Mutagenesis of the glycerol dehydrogenase from Bacillus stearothermophilus.
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Amino Acid Sequence↗
Biomedical subjects
R Burton
Publications and source records attributed to R Burton.
Withdrawing antihypertensive treatment.
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Humans↗
Tamoxifen and partial oestrogen agonism in postmenopausal women.
The effect of tamoxifen on the vaginal mucosa and on serum oestrone, oestradiol and gonadotrophin concentrations was investigated in a group of nine postmenopausal women with non-metastatic breast cancer. Compared with fit age-matched controls, the vaginal pH in the tamoxifen-treated group was significantly lower and was comparable to levels in fertile women. Two thirds of tamoxifen-treated women had well oestrogenized vaginal smears compared with none in the control group. Follicle-stimulating hormone was significantly reduced, whilst oestrone and oestradiol levels remained unchanged. We conclude, therefore, that tamoxifen has oestrogen-agonistic properties particularly evident in postmenopausal women, even though it is primarily an antioestrogenic drug.
Aged↗
Cost offset from a psychiatric consultation-liaison intervention with elderly hip fracture patients.
OBJECTIVE: The authors hypothesized that psychiatric liaison screening of elderly patients with hip fractures would shorten the average length of hospital stay and increase the proportion of patients who returned home after discharge. METHOD: The study was performed at Mount Sinai Medical Center in New York and Northwestern Memorial Hospital in Chicago. The subjects were 452 patients 65 years or older who were consecutively admitted for surgical repair of fractured hips. During a baseline year the patients received traditional referral for psychiatric consultation. During the experimental year all the patients at Mount Sinai and the patients on one Northwestern Unit were screened for psychiatric consultation. RESULTS: The patients who received psychiatric liaison screening had a higher consultation rate than those who received traditional consultation. The rates of DSM-III disorders in the experimental year were 56% at Mount Sinai and 60% at Northwestern. The mean length of stay was reduced from 20.7 to 18.5 days at Mount Sinai and from 15.5 to 13.8 days at Northwestern, resulting in reductions in hospital costs ($647/day) of $166,926 and $97,361, respectively. Fees generated from Medicare service delivery could have paid for the $20,000 psychiatric intervention cost at each site. There was no difference, however, between the two years in the discharge placement of patients. CONCLUSIONS: Admission psychiatric liaison screening of elderly patients with hip fractures results in early detection of psychiatric morbidity, better psychiatric care, earlier discharge, and substantial cost savings to the hospital.
Aged↗
Emergency contraception.
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Contraceptives, Postcoital↗
Possible impairment of the sympathetic nervous system response to postprandial hypotension in elderly hypertensive patients.
In a randomised, single-blind, cross-over study, the effects of a high carbohydrate meal or 'no meal' on BP, pulse rate, blood glucose, plasma insulin and catecholamine levels were assessed in eight fit, untreated, elderly hypertensive subjects. A significantly greater fall in supine (P = 0.006) and erect (P = 0.03) systolic blood pressure (SBP) occurred post-meal compared with the no meal phase. The maximum postprandial fall in supine SBP (-24 mmHg, 95% CI -16 to -32 mmHg) occurred at 60 minutes and was associated with a significant rise in supine pulse rate. No overall difference in diastolic BP was seen between the two phases and orthostatic control of BP was maintained. Blood glucose and plasma insulin levels rose after the meal but plasma noradrenaline levels were unchanged during both phases. Thus in these elderly hypertensive subjects the postprandial fall in SBP was not associated with an overall increase in sympathetic nervous system (SNS) activity (as gauged by plasma noradrenaline levels), unlike the findings previously reported in normotensive elderly and young subjects. These changes in BP and the possible impairment of the SNS response to postprandial hypotension should be considered when assessing the BP control, particularly after therapeutic intervention, in elderly hypertensive patients.
Aged↗
Identification of the biliary metabolites of (+/-)-3-dimethylamino-1,1-diphenylbutane HCl (recipavrin) in rats.
