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Biomedical subjects

J Schreiber

Publications and source records attributed to J Schreiber.

At least 91 records · Page 5Linked to original sources

Structured alarm systems for the operating room.

The administration of anesthesia may be viewed as a closed-loop control system consisting of three major components: the anesthesia system, the patient, and the system operator. A monitoring and alarm system during anesthesia should not be limited to only one of the three major components but must include monitoring of the patient, the performance of the anesthesia system, and the action of the system operator. For an alarm system to be successful when an adverse condition occurs, an alarm must be generated and identified, the problem identified and corrected, and the patient stabilized before injury results. The authors describe the characteristics of a structured alarm system that maximizes the time available to correct a potential problem before injury begins, that clearly identifies the cause of the problem, and that prioritizes alarms according to the urgency of the required response. Alarms should be easy to temporarily silence, have built-in alarm default settings to prevent the inadvertant use of settings meant for a previous patient, and have a graphic display that enables the operator to detect problems or trends before an alarm sounds.

Anesthesia, General↗

[The role of substance P in regulating bronchomotor tone and the pathogenesis of bronchial hyperreactivity].

Substance P (SP) is localized in sensory nerves of the respiratory tract in close connection to the effector cells of inflammatory and allergic bronchial diseases. SP is proposed to play an important role in the pathogenesis of bronchial asthma because of its ability to induce bronchoconstriction, vasodilatation and an edema of the mucous membrane and to enhance the secretion of tracheobronchial glands. Furthermore inflammatory and immune cells are influenced by SP. SP seems to have a complex action in the regulation of the bronchial tonus. Especially differences in the action of partial sequences of the peptide may be important in the pathogenesis of asthma.

Animals↗

Cytostatic activity of an estradiol-linked nitrosourea in MXT mammary carcinoma and L 5222 leukemia.

Investigation of 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine-estradiol-17-ester (CNC-ala-17-E2) and of the unlinked single agents 1-(2-chloroethyl)-1-nitrosocarbamoyl-L-alanine (CNC-ala) and estradiol in the MXT mammary carcinoma in vivo uncovered a significant antitumor activity only for CNC-ala-17-E2 at a non-toxic dose level (growth inhibition greater than 70%). In vitro investigations using the clonogenic assay had a comparable result: Here, too, CNC-ala-17-E2 was superior to the unlinked single agents. No difference in therapeutic activity between CNC-ala-17-E2 and CNC-ala could be observed in a transplanted rat leukemia (L 5222).

Animals↗

Direct ESR detection of a free radical intermediate during the peroxidase-catalyzed oxidation of the antimalarial drug primaquine.

Oxidation of the antimalarial primaquine by horseradish peroxidase and H2O2 was demonstrated by visible light absorption and ESR spectroscopy. Initial product analysis indicated a 15% yield of O-demethoxylation products, methanol and the quinone-imine derivative, and organic extractable polymeric material. Horseradish peroxidase was substituted by methemoglobin, and both enzymes showed greater activity at acidic pH values. During the enzymatic oxidation of primaquine, a drug-derived free radical was detected by direct ESR spectroscopy. A similar ESR spectrum was obtained during enzymatic oxidation of 6-hydroxyprimaquine at pH 9.0. Computer simulations of the ESR spectra obtained in normal and deuterated buffer indicated that the detectable free radical contains two primaquine moieties. This in vitro oxidation of primaquine to a free radical intermediate that is stable in the presence of oxygen might be considered a new mechanistic route for analyzing the pharmacological effects of primaquine.

Electron Spin Resonance Spectroscopy↗

A controlled family study of chronic psychoses. Schizophrenia and schizoaffective disorder.

Two hundred thirty-seven relatives of 48 patients with chronic psychosis, diagnosed as either schizophrenia or schizoaffective disorder, along with 380 relatives of psychiatrically normal controls, were studied using systematic diagnostic interviews, information from relatives, and review of medical records where appropriate. A variety of nonbipolar psychotic disorders was found in the relatives of the patients. Comparing relatives of patients with schizophrenia with relatives of patients with schizoaffective disorder, there was no tendency for schizoaffective diagnosis or acute psychoses to aggregate separately from schizophrenia. Increased incidence of bipolar disorder was found in relatives of patients with schizoaffective disorder but not in relatives of patients with schizophrenia. Incidence of major affective disorder (bipolar and unipolar) was increased in relatives of probands with both types of psychoses. If we subdivide the ill probands according to whether or not they had a history of substance abuse, relatives of probands with substance abuse had greater frequency of affective disorder and substance abuse, but there were not significant differences in the number of relatives with nonbipolar psychoses.

