A role for xanthine oxidase in the control of fetal cardiovascular function in late gestation sheep.

Virtually nothing is known about the effects on fetal physiology of xanthine oxidase inhibition. This is despite maternal treatment with the xanthine oxidase inhibitor allopurinol being considered in human complicated pregnancy to protect the infant's brain from excessive generation of ROS.We investigated the in vivo effects of maternal treatment with allopurinol on fetal cardiovascular function in ovine pregnancy in late gestation. Under anaesthesia, pregnant ewes and their singleton fetus were instrumented with vascular catheters and flow probes around an umbilical and a fetal femoral artery at 118±1 dGA (days of gestational age; termca. 145 days). Five days later, mothers were infused I.V. with either vehicle (n =11) or allopurinol (n =10). Fetal cardiovascular function was stimulated with increasing bolus doses of phenylephrine (PE) following maternal vehicle or allopurinol. The effects of maternal allopurinol on maternal and fetal cardiovascular function were also investigated following fetal NO blockade (n =6) or fetal ß1-adrenergic antagonism (n =7). Maternal allopurinol led to significant increases in fetal heart rate, umbilical blood flow and umbilical vascular conductance, effects abolished by fetal ß1-adrenergic antagonism but not by fetal NO blockade. Maternal allopurinol impaired fetal α1-adrenergic pressor and femoral vasopressor responses and enhanced the gain of the fetal cardiac baroreflex. These effects of maternal allopurinol were restored to control levels during fetal NO blockade. Maternal treatment with allopurinol induced maternal hypotension, tachycardia and acid­base disturbance. We conclude that maternal treatment with allopurinol alters in vivo maternal, umbilical and fetal vascular function via mechanisms involving NO and ß1-adrenergic stimulation. The evidence suggests that the use of allopurinol in clinical practice should be approached with caution.

Prenatal hypoxia independent of undernutrition promotes molecular markers of insulin resistance in adult offspring.

Molecular mechanisms predisposing people to insulin resistance are starting to emerge. Altered insulin signaling for hepatic gluconeogenesis and muscle glucose uptake is thought to play a central role. Development under suboptimal conditions is also known to increase the risk of insulin resistance in adulthood. However, the partial contributions of reduced oxygen vs. nutrient delivery to the fetus, two common adverse conditions in utero, to developmental programming of insulin resistance remain unknown. The aim of this study was to determine the effects of developmental hypoxia or undernutrition on the expression of insulin-signaling proteins in liver and skeletal muscle in adult rat offspring. We show that the expression of hepatic phospho-Akt and muscle Akt2 were significantly reduced in offspring of hypoxic, relative to offspring from normoxic or undernourished, pregnancies. Hepatic Akt-1, Akt-2, and PKCζ protein expression was reduced in offspring from both hypoxic and undernourished pregnancies. Muscle GLUT4 expression was decreased in undernourished, and further decreased in hypoxic, offspring. These findings link prenatal hypoxia to down-regulation of components of hepatic and muscle Akt expression in adult offspring. Akt may represent a pharmaceutical target for clinical intervention against the developmental programming of metabolic disease resulting from prenatal hypoxia.

The interactive paradigm and a psychoanalytic paradox.

This paper examines the new "interactive" theorizing in the context of a fundamental paradox of psychoanalytic practice which has shaped theories of technique beginning with Freud. The paradox resides in the extent to which the work of psychoanalysis depends upon undependable capacities of the patient. This tension creates pressures on psychoanalytic practitioners which are often reflected in the creation of new theory in an effort to find "ways out" of the paradox. I propose that many of the significant historical shifts in our theories of technique, including the current "paradigm shift" emphasizing interactive aspects of psychoanalysis, have been surprisingly kindred efforts at "solving" the problems of this paradox.

Patients' and therapists' shared and unique views of the therapeutic alliance: an investigation using confirmatory factor analysis in a nested design.

