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Biomedical subjects

C R Brown

Publications and source records attributed to C R Brown.

At least 163 records · Page 9Linked to original sources

A bioassay for a water-soluble benzodiazepine against sodium thiopental.

The authors performed a bioassay of midazolam maleate, an investigational, water-soluble benzodiazepine; to determine the duration of sleep after a single intravenous dose. Sodium thiopental was the standard against which the midazolam maleate was assayed. Prior to operation 60 surgical patients were randomly given one of five doses of drugs, either thiopental, 180 or 270 mg, or midazolam maleate, 6.6, 10, or 15 mg. The designated drug was infused intravenously over 20 sec in a double-blind fashion. Sleep was defined as commencing when the patients stopped counting, and ending when they could respond appropriately to verbal commands. Midazolam maleate, 10 mg (9--12 mg represents 95 per cent confidence limits), was found to be equivalent to thiopental, 200 mg, in the duration of sleep induced. Apnea following the infusion was less frequent and of shorter duration after midazolam maleate than after thiopental. It is concluded that midazolam maleate is a satisfactory agent for the induction of anesthesia, and that it is about 20 times as potent as thiopental.

Adolescent↗

Studies on ram acrosin. Activation of proacrosin accompanying the isolation of acrosin from spermatozoa, and purification of the enzyme by affinity chromatography.

1. A previously described, freeze-dried, partially purified ram acrosin preparation was fractionated on a column of Sepharose linked to the acrosin inhibitor p-(p'-aminophenoxypropoxy)benzamidine. Two acrosin fractions were obtained. 2. beta-Acrosin was homogeneous, quite stable at low pH and very stable when freeze-dried. Its molecular weight is about 38000, and it contains about six sugar residues per molecule, but no sialic acid. psi-Acrosin consisted of at least three unstable forms of acrosin. 3. When the entire purification process, starting from collection of semen, was carried out as rapidly as possible, the yield of beta-acrosin was increased and very little psi-acrosin was obtained. 4. In fresh ram semen the acrosin is present as the intra-acrosomal zymogen, proacrosin. After its extraction from spermatozoa autoproteolytic reactions convert proacrosin into beta-acrosin; psi-acrosin appears to be breakdown products of beta-acrosin. 5. When beta-acrosin was passed through a column of Sepharose linked to the non-inhibitory deamidinated analogue of the inhibitor it behaved as a hydrophobic protein. This is consistent with our view that acrosin (as zymogen) occurs in spermatozoa as a membrane-bound protein. 6. Success in the isolation of pure acrosin in high yield calls for an affinity adsorbent with the appropriate subsidiary hydrophobic properties.

Acrosin↗

The activation of proacrosin in spermatozoa from ram bull and boar.

Acrosin activity was estimated in fractions from washed ram, bull and boar spermatozoa that had been disrupted using a Stansted Cell Disruptor. When p-aminobenzamidine was included in the medium during disruption, all the acrosin (acrosomal proteinase, EC 3.4.21.10) was recovered as its inactive zymogen form, proacrosin. But if spermatozoa were damaged before disruption, of were disrupted in the absence of p-aminobenzamidine, considerable amounts of active acrosin were detectable. It was concluded that conversion of proacrosin to acrosin takes place in spermatozoa only after the acrosome has been rutured. In a sucrose medium, all the proacrosin was bound to the sperm heads. Conversion to acrosin took place readily with all components in a bound state. Using arm sperm heads, the conversion was found to be relatively insensitive to pH, proceeding rapidly above pH 6.5; the rate of conversion was not affected by physiological levels of Ca2+, Mg2+, or Zn2+, although elevated ionic strength caused a solubilization of the acrosin activity and some slowing of the rate. Electrophoretic analysis revealed that several active forms of acrosin were involved, but the final product was a single stable form. Final levels of the active acrosin (expressed as mu mol N-alpha-benzoyl-L-arginine ethyl ester utilised/min per 10(9) heads) were: ram 26.2; bull, 15.9; boar, 133.8. But active site titration revealed that these different levels were not reflected in the numbers of active enzyme molecules on the sperm head; boar acrosin appears to be about three times more active towards benzoyl-arginine ethyl ester than do the acrosins from the other species.

