Kingella kingae orbital cellulitis in a 3-year-old.
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Biomedical subjects
Publications and source records attributed to B Carey.
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The problem of antibiotic resistance is associated with the indiscriminate usage of antibiotics. Efforts have been directed at encouraging the rational use of these drugs to reduce the volume of antibiotic consumption and decrease resistance rates. There is evidence to suggest that the misuse of antibiotics by patients may also contribute to the problem. We describe a survey of a random selection of patients attending a General Practitioners' surgery over a six week period in an effort to estimate the level of non-compliance to antibiotic therapy in the community. The results suggest that there may be a significant level of antibiotic misuse prevalent in the local community. We discuss these results and present evidence in the literature suggesting how antibiotic misuse may affect resistance in the community. The factors affecting patient compliance to therapy are outlined along with suggested measures to improve compliance among patients.
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Members of the steroid/hormone nuclear receptor superfamily regulate target gene transcription via recognition and association with specific cis-acting sequences of DNA, called hormone response elements (HREs). The identification of novel HREs is fundamental to understanding the physiological function of nuclear receptor-mediated signalling pathways. A number of these receptors are transcriptionally active, or can be induced to an active state, when expressed in the yeast strain Saccharomyces cerevisiae. This aspect of nuclear receptor activity was used to screen random rat genomic DNA fragments for their ability to function as a HRE for the farnesoid X-activated receptor (FXR). An isolated genomic fragment mediated FXR transcriptional activation without the co-expression of the retinoid-X receptor (RXR), a receptor previously thought to be an obligate heterodimer partner for FXR function. This genomic sequence of DNA contained a pair of highly conserved HRE half-sites arranged in an everted orientation and separated by 3 bp (ER3). Furthermore, it was located 240 bp from a highly conserved TATA box motif. A minimal ER3 sequence of DNA was further demonstrated to function as a FXR HRE and was bound in vitro by FXR-expressing yeast extracts. Using RT-PCR, an expressed mRNA fragment was identified within an 8 kb region downstream of the putative TATA box motif. This sequence of DNA was observed to bear homology to a cDNA found in mouse blastocyst. These findings define a novel FXR DNA binding specificity but, more importantly, these data suggest that this strategy might be universally applied to any transcription system that can be reconstituted in yeast.
Bollgard cotton is the trademark given to a number of varieties of cotton bio-engineered to produce an insecticidal protein from Bacillus thuringiensis (Bt). When produced by the modified cotton plants, this protein controls certain lepidopterous cotton insect pests. Commercially available since 1996, these cotton varieties are purchased under a license agreement in which the growers pay a fee and agree to abide by the terms, which include a 1-year license to use the technology and agreement to participate in an insect resistance management program. Today, Bollgard cotton is grown on more than one-third of all cotton acreage in the USA. This product has reduced cotton production costs and insecticide use by providing an effective alternative to chemical insecticides for the control of tobacco budworm, Heliothis virescens; cotton bollworm, Helicoverpa zea; and pink bollworm, Pectinophora gossypiella. The specificity and safety profile of the Bt protein produced in planta in cotton was maintained. It has retained its selectivity for lepidopterous insects and lacks the characteristics found in potential allergenic proteins. Fiber quality, the agronomic characteristics of the plant and seed composition remain unchanged. New cotton technology is being developed to provide improved insect control and a wider spectrum of activity. These future products could further reduce insecticide use in the production of cotton, while maintaining the high level of safety and reliability that has been demonstrated by five seasons of Bollgard cotton use.
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Our objective was to review the Australasian experience of X-linked adrenoleukodystrophy (ALD), to compare the spectrum of disease seen in Australasia with previously published data from elsewhere, and to assess the reliability of carrier testing. Study design was a retrospective review of records collected over a 15-year period, the setting was an international referral laboratory for the study of metabolic disease, and the subjects were all known cases of ALD diagnosed in Australia and New Zealand between 1981 and 1996 and their families. We estimate that the combined incidence of ALD and its variants in Australasia is at least 1.6 per 100,000. Of 95 affected males, 51 had cerebral adrenoleukodystrophy, 24 had adrenomyeloneuropathy, 15 had Addison's disease only, and 5 remained asymptomatic when last examined. However, the distribution of phenotypes among newly diagnosed patients has changed substantially over the last 15 years, with cerebral forms of the disease forming a decreasing proportion of new diagnoses. The measurement of plasma very long chain fatty acids (VLCFAs) alone detects 93% of women who can be proven to be carriers. The addition of genetic linkage studies or assay of VLCFAs in cultured fibroblasts improved this detection rate to the point that there were no obligate carriers who could not be detected using a combination of two or more techniques.