The characteristically large general factor found in measures of the therapeutic alliance was analyzed by use of confirmatory factor analysis (CFA) in a nested design. Ratings by 38 therapists and their 144 patients on the California Psychotherapy Alliance Scales (CALPAS), the Revised Penn Helping Alliance Questionnaire (HAQ-R), and the Working Alliance Inventory (WAI) were adjusted for therapist effects. A set of models for patient and therapist ratings was tested with CFA, and a 3-factor model was confirmed, chi 2(4) = 7.19, p > .13; GFI = .98; RMSR = .02; CFI = 1.0. A shared-view factor (best represented by HAQ-R) accounted for 44% of patients' and 27% of therapists' variance. Unique factors (best represented by WAI) accounted for 56% of therapists' and 43% of patients' variance. Patient views split between HAQ (helpfulness) and WAI (goals, tasks) factors; The WAI factor was most expressive of therapist views. Patients and therapists tended to agree on helpfulness and on therapist clarity about goals and tasks. A multimeasure approach to alliance assessment is recommended.

Divorced women: individual differences in stressors, mediating factors, and adjustment outcome.

Individual differences in exposure and response to stress in a sample of 56 divorced mothers were examined. Compared with normative data, the sample reported significantly more negative life events, more psychiatric symptoms, and poorer social adjustment. Social support and income emerged as the mediating factors most strongly associated with adjustment outcome.

Effect of therapeutic digoxin antibodies on digoxin assays.

The introduction of therapeutic digoxin antibodies in the treatment of digoxin toxicity has resulted in spurious results in the many assays of cardioglycoside in serum of patients receiving this therapy. An evaluation of currently used assay methods was incorporated into a pilot Ligand Assay Survey Program of the College of American Pathologists to define which assays were unaltered by the presence of a therapeutic digoxin antibody (Digibind). Disparity of affinity constants of the therapeutic and kit antibodies is the most likely explanation for erroneous values. Specific methods are defined that appear to be free of this phenomenon.

The use of quantitative perfusion fluorometry to measure relative tumor and liver blood flow after transient microembolization.

Optimal chemotherapy delivery to the tumor depends on regional drug concentration, tumor perfusion, tissue drug uptake, and metabolism. Modulation of tumor blood flow has been used to improve tumor response to treatment. Transient microembolization is one method to alter regional blood flow, but its effects on relative changes in tumor and liver blood flow have not been previously measured. This study used quantitative perfusion fluorometry (QPF) to evaluate blood flow distribution in liver and tumor before and after hepatic arterial infusion of degradable starch microspheres (DSMs) in 10 New Zealand white rabbits. QPF was compared with radioactive xenon-133 washout, an established method for measuring blood flow. Xenon-133 was injected intraparenchymally and the clearance rate was measured allowing calculation of relative blood flow. QPF was then used to measure liver and tumor blood flow in a hepatic VX-2 tumor model after hepatic artery injection of DSMs. Initial tumor blood flow was 55% of liver flow. DSMs produced a significant and transient decrease in hepatic blood flow that was decreased to 40% of baseline after 25 min. Changes in relative hepatic blood flow after DSMs as measured by QPF correlated strongly with results obtained by xenon-133 washout (R = 0.97, P less than 0.01). Fluorometry's simplicity and reliability may be clinically useful to evaluate tumor blood flow characteristics.

Paget's disease of bone in patients with gout.

In a study designed to evaluate the radionuclide images in patients with gout, six (23%) of the 26 patients had clear evidence of Paget's disease of bone by technetium Tc 99m medronate imaging. A reference population consisting of 333 technetium Tc 99m medronate bone scans ordered for other reasons was reviewed, and only seven scans (2.1%) were found to have evidence of Paget's disease. This difference was found to be highly significant. All cases of Paget's disease were confirmed by independent radiologic evaluation. We conclude that there is a significant association between Paget's disease and gout, the basis for which is not yet known.

Labeled cells in the investigation of hematologic disorders.