Acrosin↗

Enamel loss during orthodontic bonding and subsequent loss during removal of filled and unfilled adhesives.

1. The techniques required in the removal of highly filled composite adhesives at the end of orthodontic treatment on an average cause more loss of enamel than removal of an unfilled polymethylmethacrylate adhesive. 2. The amount of enamel lost during the removal of either adhesive may be of clinical significance because of the removal of a major part of the protective fluoride-rich layer of enamel. 3. The use of zirconium silicate on a rotating bristle brush may cause considerable abrasion of enamel.

Acid Etching, Dental↗

The use of benzodiazepines in prison populations.

Experience with the use of tranquilizing drugs in the control of anxiety and in attempts at behavior modification, prompted a controlled study in the use of the benzodiazepines at the Utah state prison. It appeared that the benefits derived from the administration of these drugs in prisoner control were nearly outweighed by the frequent appearance of paradoxical rage reactions and increase in hostility and aggressive tendencies in these individuals. A double blind, cohort, prospective, randomized study was set up comparing Valium and Serax in their antianxiety qualities and their tendency to produce increased aggression and paradoxical rage reactions. Guidelines are proposed for the use of benzodiazepines and Serax is suggested as a superior drug to Valium for this purpose if indeed a tranquilizer of this type is indicated.

Aggression↗

Dextroamphetamine with morphine for the treatment of postoperative pain.

In a double-blind, single-dose study, dextroamphetamine combined with morphine was compared with morphine alone to determine the relative efficacy of the combination given intramuscularly for postoperative pain. Each of 450 patients received one treatment of morphine sulfate (3, 6 or 12 mg) with dextroamphetamine (0, 5 or 10 mg). Analgesia, as measured by the patients' subjective responses to questions about relief of pain, was augmented when dextroamphetamine was given with morphine; the combination of dextroamphetamine, 10 mg, with morphine was twice as potent as morphine alone, and the combination with 5 mg was 1 1/2 times as potent as morphine. In simple performance tests, and in measures of side effects, dextroamphetamine generally offset undesirable effects of morphine (sedation and loss of alertness) while increasing analgesia. Effects on blood pressure, pulse and respiratory rate were minimal.

Adult↗

A simple on-line device for scanning photographs.

A cheap scanner, based on an x-y plotter, is described which has a resolution of 128 elements x 128 elements minimum. Digitisings obtained suggest that, at most, 20 grey levels can be resolved.

Computers↗

Assay of aspirin and naproxen analgesia.

To establish the relative potency of naproxen and aspirin for oral analgesia, a 4-point, noncrossover bioassay with placebo control was undertaken with 197 patients. Subjective-response methods were used to determine two measures of postoperative analgesia over a period of 6 hr. With reasonable confidence for an oral analgesic assay, we found 220 mg of naproxen to be equivalent to 600 mg of aspirin for pain relief and 330 mg of naproxen to be equivalent to 600 mg of aspirin for decreased pain intensity.

Administration, Oral↗

Conservatism as a determinant of sexual experiences.

An examination of the relationship of conservatism to reports of sexual experiences and reasons for nonparticipation was conducted using 64 male and 50 female introductory psychology students. Conservatism was found to be inversely related to the frequency and variety of sexual behaviors. High conservative subjects gave the reason that it was morally wrong more often than any other reason for not engaging in coital activities and more intimate forms of petting. Results were in accord with previous research and were interpreted as supporting the notion that the fear of loss of control of one's impulses and hence the basis for conservative attitudes are determinants of sexual experiences.

Attitude↗

Effects of acrosin inhibitors on the soluble and membrane-bound forms of ram acrosin, and a reappraisal of the role of the enzyme in fertilization.

