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Biomedical subjects

M E Weiss

Publications and source records attributed to M E Weiss.

34 records · Page 2Linked to original sources

Immunoreactivity of protamine preparations used to reverse heparin anticoagulation.

To determine if four commercially available intravenous protamine preparations differed in their ability to bind to human antiprotamine antibody, the sera of seven protamine-insulin-dependent diabetics who had experienced life-threatening reactions to intravenous protamine and whose sera contained a mean of 67.4 micrograms/ml (range, 16-200 micrograms/ml) of antiprotamine IgG antibody were evaluated. Each serum was preincubated with buffer and 0.0014 to 1.4 mg/ml of the four protamine preparations before addition to an agarose-based solid-phase radioimmunoassay using 125I-radiolabeled staph protein A as the detection protein. In the seven sera, the concentration of soluble protamine inhibiting 50% of protamine antibody (IC50) was determined by interpolating from points above and below 50% inhibition for each protamine preparation. No significant difference was found in the IC50 among the four different protamine preparations (P greater than 0.25; Kruskal-Wallis). The authors concluded that there is no significant difference in the immunoreactivity of the four commercial protamine preparations with human antiprotamine IgG antibody. Thus, there appears to be no advantage in using a particular intravenous protamine preparation based on immunoreactivity with human antiprotamine antibody.

Antibodies↗

Serial immunological investigations in a patient who had a life-threatening reaction to intravenous protamine.

Reactions to intravenous protamine include rash, urticaria, bronchospasm, hypotension, and/or pulmonary artery pressure elevation. We have previously shown that in diabetic patients receiving daily protamine-insulin injections, the presence of anti-protamine IgE or IgG antibodies are significant risk factors for acute, life-threatening reactions when protamine is given intravenously. To study protamine reactions further, we measured serum anti-protamine IgE and IgG antibody levels, in-vitro basophil histamine release and intracutaneous skin testing to protamine serially in an NPH-insulin dependent diabetic who had a severe, protracted anaphylactic reaction to protamine. At the time of his protamine reaction, his serum contained 8.5 ng/ml of anti-protamine IgE and 1.3 micrograms/ml of anti-protamine IgG antibody. One month following the reaction both anti-protamine IgE and IgG increased to 16 ng/ml (twofold rise) and 90.5 micrograms/ml (70-fold rise), respectively. With time, both anti-protamine IgE and IgG antibody declined. Serial intradermal skin tests using protamine sulphate did not discriminate between the protamine reactor and nine normal control subjects who had no prior exposure nor any demonstrable serum IgE antibody to protamine. In-vitro basophil histamine release to protamine sulphate was inconclusive in discriminating between the protamine reactor and normal control subjects. We postulate that protamine may be an incomplete or univalent antigen that must first combine with a tissue macromolecule or possibly heparin to become a complete multivalent antigen capable of eliciting IgE antibody-dependent mediator release.

Aged↗

Association of protamine IgE and IgG antibodies with life-threatening reactions to intravenous protamine.

Life-threatening reactions to intravenous protamine, administered to reverse heparin anticoagulation, have been reported with increasing frequency as a consequence of the escalating use of cardiac catheterization and coronary bypass surgery. Retrospective studies have shown that such reactions are more common in diabetic patients receiving daily subcutaneous injections of protamine-insulin preparations. To determine whether anti-protamine IgE or IgG antibodies might explain the increased risk for protamine reactions among patients with protamine-insulin-dependent diabetes, we conducted a case-control study of 27 patients (diabetic and nondiabetic) who had acute reactions to intravenous protamine and 43 diabetic patients who tolerated protamine without a reaction during diagnostic or surgical procedures. Cases and controls were grouped according to previous exposure to protamine-insulin preparations. In diabetic patients who had received protamine-insulin injections, the presence of serum antiprotamine IgE antibody was a significant risk factor for acute protamine reactions (relative risk, 95; P = 1.0 X 10(-5), as was antiprotamine IgG (relative risk, 38; P = 1.2 X 10(-5). No patients without previous exposure to protamine-insulin injections had serum protamine IgE antibodies. In this group, anti-protamine IgG antibody was a risk factor for protamine reactions (relative risk, 25; P = 0.0062). We conclude that in protamine-insulin-dependent diabetics, the increased risk of serious reactions when intravenous protamine was given appeared to be caused largely by antibody-mediated mechanisms. In nondiabetic subjects, the presence of protamine IgG was significantly associated with an increased risk of acute protamine reactions, although many nondiabetic subjects who had reactions had no IgG antibodies.