Adolescent↗

Osmoregulation of thirst and vasopressin during normal menstrual cycle.

Changes in osmoregulation during normal menstrual cycle were examined in 15 healthy women. In 10 women, studied repetitively during two consecutive menstrual cycles, basal plasma osmolality, sodium, and urea decreased by 4 mosmol/kg, 2 meq/l, and 0.5 mM, respectively (all P less than 0.02) from the follicular to luteal phase. Plasma vasopressin, protein, hematocrit, mean arterial pressure, and body weight did not change. In five other women, diluting capacity and osmotic control of thirst and vasopressin release were assessed in follicular, ovulatory, and luteal phases. Responses of thirst and/or plasma vasopressin, urine osmolality, osmolal and free water clearance to water loading, and infusion of hypertonic saline were normal and similar in the three phases. However, the plasma osmolality at which plasma vasopressin and urine osmolality were maximally suppressed as well as calculated osmotic thresholds for thirst and vasopressin release were lower by 5 mosmol/kg in the luteal than in the follicular phase. This lowering of osmotic thresholds for thirst and vasopressin release, which occurs in the luteal phase, is qualitatively similar to that observed in pregnancy and should be taken into account when studying water balance and regulation of vasopressin secretion in healthy cycling women.

Adult↗

An ESR study of nonenzymatic reactions of nitroso compounds with biological reducing agents.

The nonenzymatic reduction of nitrosobenzene (I), 2-nitroso-1-naphthol (II) and 2-nitroso-1-naphthol-4-sulfonic acid (III) with reducing agents such as NADPH, L-cysteine and N-acetyl-L-cysteine led to the formation of the corresponding hydronitroxide radicals, as confirmed with ESR spectroscopy. In addition to these radicals, a novel hydronitroxide radical, which was conjugated with GSH at the 4-position, was observed in the reaction of II or III with GSH. The formation of a hydronitroxide conjugated with GSH still retains the radical structure with its related redox chemistry. In this case, the formation of a GSH conjugate does not lead to the formation of chemically less reactive species.

Acetylcysteine↗

Experimental bronchoalveolar lavage in guinea pigs--a useful tool to investigate the intrabronchial release of substance P.

Bronchoalveolar lavage was performed in guinea pigs during bronchial challenge with capsaicin (100 micrograms/kg b.w. intravenously) and in control animals. Capsaicin caused a bronchoconstriction (VT minimal: 27.17% +/- 24.49). There was a significant amount of substance P-like immunoreactivity, detected by RIA in the lavage fluid of four of five animals challenged with capsaicin, but only in one of five controls. These results indicate that SPLIR is released into the bronchial lumen during capsaicin-induced bronchoconstriction. So bronchoalveolar lavage may be a useful tool to investigate the role of substance P in the bronchoconstrictor response induced by various stimulants.

Animals↗

Long-term effects of substance P on the isolated guinea pig trachea.

The undecapeptide substance P(SP) and its C-terminal sequence SP-5-11 induced a dose-dependent contraction of the isolated guinea pig trachea. SP-5-11 had a more potent bronchoconstrictive action than SP-1-11. The distal part of the isolated guinea pig trachea showed a greater reagibility to SP-5-11 than the proximal one. There was a continuous increase of the amplitude of the SP-1-11-induced contractions when the neuropeptide was added several times at one-hour intervals. Incubation with 10(-6) M SP-1-11 for 5 h reduced the reagibility of the isolated guinea pig trachea to acetylcholine.

Animals↗

Formation of glutathione-conjugated semiquinones by the reaction of quinones with glutathione: an ESR study.

The nonenzymatic reaction of the cytotoxic compounds menadione (2-methyl-1,4-naphthoquinone) and 1,4-naphthoquinone (a reactive metabolite of 1-naphthol) with reducing agents such as NADPH and glutathione led to the formation of semiquinone-free radicals, which were detected with electron spin resonance spectroscopy. In the presence of glutathione as a reducing agent, menadione and 1,4-naphthoquinone underwent net one-electron reduction and conjugation with glutathione. At higher concentrations of glutathione, 1,4-naphthoquinone formed the semiquinones of both the monoconjugate and the diconjugate. The naphthoquinone-glutathione conjugates should redox cycle in a manner already known for the menadione conjugate. The semiquinone intermediates could be detected only under a nitrogen atmosphere and are probably the primary oxygen-reactive species responsible for the redox cycling of menadione- and naphthoquinone-glutathione conjugates.

Benzoquinones↗

Generation of radical anions of nitrofurantoin, misonidazole, and metronidazole by ascorbate.

