The association between threatened preterm labour and perinatal outcomes at term: a population-based cohort study.

OBJECTIVE: To estimate the association between threatened preterm labour (TPTL) and perinatal outcomes of infants born at term. DESIGN: A population-based cohort study of perinatal outcomes following TPTL <37 weeks of gestation with delivery at term. SETTING: Nova Scotia, Canada. POPULATION: All non-anomalous, singleton pregnancies ≥37 weeks of gestation without antepartum haemorrhage from 1988 to 2019. METHODS: Using data from the Nova Scotia Atlee Perinatal Database, TPTL was defined as pregnancies with a hospital admission between 20 and 37 weeks of gestation, with a diagnosis code denoting TPTL with administration of antenatal corticosteroids, or with administration of any tocolysis. Poisson regression models were used to estimate the risk ratios (RR) with 95% CI of maternal and perinatal outcomes in women who had an episode of TPTL relative to those who did not. MAIN OUTCOME MEASURES: Birthweight for gestational age below the tenth centile and a composite of perinatal mortality or severe perinatal morbidity. RESULTS: Of 256 599 term deliveries meeting the inclusion criteria, 2278 (0.9%) involved TPTL. The risks of the primary outcomes were higher among those with TPTL relative to those without: birthweight for gestational age below the tenth centile (RR 1.24, 95% CI 1.11-1.39) and the composite of perinatal mortality/severe perinatal morbidity (RR 1.33, 95% CI 1.15-1.54). CONCLUSIONS: Although the prevalence of TPTL in term deliveries is low, affected pregnancies are at increased risk for adverse perinatal outcomes. Increased fetal surveillance should be considered in the management of pregnancies affected by TPTL.

I'll be there for you: The effects of exercise engagement on social support provision within undergraduate students' personal networks.

Objective: To use social network analysis to examine exercise participation relative to health and wellness support provision within students' networks. Participants: 513 undergraduates from a large private university completed online surveys. Methods: Multilevel modeling assessed exercise engagement at the individual and dyadic level and support provision from network members. Results: More support was perceived by first and second-year students and individuals who reported more exercise engagement. Significant others, roommates, siblings, female network members, and those who exercised often provided greater support. Greater support was reported when both the participant and their social tie were involved in the campus group-exercise program. Conclusion: This study suggests individual and dyadic-level exercise was related to undergraduates feeling more supported. Findings support campus group exercise programs as opportunities to create reciprocal supportive ties for college students. Future research could further explore ways exercise and social support, particularly in group settings, affect health and well-being.

Optimizing pain relief in a specialized outpatient palliative radiotherapy clinic: contributions of a clinical pharmacist.

PURPOSE: Bone metastases are the most common cause of cancer pain, with palliative radiotherapy (RT) the mainstay of treatment. However, relief from RT may be delayed, incomplete, or short-lived and therefore optimized pharmacologic therapy is essential. Our objective was to describe the contribution of the clinical pharmacist (CP) to an outpatient palliative RT clinic. METHODS: The Edmonton Symptom Assessment System, an 11-point scale for measuring nine symptoms, and other validated screening tools were administered, and a medication history performed by the CP. Baseline CP assessment also included opioid toxicity, need for supportive medications, and drug interactions. Anonymized clinical information was collected prospectively and descriptive statistics were compiled including themes of counselling performed by the CP. RESULTS: The CP reviewed 114 patients over 140 clinic visits (01/2007-12/2008). Median age was 68.3 years, 68.4% were male and 36.8% had prostate cancer. All symptoms improved or stabilized in ≥ 80% by 4 weeks. Median pain score was 6/10 (SD 2.6) at baseline, and 2.1/10 (SD 2.4) by week 4. Average morphine equivalent daily dose was 76.8 mg at baseline and 44.5 mg at week 4. CP assessment included screening for opioid toxicity (87.9%), recommending a change in analgesic (28.9%), and liaison with the community pharmacy (17.1%). Medication counselling took place in 84.3% of visits, on bowel routine (85.6% of the time), opioids (82.2%), and hydration (40.7%). CONCLUSIONS: The CP plays a key role in holistic patient assessment and optimization of pharmacologic therapy, contributing to improved symptom control of patients receiving palliative RT.