1. The in vivo biliary metabolites of (+/-)-3-dimethylamino-1,1-diphenylbutane hydrochloride (recipavrin) isolated from Wistar rats have been characterized by g.l.c.-mass spectrometry. 2. Non-conjugated metabolites include recipavrin (1), norrecipavrin (2), diphenylbutanone (3), diphenylbutanone oxime (4), diphenylbutanone phenol (12), diphenylbutanone oxime phenol (14), recipavrin phenol (19), diphenylbutanone O-methylcatechol (16) and diphenylbutanone oxime O-methylcatechol (18). 3. Following beta-glucuronidase hydrolysis and extraction from pH 10 solution, diphenylbutanone (3), diphenylbutanone oxime (4), an unidentified compound (6), primary amine (8), norrecipavrin (2), recipavrin (1), phenols (12, 14, 15), norrecipavrin phenol (13), O-methylcatechols (16, 18), diphenylbutanol O-methylcatechol (17), recipavrin O-methylcatechol (19) and a secondary formamide (5) were identified by g.l.c.-mass spectrometry. 4. Various extraction solvents were employed in sample workup. The formamide (5) was present regardless of solvent used, while the trace presence of secondary acetamide (7) may be associated with the use of ethyl acetate. 5. Metabolites isolated after beta-glucuronidase hydrolysis were characterized by g.l.c.-mass spectrometry of the underivatized form, and as the trimethylsilyl (TMS) derivatives, or following methylation with diazomethane or trimethylanilinium hydroxide (TMAH).
Animals↗
Knowledge and use of postcoital contraception: a survey among health professionals in Tower Hamlets.
The knowledge and estimated retrospective use of postcoital contraception was ascertained from health professionals in Tower Hamlets in the summer of 1988 using a postal questionnaire. Eighty five per cent of general practitioners responded and 91% of these had received requests for postcoital contraception within the previous six months. Only one third of general practitioners had information about postcoital contraception available in their surgeries. Family planning doctors and nurses had the most accurate knowledge of the method but many health professionals appeared to lack sufficient knowledge to ensure appropriate prescribing and to publicize this method to their women patients. It is concluded that if the high rate of abortion in the borough is to be reduced, health professionals as well as women need to be further educated as part of a postcoital contraception publicity campaign. Use of the term 'emergency contraception' rather than the non-medical term 'the morning after pill' may be more effective and reduce the present confusion among both groups.
Adult↗
Negative ion chemical ionization gas chromatography/mass spectrometry of valproic acid metabolites.
A negative ion chemical ionization (NICI) gas chromatographic/mass spectrometric method is described for the identification of 15 valproic acid (VPA) metabolites as their pentafluorobenzyl derivatives. Samples analyzed were serum, urine and saliva taken from a volunteer on VPA at steady state and also given selected doses of (2H6)VPA. Metabolite peaks were identified by comparison to synthetic standards. All the metabolites, like the parent drug, produced abundant [M - 181]- ions, except 3-keto VPA, which gave an [M - 181 - CO2]- ion. Using the NICI method, two new VPA metabolites were identified. One of these metabolites was characterized as 4'-keto-2-ene VPA by synthesis, while the second one appeared to be a positional isomer of 4'-keto-2-ene VPA. The sensitivity of the method was also sufficient to detect metabolites of VPA in saliva. The ratio of the levels of (Z)-2-ene VPA to (E)-2-ene VPA was much greater in saliva than in serum, suggesting stereoselective plasma protein binding or transport of these two metabolites. The lower limit of detection for the quantification of VPA in serum or saliva was 2 ng ml-1.
Biotransformation↗
A staging system for mouse limb development.
A series of 15 stages of development for the mouse limb bud have been defined, spanning the time from the first appearance of the limb bud to the completion of limb outgrowth. The stages are based on changes in the morphology of the limb in living preparations. The development and regression of the apical ectodermal ridge (AER) as well as the development of the skeletal structures are also described. This staging system has been developed in response to the need to standardize in situ experimental analyses of the mouse limb bud. Comparable stages of the commonly used chick wing and mouse whole embryo systems are presented.
Animals↗
A simple microcomputer interface for tail-flick determination.