Radiolabeling techniques for white cells, platelets, and erythrocytes are reviewed. The early studies using diisopropylfluoro-32P contributed to an understanding of the production and circulation of the blood elements, and 51Cr proved useful in localizing sites of cell migration or destruction. 111In-oxine has further improved the understanding of blood cell organ sequestration, and permitted combined kinetic and organ imaging studies. Radionuclide labels have been essential for the elucidation of various hematologic disorders, such as the neutropenias, thrombocytopenias, anemias, and polycythemia. Many new treatments, including monoclonal antibodies, have been evaluated with radionuclides.

Gadolinium DTPA (an NMR proton imaging contrast agent): chemical structure, paramagnetic properties and pharmacokinetics.

The structure, chemical properties, metabolic pathway and NMR contrast efficacy of Gadolinium-DTPA are described. This reagent has great promise as a contrast agent in NMR proton imaging, and clinical trials have been initiated in England and Germany.

Operating room event analysis.

A time/motion study performed in the Department of Anesthesiology at Ohio State University divided intraoperative events into three categories: (1) patient-centered, direct--activities that direct the anesthesiologist's attention to the patient; (2) patient-centered, indirect--observation of equipment or data related to patient status; and (3) non-patient-centered--activities that direct the anesthesiologist's attention away from the patient. Surprisingly, results of this study did not differ greatly from those of earlier investigators, who found that the anesthesiologist was distracted from the patient 46% of the time. Future studies and monitor development should address this problem by reducing non-patient-centered activities and distractions to the anesthesiologist during surgery.

The effects on synovial permeability and synovial fluid leukocyte counts in symptomatic osteoarthritis after intraarticular corticosteroid administration.

The mode of action of intraarticularly administered corticosteroids was studied. Fifteen patients with osteoarthritis and painful effusions had one knee injected with normal saline, triamcinolone hexacetonide 20 mg or prednisolone tebuate 20 mg. Fifteen millicuries of 99mTc-labeled albumin was given intravenously before and at various time intervals after the injection of the depot corticosteroid or saline. Whole blood and synovial fluid (SF) samples were used for blood to SF count rate ratio determinations. SF white blood cell counts (WBC) were also performed. The results indicated that intraarticular depot corticosteroids decreased synovial permeability and caused increases in the SF WBC. Moreover, decreases in pain and knee swelling correlated better with a decrease in vascular permeability, as assessed by the count ratio, than with SF leukocytosis.

Effect of water and fat on gastric emptying of solid meals.

Gastric emptying of solid egg meals tagged with 99mtechnetium sulfur colloid was studied in 10 normal subjects and in 6 patients after truncal vagotomy, antrectomy, and gastrojejunostomy (Billroth II) for peptic ulcer disease. Technetium sulfur colloid was found to bind more firmly to cooked egg whites than did the water soluble marker DTPA. Water accelerated gastric emptying in Billroth II patients to a greater degree than in normal subjects, in whom the effect of water was minimal and transient. Fat inhibited solid emptying both in normals and in Billroth II patients. These findings suggest that in humans there are jejunal receptors for fat that may inhibit gastric emptying even following truncal vagotomy.

Changes in level of precision of common ligand assays during a seven-year interval.

Nine commonly performed radioligand analyses were studied for periods of four to seven years in terms of change in level of precision. Consistent improvement in precision is generally observed, except in specific instances when pool characteristics are altered to study sensitivity and crossreactivity.

Laboratory intercomparison of commerical digoxin kits.

Results of recovery, precision, and effect of a protein deficient matrix on commercial digoxin assay kits is reviewed for pools distributed in 1978 by the Basic Ligand Assay Survey Program of College of American Pathologists. Variability among kits is present in terms of all three areas studied. Nevertheless, commonly used methods by participants have recovery rates approaching 100%; coefficients of variation are less than 10% at therapeutic serum levels.

Reproducibility of mean values of duplicate specimens in the Basic Ligand Assay Survey.

Three paired samples were distributed at three--six-month intervals in the Basic Ligand Survey during 1976. The stabilities of mean values obtained by widely used commercial kit procedures and by all methods for eight analytes are reported. Significant improvements in accuracy and long-term precision were identified in assays for digoxin and thyroxine during 1976. However, a number of assays yielded unstable mean values that affected both within--laboratory maintenance of quality control and medical usefulness of the results.