Social networks, group exercise, and anxiety among college students.

OBJECTIVE: This study aimed to evaluate the relationship between group exercise membership, social network characteristics, and general state anxiety in a sample of college students. Participants: 490 undergraduates from a private university in the southern US participated in the study. Methods: An egocentric network analysis was conducted to test whether demographic variables, leisure-time physical activity, group exercise membership, flourishing scores, and network variables were related to anxiety. Results: Regression analyses (R2 = .174, F = 7.650, p < .0001) suggest group exercise membership (ß = -.105, p = .034) and flourishing scores (ß = -.342, p < .0001) were related to lower anxiety scores, while being a racial/ethnic minority (ß = .094, p = .036), and having personal networks composed of more people who exercise often (ß = .100, p = .025), were related to higher anxiety scores in this sample. Conclusions: Findings suggest a connection between group exercise membership, activity habits of peers, and anxiety. Encouraging group exercise participation could be an effective way of combating anxiety for college students.

COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.

One year into the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), effective treatments are still needed 1-3 . Monoclonal antibodies, given alone or as part of a therapeutic cocktail, have shown promising results in patients, raising the hope that they could play an important role in preventing clinical deterioration in severely ill or in exposed, high risk individuals 4-6 . Here, we evaluated the prophylactic and therapeutic effect of COVA1-18 in vivo , a neutralizing antibody isolated from a convalescent patient 7 and highly potent against the B.1.1.7. isolate 8,9 . In both prophylactic and therapeutic settings, SARS-CoV-2 remained undetectable in the lungs of COVA1-18 treated hACE2 mice. Therapeutic treatment also caused a dramatic reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg - 1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 had a very strong antiviral activity in the upper respiratory compartments with an estimated reduction in viral infectivity of more than 95%, and prevented lymphopenia and extensive lung lesions. Modelling and experimental findings demonstrate that COVA1-18 has a strong antiviral activity in three different preclinical models and could be a valuable candidate for further clinical evaluation.

Non-algorithmic access to calendar information in a calendar calculator with autism.

The possible use of a calendar algorithm was assessed in DBC, an autistic "savant" of normal measured intelligence. Testing of all the dates in a year revealed a random distribution of errors. Re-testing DBC on the same dates one year later shows that his errors were not stable across time. Finally, DBC was able to answer "reversed" questions that cannot be solved by a classical algorithm. These findings favor a non-algorithmic retrieval of calendar information. It is proposed that multidirectional, non-hierarchical retrieval of information, and solving problems in a non-algorithmic way, are involved in savant performances. The possible role of a functional rededication of low-level perceptual systems to the processing of symbolic information in savants is discussed.

Verbal memory impairments in schizophrenia associated with cortical thinning.

Verbal memory (VM) represents one of the most affected cognitive domains in schizophrenia. Multiple studies have shown that schizophrenia is associated with cortical abnormalities, but it remains unclear whether these are related to VM impairments. Considering the vast literature demonstrating the role of the frontal cortex, the parahippocampal cortex, and the hippocampus in VM, we examined the cortical thickness/volume of these regions. We used a categorical approach whereby 27 schizophrenia patients with 'moderate to severe' VM impairments were compared to 23 patients with 'low to mild' VM impairments and 23 healthy controls. A series of between-group vertex-wise GLM on cortical thickness were performed for specific regions of interest defining the parahippocampal gyrus and the frontal cortex. When compared to healthy controls, patients with 'moderate to severe' VM impairments revealed significantly thinner cortex in the left frontal lobe, and the parahippocampal gyri. When compared to patients with 'low to mild' VM impairments, patients with 'moderate to severe' VM impairments showed a trend of thinner cortex in similar regions. Virtually no differences were observed in the frontal area of patients with 'low to mild' VM impairments relative to controls. No significant group differences were observed in the hippocampus. Our results indicate that patients with greater VM impairments demonstrate significant cortical thinning in regions known to be important in VM performance. Treating VM deficits in schizophrenia could have a positive effect on the brain; thus, subgroups of patients with more severe VM deficits should be a prioritized target in the development of new cognitive treatments.