Adult↗

Rabbit F(ab')2 antihuman IgE is a universal skin test reagent in the evaluation of skin mast cell degranulation in vivo.

Antihuman IgE is often used to study basophil- and mast cell-mediator release in vitro but is infrequently used in vivo. To evaluate in vivo skin reactivity to anti-IgE, an affinity-purified rabbit F(ab')2 fragment of antihuman IgE was injected intradermally in 22 nonallergic and 27 allergic subjects. All 49 subjects (including a subject with less than 1 ng/ml of total serum IgE) had positive immediate cutaneous reactions to anti-IgE. Although total serum IgE level was weakly correlated (r = -0.51; p less than 0.005) with in vivo skin reactivity to anti-IgE for the entire population, allergic subjects did not have significantly increased skin reactivity compared to nonallergic subjects (p = 0.18), despite having higher total serum IgE levels (p less than 0.002). A late-phase cutaneous response (LPR) to anti-IgE occurred in 60% of the allergic and in 50% of the nonallergic subjects. Subjects with an LPR required approximately tenfold higher concentrations of anti-IgE to produce an immediate wheal of 10 mm compared to subjects who did not develop an LPR (p = 0.02), suggesting that the concentration of the stimulus injected is more important for the development of a LPR than the size of the immediate cutaneous response. Skin reactivity to codeine phosphate (a non-IgE-dependent secretagogue) was correlated with skin reactivity to anti-IgE (r = 0.47; p less than 0.05), suggesting that in vivo skin mast cell degranulation is partially a function of mast cell releasability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A protocol for performing reproducible methacholine inhalation tests in children with moderate to severe asthma.

Reproducibility of methacholine inhalation tests (MIT) over a 2-wk period has been established in adult populations, but similar studies demonstrating reproducibility in children are lacking. We set out to establish the reproducibility of MIT in children as a prerequisite for a study of the natural history of airway hyperreactivity in asthmatic children. Most inhalation testing is done in persons with mild asthma because the recommended time interval for the withholding of medications prior to bronchial challenge is poorly tolerated by more labile asthmatics. In order to evaluate asthmatics with more severe disease, we modified a standardized method of methacholine inhalation to include a three-tier pretest medication regimen and investigated the reproducibility of this MIT protocol in 11 children as young as 6 yr of age. The three tiers were designed to keep baseline FEV1 greater than or equal to 70% predicted since diminished baseline airway caliber may affect MIT results. Eight of the 11 children were bronchodilator-dependent, and two of the eight also required inhaled steroids. Eleven children (6 to 13 yr of age) underwent MIT, between December and March, 1 day, 1 wk, and 1 month after an initial test. The PD20FEV1 using cumulative breath units (BU) were compared. The range of PD20FEV1 in the 11 children was 0.27 to 14.4 BU, with nine subjects classified as severe (PD20FEV1 less than 2.5 BU). We found a high degree of reproducibility of MIT. The interest correlation coefficient (r) was 0.98 after 1 day, 0.95 after 1 wk, and 0.96 after 1 month.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Allergy to protamine.