An inexpensive means of tail-flick latency data acquisition and analysis using an Apple IIe microcomputer and three simple interface circuits is described. Descriptions of the software and hardware are provided with schematics and program listings. The measurement, storage, and analysis of the data are integrated in one system.
Animals↗
In vitro functional reactivities of cutaneous mast cells from patients with mastocytosis.
Cutaneous mast cells from 3 patients with mastocytosis were evaluated for their morphologic characteristics and in vitro functional reactivities to different secretory agonists. By electron microscopy, mastocytosis mast cells appeared larger than normal skin mast cells, frequently had atypical, highly indented or bilobed nuclei, and each contained numerous, elongated cytoplasmic projections. Suspensions of mastocytosis mast cells were obtained from lesional skin biopsy specimens, and their response to both immunologic and nonimmunologic secretagogues was compared with mast cells from normal skin. Lesional skin mast cells had a net histamine release of 12.3% (+/- 1.3 SEM) and 31.1% (+/- 6.0 SEM) following stimulation with the purified human anaphylotoxin C3a and mouse monoclonal antihuman IgE antibodies, respectively. This specific release was similar to the responses observed in normal skin mast cells (11.5% +/- 4.5 SEM and 16.7% +/- 2.1 SEM, respectively). Mast cells from cutaneous lesions of mastocytosis also responded to the nonimmunologic secretagogues, morphine sulfate and calcium ionophore A23187 with a specific histamine release of 15.1% (+/- 1.2 SEM) and 39.8% (+/- 8.7 SEM), respectively. The results of this study demonstrate that mast cells from lesions of mastocytosis are morphologically atypical, but have a histamine content similar to normal skin mast cells and retain their functional reactivities to clinically relevant secretory stimuli.
Child↗
The influence of age and gender on normal appendicectomy rates.
Epidemiological data from a retrospective analysis of 1307 pathology reports of appendicectomy specimens from four Hunter Valley Hospitals, having a 100% tissue audit, showed that there was a significant difference in normal appendicectomy (histologically normal appendix following appendicectomy for suspected acute appendicitis) rates for the young (male and female 0-12 years) and reproductive female (13-50 years) groups when compared with the elderly (over 60 years) and the rest (male 13-59, female 51-59 years) of the population. The overall normal appendicectomy rate was 26%, and the perforation rate 3.6%. These data suggest that suspected acute appendicitis in the Hunter Valley is managed in an appropriate way. The perforation rate was significantly higher in the elderly group, and management of these patients will remain a problem due to delayed and atypical presentation. Continuing audit programmes and area-wide review should contribute to improved accuracy in the diagnosis of acute appendicitis.
Adolescent↗
Capillary gas chromatography-mass spectrometry of valproic acid metabolites in serum and urine using tert.-butyldimethylsilyl derivatives.
A quantitative method has been developed for valproic acid and twelve of its metabolites using capillary gas chromatography--mass spectrometry with selected-ion monitoring. The method is applicable to serum or urine and all metabolites are measured in a single run. Ions selected for quantitative purposes were the characteristic (M-57)+ ions of the tert.-butyldimethylsilyl (tBDMS) derivatives. The 4-hydroxyvalproic acid was measured as the gamma-lactone. Calibration curves were found to be linear and the sensitivities in the order of 0.1 microgram/ml. Patient data are presented. A comparison of tBDMS and trimethylsilyl (TMS) derivatives showed that tBDMS gave superior sensitivity for the unsaturated metabolites and a shorter analysis time. Mixed tBDMS-TMS derivatives were also investigated.
Gas Chromatography-Mass Spectrometry↗
The regeneration of double dorsal and double ventral limbs in the axolotl.
Surgically made double dorsal and double ventral upper arms, comprising double extensor and double flexor muscles respectively, were amputated immediately following operation; both limb types regenerated. In terms of skeletal anatomy, a range of limb types was found. These included four-digit limbs of normal cartilage pattern, and hypomorphic limbs having from one to three digits. All of the double dorsal and the majority of the double ventral limbs were symmetrical in the dorsal-ventral axis. This was detected by analysing their muscle patterns at carpal and mid-forearm level, and muscle and epidermal characteristics in the metacarpal region are discussed in terms of the significance of healing time and stump pattern on the regenerative ability of surgically created limb regions.