Neural correlates of taste perception in congenital blindness.

Sight is undoubtedly important for the perception and the assessment of the palatability of tastants. Although many studies have addressed the consequences of visual impairment on food selection, feeding behavior, eating habits and taste perception, nothing is known about the neural correlates of gustation in blindness. In the current study we examined brain responses during gustation using functional magnetic resonance imaging (fMRI). We scanned nine congenitally blind and 14 age- and sex-matched blindfolded sighted control subjects, matched in age, gender and body mass index (BMI), while they made judgments of either the intensity or the (un)pleasantness of different tastes (sweet, bitter) or artificial saliva that were delivered intra-orally. The fMRI data indicated that during gustation, congenitally blind individuals activate less strongly the primary taste cortex (right posterior insula and overlying Rolandic operculum) and the hypothalamus. In sharp contrast with results of multiple other sensory processing studies in congenitally blind subjects, including touch, audition and smell, the occipital cortex was not recruited during taste processing, suggesting the absence of taste-related compensatory crossmodal responses in the occipital cortex. These results underscore our earlier behavioral demonstration that congenitally blind subjects have a lower gustatory sensitivity compared to normal sighted individuals. We hypothesize that due to an underexposure to a variety of tastants, training-induced crossmodal sensory plasticity to gustatory stimulation does not occur in blind subjects.

Parathyroid hormone fragments may stimulate bone growth in ovariectomized rats by activating adenylyl cyclase.

PTH is regarded conventionally as a catabolic hormone that stimulates osteoclastic resorption of bone. However, it has been known since 1932 that intermittent pulses of PTH stimulate bone formation in animals and humans. PTH independently activates two signal mechanisms: one that stimulates adenylyl cyclase and one that stimulates protein kinase C (PKC). The goal of this study was to use the 3- to 5-month-old ovariectomized (OVX) rat model to determine which of the two signal mechanisms is responsible for the anabolic action of PTH on bone. OVX triggered a large loss of trabecular bone without significantly affecting the normal slow growth of cortical bone in the distal halves of the femora. Daily injections of human hPTH(1-34) fragment (1 nmol/100 g body weight), which stimulated both adenylyl cyclase and membrane-associated PKC activity in osteoblast-like ROS 17/2 rat osteosarcoma cells, stimulated the growth of both cortical and trabecular bone in the OVX rats. Daily injections of the same dose of hPTH(1-31), which stimulated adenylyl cyclase but not PKC in ROS 17/2 cells, stimulated trabecular bone growth in the OVX rats less effectively than hPTH(1-34), but it stimulated cortical bone growth as rapidly and as dramatically as hPTH(1-34). Injections of equimolar amounts of desamino-hPTH(1-34) [N-propionyl(2-3)hPTH-amide], which stimulated PKC as strongly as hPTH(1-34) in ROS 17/2 cells but had a drastically reduced ability to stimulate adenylyl cyclase, or injections of recombinant hPTH(8-84) which stimulated PKC only in the ROS 17/2 cells, did not stimulate cortical or trabecular bone growth in the OVX animals. Thus, cyclic AMP and cyclic AMP-dependent protein kinases may be the primary mediators of the anabolic action of intermittent pulses of PTH on bone in OVX rats.

Further definition of the protein kinase C activation domain of the parathyroid hormone.

