Biomedical subjects
J Kelly
Publications and source records attributed to J Kelly.
Obstetrics in developing countries.
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Comparison of liquid-junction and coaxial interfaces for capillary electrophoresis-mass spectrometry with application to compounds of concern to the aquaculture industry.
The application of capillary electrophoresis-mass spectrometry (CE-MS) to the analysis of compounds of concern to the aquaculture industry is reported. Two different approaches to coupling the CE column to an IonSpray atmospheric pressure ionization (API) interface, viz., a liquid-junction and a coaxial arrangement, are describe and compared with regard to ruggedness, ease of use, sensitivity and electrophoretic performance. The different injection modes used in three commercial capillary electrophoresis systems were also evaluated for their applicability to CE-MS. The use of CE-MS for the analysis of a variety of classes of antibiotics used in the fish aquaculture industry, such as the sulfonamides and their potentiators (e.g., trimethoprim), is demonstrated and was used to confirm the presence of these components in shellfish extracts at the low ppm level. CE-MS was also applied to the analysis of marine toxins such as saxitoxin and its analogues which are associated with paralytic shellfish poisoning, and also the toxins responsible for amnesic and diarrheic shellfish poisoning. Tandem mass spectrometry (MS-MS) was used to provide structural information on these analytes, and the ability to distinguish isomeric compounds based on their different migration and fragmentation characteristics using CE-MS-MS is demonstrated.
Determination of erythromycin A in salmon tissue by liquid chromatography with ion-spray mass spectrometry.
A reverse-phase liquid chromatography/mass spectrometry (LC/MS) method, incorporating gradient elution, is described for the characterization of residual erythromycin A and its metabolites in salmon tissue. The method uses ion-spray, a mild atmospheric pressure ionization technique which provides an abundant protonated molecule well suited for selected ion monitoring experiments. Tandem mass spectrometry (MS/MS) using collision-induced dissociation was used to provide structural information. The LC/MS method was tested for the analysis of salmon tissue spiked with erythromycin A at levels between 0.01 and 1 p.p.m. A simple extraction and clean-up procedure, slightly modified from that described by Takatsuki et al. (J. Assoc. Off. Anal. Chem. 70, 708 (1987)), was used in this work. Using selected ion and selected reaction monitoring techniques, the LC/MS and LC/MS/MS methods provided detection limits of < 10 and 50 ng g-1, respectively. Confirmatory full-scan LC/MS and LC/MS/MS spectra were obtained at the 0.5 and 1 microgram g-1 levels, respectively. Using a combination of these techniques, the presence of residual erythromycin A was confirmed in the tissue of fish administered medicated feed containing the antibiotic. In addition, several metabolites and degradation products of erythromycin A, including anhydro-erythromycin and N-demethyl-erythromycin, were detected and where possible confirmed by comparison with authentic compounds. Although this analytical method has been shown to afford the necessary sensitivity and precision, application of these techniques to high-throughput quantitative analyses will require development of an improved clean-up procedure and preferably also of a suitable surrogate internal standard.
SK&F 104078, a post-junctionally selective alpha 2-adrenoceptor antagonist in the human saphenous vein in vitro.
The present study investigated the effects of SK&F 104078 (6-chloro-9-[(3-methyl-2-butenyl)oxy]-3-methyl-1H,2,3,4,- tetrahydro-3-benzazapine) at pre- and post-junctional alpha 2-adrenoceptors in the human isolated saphenous vein. Noradrenaline (0.001-100 mumol/l) produced concentration-dependent contractions of the human saphenous vein which were competitively antagonised by the alpha 1-adrenoceptor antagonist prazosin (0.01-1.0 mumol/l) and the alpha 2-adrenoceptor antagonist, rauwolscine (0.01-1.0 mumol/l), indicating the presence of both post-junctional alpha 1- and alpha 2-adrenoceptors in this preparation. The selective alpha 2-adrenoceptor agonist, UK-14,304 (0.01-100 mumol/l) also produced concentration-dependent contractions of the human saphenous vein which were antagonised by both rauwolscine (0.1 mumol/l) and prazosin (0.1 mumol/l). In the presence of angiotensin II (0.05 mumol/l), which itself produced a transient contraction, rauwolscine (0.1 mumol/l) produced a rightward shift of the UK-14,304 concentration-response curve while prazosin (0.1 mumol/l) had no effect. SK&F 104078 (10.0 mumol/l) under these conditions also produced a rightward shift of the concentration-response curve to UK-14,304, but was at least 100-fold less potent than rauwolscine. At pre-junctional alpha 2-adrenoceptors, exogenous noradrenaline (0.01 and 0.1 mumol/l) induced a concentration-dependent inhibition of stimulation-evoked [7-3H]-noradrenaline release from the human saphenous vein in vitro, which was antagonised by rauwolscine (0.1 mumol/l) and tolazoline (10.0 mumol/l) but not by SK&F 104078 (10.0 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative morphometric study of muscle in inclusion body myositis.
