Accident and emergency medicine or emergency medicine.
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Accidents↗
Biomedical subjects
H Simpson
Publications and source records attributed to H Simpson.
Clinical experience in identical twins discordant for adult-onset growth hormone deficiency.
The syndrome of adult-onset growth hormone (GH) deficiency is well established. However uncertainties exist regarding monitoring of the therapeutic response. Currently the Growth Hormone Research Society consensus statement recommends monitoring GH replacement by taking a history, with attention to questions relating to quality of life, physical examination, body composition (by a suitable method) and measurement of insulin-like growth factor (IGF)-I. With the advent of commercially available assays for IGF binding protein (IGFBP)-3 and acid-labile subunit (ALS) it was hoped that it might prove possible to develop a more sensitive protocol for monitoring GH replacement therapy. We are in the unique position of having three patients with GH deficiency who are one of a pair of monozygotic twins, in which the second twin is healthy. We studied the effect of recombinant GH (rhGH) therapy (0.0375 U/kg) in the GH-deficient twin, and compared pre- and post-rhGH variables with similar observations in the healthy twin. Body composition, IGF-I, IGFBP-3 and ALS levels were measured before and after 3 months of rhGH therapy. Body composition changed as expected most impressively in twin 1; twins 1 and 2 had low IGF-I, IGFBP-3 and ALS prior to treatment with GH, but normal concentrations that were similar to those of their healthy twin were attained after 3 months of GH treatment. Twin 3 had normal IGF-I, IGFBP-3 and ALS concentrations before GH treatment, which were similar to those of her twin. Interestingly she also had a high fasting insulin level. After GH replacement these concentrations increased but remained within the normal range, similar to those of her healthy twin. Insulin and GH have both been shown to stimulate hepatic production of IGF-I and these results suggest that insulin may also be involved in the regulation of IGFBP-3 and ALS in vivo. Insulin has already been implicated in the regulation of IGFBP-3 and ALS in vitro and there is some evidence to suggest that this is also the case in vivo. We conclude that clinical state, body composition and IGF-I assessed together remain the best methods of monitoring GH replacement therapy and that measurements of IGFBP-3 and ALS do not confer any advantage over IGF-I.
Adult↗
Mobile retinal screening in Britain.
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Diabetic Retinopathy↗
High throughput liquid chromatography/mass spectrometry bioanalysis using 96-well disk solid phase extraction plate for the sample preparation.
The 96 well solid phase extraction (SPE) operated by robot in the LC/MS/MS bioanalysis offered rapid sample preparation for drugs and metabolites in biological matrices, based on simultaneous extraction of 96 samples. The use of a disk as sorbent in the 96 well plate further improved the performance of SPE and allowed for small elution volumes, making it possible to 'dilute and shoot" after SPE elution. In this study, a 96 well plate (Empore) was developed, characterized and optimized for several pharmaceutical compounds. In addition, a robot (MultiProbe) was modified to automate the 96 well plate operation. Examples were given to illustrate the major differences of using 96 well disk plate SPE in the method development as compared to the traditional SPE. This technology has been successfully used to support many clinical studies. Typically, a batch of 96 samples were prepared in 1-1.5 hours unattended (except for the replacement of a collection plate). Considerable savings in disposable supplies were also noted.
Anti-Asthmatic Agents↗
Recurrent cough: natural history and significance in infancy and early childhood.
We investigated the outcome for a sample of children in whom recurrent cough was reported in the preschool years to determine 1) whether they shared the characteristics attributed to cough variant asthma, and 2) the proportion who developed classical wheezy asthma at follow-up during the early school years. A cohort of children identified as having recurrent cough in the preschool period was reassessed during the early school years. Previously identified asymptomatic preschool children who remained symptom-free provided a comparison group with respect to current respiratory symptoms, lung function, bronchial reactivity to inhaled methacholine, atopic status, peak flow variability, and recorded night cough. The response rate was modest, with 41% attending the follow-up study; information on current symptoms was available from a further 16%. Ascertainment of current symptoms showed that 70 of 125 (56.0% [95% CI 47.3-64.5%]) were symptom-free at follow-up, 46 (36.8% [28.7-45.5%]) continued to have recurrent cough in the absence of colds, and 9 (7.2% [3.6-12.8%]) reported recent attacks of wheeze. When comparing the 46 children whose recurrent cough persisted from the preschool period through to follow-up with subjects from the asymptomatic comparison group, the former had significantly more night cough (50.0% vs. 16.8%; P< 0.01), were more likely to be treated (10.9% vs. 1.7%; P=0.01), or were diagnosed (26.1% vs. 5.7%; P < 0.001) as asthmatic. They also showed greater bronchial reactivity than their asymptomatic counterparts (1.23 mg/ml vs. 3.35 mg/ml; P=0.002). Atopic status and other indices of lung function were similar between groups. We conclude that there are a group of children with long-term recurrent cough who display features consistent with a diagnosis of cough variant asthma, but at 2-4 years of follow-up, few progress to develop asthma characterized by wheeze.