The protein kinase C (PKC) activation domain of the parathyroid hormone (PTH) was believed to be the 28-34 region of the molecule. We have now shown that PTH-(29-32) is the smallest PTH fragment that can stimulate significantly membrane-associated PKC activity in ROS 17/2 rat osteosarcoma cells. As was previously shown for full-length PTH-(1-84) and the fully bioactive PTH-(1-34) fragment, there were two peaks in the PKC response to PTH-(29-32): one peak was obtained with low picomolar concentrations and the other with much higher nanomolar concentrations of the fragment. The PKC-activating ability was unaffected by the loss of Asn33 and Phe34, but it was abolished by removing His32. Thus, the PTH-(28-31) and PTH-(29-31) fragments did not stimulate membrane-associated PKC activity. The much larger PTH-(1-31) fragment also did not stimulate membrane-associated PKC activity, although it stimulated adenylyl cyclase as strongly as PTH-(1-34). This functional sensitivity to the loss of the polar His32 was not caused by a specific need for His or another polar amino acid in this position because replacing it with the apolar Leu did not abolish adenylyl cyclase or PKC activation. It is concluded that the minimum, fully functional PKC activation domain of the PTH molecule is Gln29-Asp30-Val31-His32.

Protein kinase C-activating domains of parathyroid hormone-related protein.

N-terminal fragments of PTH-related protein (PTHrP), PTHrP-(1-34), and PTHrP-(1-40) stimulated both adenylyl cyclase and a mechanism that increases membrane-associated protein kinase C (PKC) activity in ROS 17/2 rat osteosarcoma cells. There were two peaks in the PKC response to the N-terminal PTHrP fragments: one peak was obtained with picomolar and the other with nanomolar PTHrP concentrations. The PKC-stimulating picomolar concentrations of the PTHrP fragments did not detectably stimulate adenylyl cyclase, but the nanomolar concentrations did. Since a similar two-peak response of PKC activity was obtained with PTHrP-(28-34), the single, N-terminal PKC activation domain of the PTHrP is in the same 28-34 region of the molecule as that of PTH despite this region having different primary amino acid sequences in the two hormones. Unlike PTH, PTHrP has a second PKC activation domain, as indicated by the ability of picomolar concentrations of the PTHrP-(107-111) fragment to stimulate maximally membrane-associated PKC activity in the osteosarcoma cells.

The protein kinase-C activation domain of the parathyroid hormone.

The PTH activates both adenylate cyclase and a mechanism that increases membrane-associated protein kinase-C (PKC) activity. To define the hormone's PKC activation domain we have used a panel of PTH fragments and ROS 17/2 rat osteosarcoma cells as the target cells. PTH equally and maximally increased PKC activity in ROS 17/2 cell membranes at physiological concentrations between 1-50 pM and 5-50 nM, but not at intermediate concentrations or concentrations above 50 nM. The PKC-stimulating picomolar concentrations of PTH did not stimulate adenylate cyclase in ROS 17/2 cells, while the PKC-stimulating nanomolar concentrations of the hormone did stimulate adenylate cyclase, with an EC50 of 1-2 nM. Very high concentrations of PTH, such as 100 nM, that did not increase membrane PKC activity were still able to maximally stimulate adenylate cyclase. PTH fragments lacking the N-terminal amino acids needed for adenylate cyclase activation increased membrane PKC activity, and the PKC activation domain was found to lie within the 28-34 region of the PTH molecule. This was confirmed by showing that optimally effective picomolar concentrations of the human PTH-(28-34) fragment itself were able to increase membrane-associated PKC activity to the same extent as the optimally effective picomolar concentrations of the intact PTH-(1-84) or the larger PTH-(1-34) or PTH-(3-34) fragments.

Sequence of the ponA gene and characterization of the penicillin-binding protein 1A of Pseudomonas aeruginosa PAO1.