Recent advances in medicine, such as cardiac catheterization, phoresis, dialysis, and cardiopulmonary bypass technology, have increased the need for heparin anticoagulation. To antagonize heparin's effect and prevent hemorrhagic complications after the procedure, protamine has likewise been used more frequently. With its increased use have come increased reports of adverse protamine reactions consisting of rash, urticaria, elevation of pulmonary artery pressure, systemic hypotension, and, at times, death. The elevation of pulmonary artery pressure, which appears to be a rather common occurrence in animals, may be an isolated finding without clinical consequences in humans. However, this pulmonary vasoconstriction may, when severe, lead to acute right-sided heart failure and systemic hypotension. Other protamine reactions involve a decrease in systemic vascular resistance and systemic hypotension without changes in pulmonary artery pressure. Causes of acute protamine reactions may involve the generation of anaphyatoxins and prostanoids either from protamine-heparin complexes or complement-fixing antiprotamine IgG antibodies, from inhibition of plasma Carboxypeptidase N, from crosslinking of cell-surface antiprotamine IgE on mast cells and basophils with subsequent mediator release, or from potentiation of IgE-mediated release of histamine through a polycationin-recognition site. Although we have come a long way in understanding the mechanisms by which protamine can cause its ill effects in humans, more work is clearly needed to define, in prospective studies, the incidence of and risk factors for protamine reactions in various patient groups, and to delineate more clearly which mechanisms are involved in each clinical type of acute protamine reaction. Hopefully, this will lead to strategies and protamine alternatives that will prevent or diminish, in frequency or severity, adverse protamine reactions. Alternatively, a clearer picture of the risk factors important for protamine reactions and the predictive value of diagnostic tests (e.g., protamine IgE antibody) can also minimize the clinical impact of this increasingly common adverse event.

Acute Disease↗

Laboratory and hospital testing of new infrared tympanic thermometers.

A patented approach to infrared thermometry based on the use of a standard pyrosensor has resulted in the development of two new infrared tympanic thermometers, one for professional use, the other for home use. Both were tested to evaluate accuracy in the laboratory and to evaluate equivalence to standards, correlation to standards, and precision in human subjects. Accuracy was found to be well within ASTM standards on both models. Mean ear temperatures were 0.2 degrees C below oral and 0.7 degrees C below bladder temperature. Correlations between ear and oral and ear and bladder temperatures were r = .77 to .84. Repeatability in the same ear was very high at r = .95 (left) and .97 (right). Reproducibility between left and right ear ranged from r = .89 to .92.

Equipment Design↗

Postpartum mothers' preferences for nighttime care of the neonate.

This study, conducted in response to issues raised during implementation of a dyad care delivery system, investigated preferences of postpartum mothers for nighttime care of the neonate. For dyad as well as traditional care subjects, the availability of individual care options emerged as a theme in both personal preference and preference based on available hospital accommodation. Significant differences existed between dyad and traditional care subjects on second choices for nighttime care and on environmental variables.

Attitude to Health↗

Infrared tympanic thermometry for neonatal temperature assessment.

OBJECTIVE: To investigate the accuracy and precision of infrared tympanic thermometer use with neonates by comparing with axillary and rectal measurements. DESIGN: Descriptive, comparative study. SETTING: Newborn nursery of a tertiary-level perinatal center. SUBJECTS: Thirty-four full-term newborns. INSTRUMENTS: Infrared thermometers were used to collect tympanic temperatures. An electronic thermometer was used to collect axillary and rectal temperatures. RESULTS: There was no significant difference between tympanic and axillary temperatures. The range of variation (95% CI) was +/- 0.7-.9 degrees C. The mean difference between tympanic and rectal measurements was 0.4 degrees C. The range of variation was +/- 0.7-0.75 degrees C. Right ear measurements produced the best approximation of axillary temperature, and protected ear measurements produced the best approximation of rectal temperature. The protected ear was 0.2-0.3 degrees C higher than the exposed ear. CONCLUSIONS: There was more variation between tympanic versus axillary and tympanic versus rectal measurements than between axillary and rectal measurements. Tympanic thermometry may be useful for rapid screening of neonatal temperature, but its usefulness for monitoring unstable neonates remains in question.

Axilla↗