When denuded ram spermatozoa were suspended in weakly buffered 0.25M sucrose, the acrosin remained bound to the acrosomal membranes of the sperm heads. Media containing CaCl2 caused complete solubilization of the enzyme. Effects of acrosin inhibitors on soluble and bound enzyme were studied in Tris HCl(pH 8.2) containing sucrose. Denuded spermatozoa were used as a preparation of bound acrosin. Trasylol (Kunitz basic pancreatic trypsin inhibitor) acted more strongly on bound scrosin than on soluble acrosin, but soya-bean trypsin inhibitor acted more strongly on soluble acrosin. At concentrations 0.5 - 2.0muM, the inhibitors isolated from ram acrosomes and from ram seminal plasma inhibited soluble acrosin but had negligible effects on bound acrosin. However, bound acrosin was sensitive to high concentrations of the acrosomal inhibitor. The two forms of acrosin were inhibited to about the same degree by p-aminobenzamidine and also by Tos-Lys-CH2Cl. It is proposed that membrane-bound acrosin is the form that functions in penetration of the zona pellucida, and that a role for acrosin inhibitors is suppression of an antifertility effect of soluble acrosin on mammalian eggs. This hypothesis is supported by 1) the results of work on the impaired fertilizing capacity of rabbit spermatozoa that have been treated with acrosin inhibitors, 2) the anti-fertility effects on hamster eggs of solutions of acrosin and of bovine trypsin, and 3) the results in this paper.

Acrosin↗

Comparison of neutral proteinase activities in cock and ram spermatozoa and observations on a proacrosin in cock spermatozoa.

Cock spermatozoa, like trypsin, induced a rapid fall in the viscosity of gelatin solutions but ram spermatozoa and inhibitor-free ram acrosin were ineffective. The gelatin-hydrolysing activity in cock spermatozoa was solubilized at pH 8 in the presence of calcium ions but comparable extracts of ram spermatozoa were inactive. Both extracts showed acrosin activity (assayed with benzoylarginine ethyl ester). The two catalytic activities of cock spermatozoa were each susceptible to the same trypsin inhibitors and during fractionations they were not separable. We deduce that cock acrosin, and probably some other avian acrosins, have the power to degrade dissolved gelatin while ram acrosin does not. The acrosin in cock spermatozoa, unlike that in ram spermatozoa, was inactivated at pH 2-7. Acid extracts of the former contain an inactive precursor of acrosin which undergoes spontaneous re-activation in buffers, pH 8, containing calcium ions. In this respect it resembles the proacrosin of rabbit testis.

Acrosin↗

The mandate project: institutionalizing a system of patient care quality assurance.

In 1970, prior to present-day requirements for quality assurance programs, a project was undertaken to institute such a program voluntarily in ten hospitals. Five hospitals succeeded in fully implementing the program which was based on the "Bi-Cycle Process" and each documented improvements in desired patient care behaviors. Two hospitals partially implemented the process and demonstrated no significant changes in desired patient care behaviors. Two hospitals failed to provide the data upon which assessments could be made and one hospital never got beyond preliminary efforts at instituting the process. The project demonstrates that a voluntary quality assurance program is feasible and has important implications for PSROs and continuing medical education. It also provides evidence that attention to psychosocial factors is essential in the institutionalization of programs designed to produce desired changes in patient care behaviors.

Education, Medical, Continuing↗

Hypnotic efficacy of diphenhydramine, methapyrilene, and pentobarbital.

The antihistamines diphenhydramine and methapyrilene were compared with pentobarbital for hypnotic effect in two Veterans Administration Hospital populations using subjective-response methods. In the first part of the study, 60 mg and 180 mg of pentobarbital were compared with 50 mg and 150 mg of diphenhydramine. A positive dose-response relationship was obtained only for pentobarbital; neither dose of diphenhydramine was significantly different from 60 mg of pentobarbital for any response variable. In the second part of the study, 100 mg of pentobarbital, 50 mg of diphenhydramine, and 50 mg of diphenhydramine, and 50 mg of methapyrilene were compared with placebo. One hundred mg of pentobarbital and 50 mg of diphenhydramine were significantly different from placebo, but 50 mg of methapyrilene was not.

Adult↗