The nucleotide sequence of the ponA gene encoding the high molecular-mass penicillin-binding protein 1A (PBP1A) of Pseudomonas aeruginosa (Pa) PAO1 was determined and characterized. The predicted PBP1A protein of 822 amino acids (aa) has a calculated molecular mass of 91.2 kDa corresponding to the size of the protein expressed in vitro and in vivo. A penicillin-binding (PB) assay showed that the Pa ponA gene product covalently binds penicillin. The deduced PBP1A aa sequence has features typical of class-A high-molecular-mass PBPs: a highly hydrophobic N-terminus portion containing a potential transmembrane segment which might anchor the protein to the cytoplasmic membrane; an N-terminal module with the conserved boxes 1 (E86D(DN)F(AN)H(Y)G), 2 (G117GS(T)I(TM)Q), 3 (R139K(IN)E(ILL)AL) and 4 (R221R(NW)IL); a PB module with the conserved boxes 5 (S461SFK), (S520RN) and (K695TG); an internal extension at aa 297-407 between the N-terminal and PB modules; and a C-extension at the end of the PB module at aa 742 to 822. The highest percentage of similarity (62.8%) was found with the class A high-molecular-mass PBP1A of Escherichia coli (Ec) and Haemophilus influenzae. The observed extensive homology in the modular design of the Pa PBP1A with the bifunctional Ec PBP1A suggests structural and functional relationships between these proteins and refutes the proposed correspondence between Pa PBP1A and Ec PBP1B.

Gastrojejunal kinetics and the digestion of [15N]beta-lactoglobulin and casein in humans: the influence of the nature and quantity of the protein.

The evolution and luminal effects of different quantities of casein and beta-lactoglobulin were investigated in the upper jejunum of 35 volunteers who ingested 400 mL water with either beta-lactoglobulin or casein in either low or high doses (72.6 mmol N, Lbetalg; 71.7 mmol N, LCas; 368.2 mmol N, Hbetalg; 386.8 mmol N, HCas). The flow rate of the liquid effluents as well as the nitrogen movements were measured and the exogenous ([15N]) and endogenous nitrogen fractions analyzed in the upper jejunum after milk protein ingestion. The basal jejunal liquid flow rate (mL/min) was 3.88+/-1.84 and peaked in the 0-20 min period for water (9.92+/-3.72) and Lbetalg (7.27+/-3.08) and during the 20-40 min period for LCas (5.69+/-2.49), HCas (6.32+/-1.85), and Hbetalg (6.11+/-2.31). One hour after water, LCas, Lbetalg, Hbetalg, and HCas ingestion, 100%, 95%, 85%, 71%, but only 38% of the liquid phase of the meal were passed through the jejunum, respectively. The flow rate of the endogenous nitrogen was 12.93+/-5.22 mmol N/h before meal ingestion; remained unchanged after water, LCas or Hbetalg ingestion; but increased significantly (P<0.05) after Lbetalg and HCas ingestion. The net disappearance of exogenous nitrogen in the upper jejunum 240 min after HCas, Lbetalg, LCas and Hbetalg ingestion was 82.6+/-9.5%, 61.6+/-9.6%, 58.4+/-14.7%, and 44.7%+/-24.4%, respectively. The exogenous fraction of protein nitrogen recovered in the upper intestinal lumen represented 43.3% of the ingested Hbetalg nitrogen, but only 4.9% of the ingested HCas nitrogen. In conclusion, casein and beta-lactoglobulin present differences in both the intestinal kinetics of amino acid delivery and in the nature of the products in the intestinal lumen. These differences have to be taken into account from both nutritional and physiologic points of view for the utilization of these proteins in humans.

Thioamides: synthesis, stability, and immunological activities of thioanalogues of Imreg. Preparation of new thioacylating agents using fluorobenzimidazolone derivatives.