Clinical and electromyographic findings do not clearly distinguish inclusion body myositis (IBM) from chronic polymyositis (PM). The rimmed vacuoles and filamentous nuclear and cytoplasmic inclusions that characterize IBM are often sparse and may be overlooked; conversely, these features may occasionally be seen in other diseases. Preliminary studies suggested that muscle fiber hypertrophy occurred more frequently in IBM than in PM. To investigate whether fiber hypertrophy can be used to improve the ability to separate IBM from PM, we report a morphometric analysis of 28 IBM cases, 22 PM and 22 dermatomyositis (DM) cases. The analysis, using a computer automated system, included proportion of hypertrophied fibers and also fiber type proportions, average fiber diameter, proportion of atrophic and angulated fibers, and the co-dispersion index (CDI). The proportion of hypertrophied fibers was greater in IBM than the other two conditions (IBM (mean +/- SEM) 31.0 +/- 4.7% and 12.2 +/- 2.4% for type 1 and type 2 fibers, respectively, compared to 9.8 +/- 3.0% and 3.3 +/- 1.7% in PM, and 7.7 +/- 2.7% and 3.9 +/- 1.9% in DM). These differences were statistically significant (P < 0.05) in both sexes for type 1 fibers and in women for type 2 fibers. Also, the average fiber size and hypertrophy factors for type 1 and type 2 fibers were increased in IBM compared to PM and DM. This study confirms that the presence of muscle fiber hypertrophy in biopsies from IBM patients may help differentiate them from other clinically similar inflammatory myopathies.
Peribulbar anaesthesia: failure to abolish the oculocardiac reflex.
Peribulbar anaesthesia is a form of regional anaesthesia which has been used with increasing popularity in cataract surgery. Recently indications for its use have been extended to include surgery for vitreo-retinal disease and strabismus. This study shows that in nine of 11 patients in whom the oculocardiac reflex was stimulated by traction on an extra-ocular muscle, peribulbar anaesthesia failed to abolish the reflex. In each of these patients, the reflex manifested as a bradycardia. In one subject, the bradycardia was profound, showing no QRS complex for five seconds. We recommend that cardiac rhythm be monitored throughout procedures performed under peribulbar anaesthesia, and that a vagolytic agent be available for immediate use.
Audit of health services in Gurage.
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Vesico-vaginal and recto-vaginal fistulae.
A personal series of 716 patients with vesico-vaginal and/or recto-vaginal fistulae is presented. Five hundred and seventy-eight patients were managed in Africa, mainly at the Addis Ababa Fistula Hospital, while 138 were kindly referred to me from various parts of Britain. The main cause of such fistulae in the developing world is pressure necrosis from obstructed labour. In the developed world the aetiology is surgery, malignancy, radiotherapy or a combination of these. Other causes include neglected foreign bodies, coital injury and local treatment by an unqualified practitioner. A vesico-vaginal fistula alone was present in 78.8%, a recto-vaginal fistula alone in 4.3%, while 16.9% of patients had both a vesico-vaginal and a recto-vaginal fistula. Six hundred and six (84.6%) patients were cured at the first attempt at repair, 45 (6.3%) failed and 65 (9.1%) had stress incontinence.
Bioquest Limited.
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Pseudogout, chondrocalcinosis and the early recognition of haemochromatosis.
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Capture of chromosomal DNA by anti-histone antibodies for PCR.