Ambystoma↗
Methadone metabolism in the rat in vivo: identification of a novel formamide metabolite.
Deuterium-labelled methadone and metabolites were used for the g.l.c.-mass spectrometry detection and identification of biliary conjugated methadone metabolites in rats. After beta-glucuronidase hydrolysis the bile extract contained an unknown metabolite that was not ring hydroxylated and retained an intact keto group. Chemical oxidation of the methadone metabolite 2-ethylidene-N,5-dimethyl-3,3-diphenylpyrrolidine, perchlorate salt (EDDP) with m-chloroperbenzoic acid in chloroform, gave a compound identical by g.l.c.-mass spectrometry to the new metabolite. The chemical oxidation product was identified as 2-(4',4'-diphenylheptan-5'-one-2'-yl)oxaziridine by spectroscopic methods. The oxaziridine was shown to quantitatively isomerize to a secondary formamide (2-formamido-4,4-diphenyl-5-heptanone) during g.l.c.-mass spectrometry analysis. The formamide was also isolated by flash column chromatography after reflux of the oxaziridine in m-xylene, and then characterized by spectroscopy. The formamide and oxaziridine g.l.c.-mass spectrometry characteristics were identical. It was concluded on the basis of g.l.c.-mass spectrometry that the metabolite is the secondary formamide.
Animals↗
The use of ophthalmosonometry in the diagnosis of carotid artery stenosis.
One hundred and fifty-two patients underwent supraorbital Doppler studies of 304 carotid arteries to determine the presence or absence of hemodynamically significant lesions. Subsequent carotid arteriography was used to validate the accuracy of the test. Of 124 patients having abnormal Doppler examinations, 107 (86%) were angiographically proved to have lesions of the internal carotid artery that produced a stenosis of 50% or more. In the last 80 patients, the accuracy was increased to 94%. Of 115 proved stenoses or occlusions, the supraorbital Doppler examination correctly identified 99, for a diagnostic accuracy of 86%. In the last 50 patients, this accuracy was increased to 93%. Since only 58% of the patients with lesions had a bruit, the Doppler study was of particular value in identifying the patients with significant lesions in the absence of a bruit. Likewise, since only 61% of carotid arteries with bruits had lesions of hemodynamic significance, a normal Doppler examination could have been used to avoid angiographic screening of those arteries with bruits in the absence of major lesions, providing those hemodynamically insignificant lesions were not producing symptoms related to emboli. The technique of ophthalmosonometry and the significance of the test in clinical evaluation is discussed.
Blood Flow Velocity↗
Latency of some glycosidases of rat liver lysosomes.
The latency of the alpha-glucosidase activity of intact rat liver lysosomes was studied by using four substrates (glycogen, maltose, p-nitrophenyl, alpha-glucoside, alpha-fluoroglucoside) at a range of substrate concentrations. The results indicate that the entire lysosome population is impermeable to glycogen and maltose, but a proportion of lysosomes are permeable to alpha-fluoroglucoside and a still higher proportion permeable to p-nitrophenyl alpha-glucoside. Incubation at 37 degrees C in an osmotically protected buffer of of pH 5.0 caused lysosomes to become permeable to previously impermeant substrates and ultimately to release their alpha-glucosidase into the medium. The latencies of lysosomal beta-glucosidase and beta-galactosidase were examined by using p-nitrophenyl beta-glucoside and beta-galactoside as substrates. The results indicate permeability properties to these substrates similar to that to p-nitrophenyl alpha-glucoside. On incubation in an osmotically protected buffer of pH 5, lysosomes progressively released their beta-galactosidase in soluble form, but beta-glucosidase remained attached to sedimentable material. Lysosomal beta-glucosidase was inhibited by 0.1% Triton X-100; alpha-glucosidase and beta-galactosidase were not inhibited.
Animals↗