In order to examine communication of radiological information under circumstances where rapid exchange of information was essential, we studied communication of non-routine portable chest radiographs to an intensive-care unit (ICU). Images and reports were available through the usual communication channels and through a PACS workstation in the ICU. Data were obtained to determine how quickly and by what means ICU physicians first viewed images and received radiologists' reports of chest radiographs. Peak information demand occurred within 4 h of the examination. The most rapid means of communication was for the physician to visit the radiology department. Image viewing and report receipt were tightly coupled, usually for images which were first viewed as hard copy. PACS performance suffered from unreliable film digitization and delayed report transcription. Integration of computed radiography and digital dictation into a PACS could markedly reduce the delays in ICU physicians' access to radiological information.
RNA blots of total cellular RNA isolated from quiescent and endothelin (ET-1)-stimulated normal rat kidney (NRK) cells demonstrated that ET-1 induced the expression of c-jun, jun B, and c-fos mRNA in a time-dependent manner with maximal expression of mRNA by 1 hr after the addition of ET-1. Five hundred picomolar ET-1 was sufficient to induce maximal mRNA expression. These data agreed with saturation experiments which demonstrated that maximal binding of [125I]ET-1 was achieved at concentrations greater than 100 pM. The Kd and Bmax values for [125I]ET-1 binding to NRK membranes were 20.5 pM and 22.2 fmol/mg protein, respectively. Competition experiments for the binding of [125I]ET-1 to NRK membranes demonstrated that ET-1 was a more potent inhibitor (Ki = 0.047 nM) than ET-3 (Ki = 10.8 nM). No specific binding of [125I]ET-3 (40 or 500 pM) to NRK membranes could be observed. The expression of c-jun, jun B, and c-fos mRNA was inhibited by the endothelin type A receptor (ET)-selective antagonist, BQ-123. Thus, these data demonstrate that ET-1 mediates the expression of immediate response gene mRNA in NRK cells via the ETA receptor. ET-1 stimulation of NRK cells also upregulated EGF receptors, providing a possible mechanism for ET-1 complementation of epidermal growth factor (EGF) mitogenicity in NRK cells.
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Three patients are described with different phenotypes and differing de novo interstitial deletions of the long arm of a chromosome 7. The first patient has a deletion with loss of the proximal 7q11.23 band. Only three other cases have been reported with this particular deletion. Our second case shows mild dysmorphism similar to the other four patients reported with deletion of bands 7q21.12----21.3. Our third patient has a deletion of the 7q22.1----32.2 segment and has many of the phenotypic features of the other reported cases of del 7q22----32. GUSB, the gene for beta-glucuronidase, has been localised to the 7cen----q22 region. Analysis of beta-glucuronidase levels in blood leucocytes of our patients has helped more precisely to assign this gene locus to 7q21.11 or 7q22.1.
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Darodipine is a new light stable dihydropyridine calcium antagonist. In isolated large conductance vessels from experimental animals, darodipine blocks the potential-dependent but not the receptor-operated calcium channel. We studied the effects of darodipine in isolated human epicardial coronary arteries and in isolated right ventricular trabecula obtained from the explanted hearts of patients undergoing cardiac transplantation. In the coronary artery, the PD'2 for calcium was 9.7 and for carbachol was 9.5. In the cardiac muscle, the PD'2 for calcium was 6.5. Using 45Ca2+, darodipine blocked uptake in presence of potassium and histamine. We conclude that darodipine is (1) a potent calcium antagonist in the isolated human coronary artery, but not in ventricular myocardium, thus showing very pronounced target tissue selectivity, and (2) in contrast to findings obtained in rabbit aorta, it inhibits contraction and 45Ca2+ uptake mediated by both the potential-dependent and receptor-operated channels in the human epicardial coronary artery.
Thirty-seven patients admitted consecutively to the Gastroenterology Unit with haemorrhage from oesophageal varices were treated by injection sclerotherapy. The patients were subdivided according to age at presentation (below 65, over 65 years). The mortality and morbidity of the two groups, over the period of follow-up (mean 5.1 months) were compared. The risk of rebleeding was higher in the elderly (0.23 overall) than in the young (0.11 overall) and was reflected in the higher mortality, four of 14 elderly patients and four of 23 younger patients. A further three elderly patients succumbed to intercurrent illness during the same period. In three of the surviving elderly, complete resolution of varices was noted. Complications of sclerotherapy occurred in eight out of 51 injections in the elderly and six out of 97 in the young but were usually well tolerated. This study suggests that injection sclerotherapy is useful in the treatment of bleeding oesophageal varices in the elderly and suggests recommendations for improved survival.
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Isoprenaline produced dose-dependent reductions of responses of the isolated uterus of the rat produced by an EC(80) of acetylcholine. Propranolol acted as a competitive antagonist to isoprenaline. Labetolol also reduced the acetylcholine-induced contractions but was much less potent than isoprenaline. The greatest reduction was smaller than that produced by isoprenaline. Propranolol antagonized the lower doses of labetolol. It is suggested that labetolol possesses partial agonist activity at the beta-adrenoceptors of the rat isolated uterus.