Nitrofurantoin, misonidazole, and metronidazole were reduced to their corresponding nitro anion radicals by ascorbate in anaerobic solutions at high pH. The nitrofurantoin anion radical could be detected at neutral pH. In neutral solutions, the nitro anion radicals of misonidazole and metronidazole were too unstable to be observed by electron spin resonance spectroscopy. At neutral pH, solutions containing ascorbate, nitrofurantoin, or misonidazole consumed oxygen. The addition of superoxide dismutase, catalase, or both superoxide dismutase and catalase decreased the rate of oxygen consumption. These results show that nitro anion radicals are formed by reduction with ascorbate, and superoxide anion radical and hydrogen peroxide are produced by reactions of these radicals with oxygen.

Anaerobiosis↗

Medroxyprogesterone acetate: receptor binding and correlated effects on steroidogenesis in rat granulosa cells.

Medroxyprogesterone acetate (MPA), a widely used synthetic steroid, was studied to determine both its effects on steroid receptors and steroidogenesis in the well-characterized rat ovarian granulosa cell model. Initial receptor binding studies showed MPA was as potent as progesterone and 10-fold less potent than R-5020 (an active synthetic progestin) in binding to progesterone cytosolic receptors in rat ovarian granulosa cells. MPA was 20-fold less potent than testosterone, and 10-fold less potent than dexamethasone in binding to the androgen and glucocorticoid cytosolic receptors, respectively. The binding of MPA to progestrone, androgen and glucocorticoid receptors predicted direct effects of MPA on FSH-stimulated estrogen (E), progesterone (P), and 20 alpha-dihydroprogesterone (DHP) production by cultured rat ovarian granulosa cells. MPA at 10(-7) to 10(-6) M significantly augmented FSH-stimulated P and DHP production (a previously documented progestin, androgen and glucocorticoid effect). This augmentation was blocked by the concurrent addition to cell culture of 10-fold excess RU-486 (a potent anti-progestin and anti-glucocorticoid). At concentrations greater than 10(-6) M, MPA inhibited the production of P and DHP (a progestin effect), and the production of E (a progestin and glucocorticoid effect). MPA, structurally a progestin, has complex steroid hormone effects predicted by its interaction with progesterone, androgen and glucocorticoid receptors.

20-alpha-Dihydroprogesterone↗

An evaluation of procedures for assessing competency to stand trial.

In a field experiment involving 120 defendants at Bridgewater State Hospital in Massachusetts, the authors evaluated three instruments for assessing competency to stand trial: the Competency Screening Test (CST), Competency Assessment Instrument (CAI), and Interdisciplinary Fitness Interview (IFI). The CST (a paper-and-pencil test) was administered by a research assistant and scored by trained graduate students. Lawyers, psychologists, and social workers were recruited and trained in the use of the other instruments, then assigned as individuals (CAI) or teams (IFI) to conduct interviews and assess subjects. The performance of the project interviewers was compared against two yardsticks: (1) actual decisions reached by the regular Bridgewater staff, and (2) a consensus of two nationally respected experts who reviewed the cases and formed independent competency judgments. Both the CAI and IFI performed well under these conditions, indicating that one-time interviews by well-trained persons can lead to accurate competency decisions in the majority of cases. The authors conclude that hospitalization for competency assessment is rarely necessary.

Forensic Psychiatry↗

Evidence for a free radical mechanism of styrene-glutathione conjugate formation catalyzed by prostaglandin H synthase and horseradish peroxidase.

We have proposed, using styrene as a model, a new mechanism for the formation of glutathione conjugates that is independent of epoxide formation but dependent on the oxidation of glutathione to a thiyl radical by peroxidases such as prostaglandin H synthase or horseradish peroxidase. The thiyl radical reacts with styrene to yield a carbon-centered radical which subsequently reacts with molecular oxygen to give the styrene-glutathione conjugate. We have used electron spin resonance spin trapping techniques to detect the proposed free radical intermediates. A styrene carbon-centered radical was trapped using the spin traps 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and t-nitrosobutane. The position of the carbon-centered radical was confirmed to be at carbon 7 by the use of specific 2H-labeled styrenes. The addition of the spin trap DMPO inhibited both the utilization of molecular oxygen and the formation of styrene-glutathione conjugates. Under anaerobic conditions additional styrene-glutathione conjugates were formed, one of which was identified by fast atom bombardment mass spectrometry as S-(2-phenyl)ethylglutathione. The glutathione thiyl radical intermediate was observed by spin trapping with DMPO. These results support the proposed free radical-mediated formation of styrene-glutathione conjugates by peroxidase enzymes.

Aminopyrine↗