Imreg (Tyr1-Gly2-Gly3) is a well-known immunostimulant. However, it possesses a short half-life. Stabilized analogues of Imreg were prepared by a regioselective insertion in which peptide bonds at position 1,2 or 2,3 were replaced by thioamide linkages. This was achieved by using new thioacylating agents based on thioacyl-fluoro-N-benzimidazolone. The synthesis and properties of these reagents are described herein. This peptide modification enhanced significantly the half-life of the thioanalogues relative to Imreg in blood. The thioanalogues and Imreg were tested in vitro in T and B cell proliferation assays and for their ability to stimulate cytotoxic T-lymphocytes (CTLs). Only thiotyrosyl glycyl glycine 11 displayed some activity as evidenced by a weak stimulation of CTLs. On the basis of this activity and the increased stability, an in vivo immunological evaluation was undertaken. Immunophenotyping of 11 revealed a significant increase in activated CTL and NK cell populations in the spleen. This expansion was also accompanied by a significant stimulation of NK cells and the B cell proliferative response. Thioanalogues of Imreg were generally nontoxic, as exemplified by 11. The latter is a promising immunostimulant which may be targeted for cancer and viral infections, where CTLs and NK cells play an important role, or as a vaccine adjuvant where stimulation of antibody-producing B cells is important.

Synthesis and activity of 6-substituted purine linker amino acid immunostimulants.

A series of 6-substituted purinyl alkoxycarbonyl amino acids were synthesized and evaluated for their ability to stimulate cytotoxic T lymphocytes (CTLs) and the mixed lymphocyte reaction (MLR). A few of these compounds, in particular [[5-[6-(N,N-dimethylamino)purin-9-yl]pentoxy]-carbonyl]D-arginine (BCH-1393, 4a), displayed an in vitro stimulation of CTLs comparable to interleukin 2 (IL 2). BCH-1393 increased the CTL response between 10(-9) M and 10(-5) M. Further, this potent in vitro activity was reflected as a significant increase in CTL cell number in vivo. However, immunophenotyping of some of the other equipotent compounds did not reveal a parallel relative increase in CTLs in vivo. It was difficult to formulate a rigorous structure-activity relationship based on in vitro CTL activity. Nevertheless, the activity was dependent upon the nature of the 6-substituent on the purine, the type and stereochemistry of the amino acid, and the distance and spatial freedom between the purine and amino acid as defined by the length and rigidity of the linker. These compounds were generally nontoxic, as exemplified by BCH-1393. BCH-1393 is a promising immunostimulant which may be targeted for those disease states which require an increased CTL or TH1 type response.

Synthesis and activity of dipeptides, linked to targeting ligands, as specific NK cell enhancers.

Water soluble analogues of the lipophilic immunostimulant, octadecyl D-alanyl-L-glutamine, BCH-527, were synthesized and evaluated for the ability to stimulate natural killer (NK) cells. One of these compounds in which the octadecyl chain of BCH-527 was replaced with a shorter chain alcohol, 6-(D-alanyl-L-glutaminylamino)hexan-1-ol, 9, displayed an in vitro stimulation of NK cells comparable to that of interleukin 2 (IL 2). However, when the hydroxyl of 9 was linked to L-fucose to yield 1-beta-[6-(D-alanyl-L-glutaminylamino)hex-1-yl]-L- fucopyranose (BCH-2537, 1), the observed stimulation of NK cells was greater than that observed with IL 2. Further evaluation of these compounds revealed that the improved in vitro activity of BCH-2537 was more pronounced in vivo. That is, while both compounds significantly increased splenic NK cells, only BCH-2537 significantly increased the activity of these cells in vivo. In terms of a structure-activity relationship, NK cell activity was sensitive to minor structural modifications. It was influenced by conservative substitutions within the dipeptide, the length of the hydrocarbon chain, and the functionality at the end of the chain. No other compound enhanced NK cell activity to the extent exhibited by BCH-2537, although a few were equipotent to 9.

Influence of calcitriol on prolactin and prostaglandin production by human decidua.