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The uaY positive control gene of Aspergillus nidulans: fine structure, isolation of constitutive mutants and reversion patterns.
The product of the uaY gene of Aspergillus nidulans is necessary for the expression of at least eight genes coding for enzymes and permeases of the purine utilisation pathway. A detailed fine structure map has been constructed of this gene involving 13 presumed point mutations and eight deletions. Gene conversion of these deletions was demonstrated. A technique was devised to select for constitutive mutations and two were obtained which map within the uaY gene. We have shown that the most centromere proximal allele reverts to a number of different phenotypes. The properties of this allele suggest that it may map in the open reading frame of the uaY gene, in a domain that could be altered in a way that would differentially affect the expression of genes under uaY control.
Clinical benefits of structural and functional changes with calcium antagonists.
Calcium antagonists have a large variety of pharmacologic effects in addition to those exploited clinically. All drugs used in the management of hypertension, including calcium antagonists, are coming under increasing scrutiny for the possible beneficial and adverse effects they may have on the circulation and risk factor profile. This is particularly because of concern about the relative resistance of coronary heart disease to antihypertensive drug treatment and the increasing interest in evaluating the impact of blood pressure-lowering drugs on surrogate endpoints such as left ventricular hypertrophy. Given the pharmacokinetic and pharmacodynamic heterogeneity of calcium antagonists, it may be wise to keep in mind the subtypes as exemplified by the prototypes nifedipine, diltiazem, and verapamil and to extrapolate from one type to another with great caution. The increased understanding of the diversity among calcium antagonists as well as the pathophysiology of hypertension and other vascular diseases promises an exciting future for calcium antagonists in cardiovascular therapeutics.
Fistulae of obstetric origin.
World Health Organization (WHO) estimates that in the developing countries 5 million women each year suffer severe maternal morbidity and high on this list is obstetric fistulae (vesico-vaginal and/or recto-vaginal). This article tries to explain why these fistulae still occur, comments on measures of prevention and how treatment might best be provided for those women who suffer from this terrible affliction.
Anti-platelet antibodies: a prognostic marker in pregnancies associated with lupus nephritis. Case reports.
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Effects of Yersinia enterocolitica infection on rabbit intestinal and colonic goblet cells and mucin: morphometrics, histochemistry, and biochemistry.
The effects of Yersinia enterocolitica on intestinal goblet cells were investigated in New Zealand white rabbits. Animals infected with Y enterocolitica were compared with weight matched and pair fed controls. Goblet cell hyperplasia developed in the distal small intestine of infected rabbits on day 1, in the mid small intestine on day 3, and in the upper small intestine on day 6. In all regions hyperplasia persisted throughout the 14 day study. The degree of hyperplasia was greater in the distal small intestine than the upper and mid regions. Goblet cells in the proximal colon of infected animals seemed to respond as those in the distal small intestine. Thus goblet cell hyperplasia developed more rapidly and to a greater extent in the ileocaecal region where mucosal injury was most severe. These changes resulted directly from Y enterocolitica infection since goblet cell numbers did not increase in pair fed controls. Histochemically, goblet cell mucins from infected rabbits were unchanged at either six or 14 days. Biochemical analysis, however, established that purified mucins from animals on day 6 after infection were less sialylated (in the small intestine) and more sulphated (in the small intestine and proximal colon). In addition, mucins from the distal small intestine and the proximal colon seemed to contain fewer but longer oligosaccharide chains.
The areas of various surfaces in the human mouth from nine years to adulthood.
Surface area measurements of five regions of the oral cavity were made from study casts of 57 subjects with an age range from 9.3 to 19 years. While the longitudinal pattern of growth exhibited by the total of the five areas, when subgroups were compared, was characterized by a steady increase to around puberty (13 years), followed by a plateau, different areas showed different patterns of growth. Increase in the surface area of the teeth was associated with the eruption of the second and third molars, whereas the area of the buccal lingual mucosa continued to increase into adult life. The palate, buccal vestibular mucosa, and dorsum of the tongue demonstrated a typically skeletal pattern of growth, i.e., increase until puberty with a rapid cessation thereafter. The results of this study indicate the need for longitudinal data to further knowledge concerning growth of the oral cavity.