phase errors caused by headphones and ear canal presumably are small, the CMF is useful in estimating critical bandwidth.