Receptors for calcitriol are described in human decidua. They exhibit a dissociation constant of 35 +/- 6 pM and they are at concentrations similar to those found in other tissues (0.45 +/- 0.04 fmol/micrograms DNA). They are highly specific for calcitriol since neither of the other vitamin D3 derivatives nor the steroid hormone tested displaced labeled calcitriol from the receptor. Also, calcitriol at concentrations of 10(-13) to 10(-11) M stimulates prolactin secretion by dispersed decidual cells. At these concentrations, however, the hormone has no effect on prostaglandin production. The specificity of calcitriol action was further examined by studying the effect of estrogen, progesterone, testosterone, dexamethasone and cortisol, all at 10(-7) M, on the secretion of prolactin and prostaglandins. Under the conditions used in this study, the steroids have no effect on prolactin secretion; but dexamethasone significantly inhibits prostaglandin F2 alpha output by the cells. Taken together with previous studies from our laboratory demonstrating that decidua can synthesize calcitriol the present study indicates that this hormone has an autocrine effect on human decidual cells.

Music and emotion: perceptual determinants, immediacy, and isolation after brain damage.

This study grew out of the observation of a remarkable sparing of emotional responses to music in the context of severe deficits in music processing after brain damage in a non-musician. Six experiments were designed to explore the perceptual basis of emotional judgments in music. In each experiment, the same set of 32 excerpts taken from the classical repertoire and intended to convey a happy or sad tone were presented under various transformations and with different task demands. In Expts. 1 to 3, subjects were required to judge on a 10-point scale whether the excerpts were happy or sad. Altogether the results show that emotional judgments are (a) highly consistent across subjects and resistant to brain damage; (b) determined by musical structure (mode and tempo); and (c) immediate. Experiments 4 to 6 were designed to asses whether emotional and non-emotional judgments reflect the operations of a single perceptual analysis system. To this aim, we searched for evidence of dissociation in our brain-damaged patient, I.R., by using tasks that do not require emotional interpretation. These non-emotional tasks were a 'same-different' classification task (Expt. 4), error detection tasks (Expt. 5A,B) and a change monitoring task (Expt. 6). I.R. was impaired in these non-emotional tasks except when the change affected the mode and the tempo of the excerpt, in which case I.R. performed close to normal. The results are discussed in relation to the possibility that emotional and non-emotional judgments are the products of distinct pathways.

Measurement of heparin concentration in whole blood with the Hepcon/HMS device does not agree with laboratory determination of plasma heparin concentration using a chromogenic substrate for activated factor X.

UNLABELLED: Measurement of circulating heparin concentration has been suggested to optimize anticoagulation during cardiopulmonary bypass. The Hepcon/HMS device (Medtronic HemoTec, Inc., Parker, Colo.) uses heparin/protamine titration to quantitatively determine heparin concentration. Extensive validation of this instrument is still lacking. METHODS: Agreement between heparin concentrations measured by the Hepcon/HMS system and by laboratory determination was evaluated in 16 patients undergoing cardiac operations. For laboratory determinations, plasma heparin concentration was derived from the measure of anti-Xa activity by means of chromogenic substrate technique. The Hepcon/HMS instrument and cartridges measured whole blood heparin concentration. Samples were analyzed 5 minutes after administration of heparin, 15 and 30 minutes after the start of cardiopulmonary bypass, 5 minutes after aortic unclamping, at the end of cardiopulmonary bypass, and after administration of protamine. Data were plotted and interpreted according to the method of Bland and Altman: First, a difference less than 1.4 U/ml (i.e., +/- 0.7 U/ml) was chosen as acceptable, because it would not cause major difficulties in clinical interpretation; second, the difference between the two measurement techniques was plotted against the mean of the two measures. RESULTS: The mean difference (bias) between heparin concentrations derived by the Hepcon/HMS device and those obtained by laboratory determination was as expected for measures performed on whole blood versus plasma (1.45 U/ml). Nevertheless, heparin concentrations derived by the Hepcon/HMS device may be as much as 2.76 U/ml above or 6.17 U/ml below the concentrations measured in the laboratory, differences well outside the predetermined limits of agreement and clearly unacceptable for clinical purposes. CONCLUSION: We conclude that heparin concentrations determined with the Hepcon/HMS instrument do not agree with laboratory determination of heparin concentration. Monitoring of heparin concentrations during bypass with the Hepcon/HMS device cannot be recommended.