Asthma↗
Lung abscess: an unusual presentation of congenital tracheoesophageal fistula without atresia.
Tracheoesophageal fistula (TEF) without atresia is rare and usually presents with symptoms from birth. In this report, a 9-year-old boy presented with productive cough of 4 month's duration and was shown to have a right lung abscess seen on chest radiograph. His parents denied earlier respiratory symptoms or illnesses. Rigid bronchoscopy showed a fistulous opening of about 1 mm in diameter in the posterior wall of the trachea about 16 cm from the upper incisor teeth. Cannulation with a ureteral catheter demonstrated that the fistulous opening communicated with the esophageal lumen. The tracheoesophageal fistula was 1 cm long and was divided through a right supraclavicular incision. The postoperative period was uneventful, and the patient was discharged on the third postoperative day. This case demonstrated that TEF should be considered in any patient presenting with chronic respiratory problems even after a prolonged symptom-free period.
Bronchoscopy↗
Temporal variation of applied inter fragmentary displacement at a bone fracture in harmony with maturation of the fracture callus.
The amplitude of inter fragmentary displacement in long bone fractures greatly influences the pattern and speed of healing. Unfortunately, the amplitude of natural cyclical displacement arising from patient activity is random because of the inherent flexibility of fixation devices under natural loading. Although fixators may be designed to control the amplitude of this displacement, the amplitudes most beneficial to healing have not been determined. Furthermore, the appropriate amplitude must vary during healing as the reparative tissue (callus) progresses histologically and stiffens during maturation. In this study on an experimental fracture, the amplitude of applied cyclical displacement is varied during healing to correspond with the inverse of the callus stiffness versus time curve. In vivo mechanical stiffness tests on the callus indicate that the end point of the fixation period is achieved more rapidly than with a constant level of applied displacement.
Animals↗
The morphological basis of increased stiffness of rabbit tibialis anterior muscles during surgical limb-lengthening.
When the tibialis anterior muscle of the rabbit is progressively stretched during surgical limb distraction, the muscle fibres lengthen by addition of new serial sarcomeres, provided that stretch is carried out at an appropriate rate. However, in spite of the apparent adaptation to the new functional length, range of joint movement is greatly decreased. In this study we have first, made measurements of the passive tension developed by distracted muscles over the range of joint movement and secondly made quantitative measurements of endomysial and perimysial connective tissue content. It was found that at all ankle joint angles greater than 90 degrees, the passive tension developed by the distracted muscles was greater than both contralateral and sham-operated controls. Image analysis showed that the ratio of collagen to contractile material was increased in distracted muscles compared with muscles from sham-operated controls, due to increased deposition of collagen type III. Scanning electron microscopy showed the presence of a dense perimysial weave surrounding the distracted muscle fibres. These quantitative and qualitative changes in the connective tissue component could account for the increased stiffness demonstrated by the physiological measurements. It would seem that in distracted muscle the connective tissue element adapts less readily than the contractile component, with prolonged stretch leading to damage to the perimysial and endomysial network, with subsequent fibrosis and loss of muscle compliance. Such changes could help explain the loss of range of movement noted in the distracted limbs of patients undergoing surgical limb-lengthening and in other conditions that result in muscle contractures.
Adaptation, Physiological↗
Prospective evaluation of criteria for microbiological diagnosis of prosthetic-joint infection at revision arthroplasty. The OSIRIS Collaborative Study Group.
A prospective study was performed to establish criteria for the microbiological diagnosis of prosthetic joint infection at elective revision arthroplasty. Patients were treated in a multidisciplinary unit dedicated to the management and study of musculoskeletal infection. Standard multiple samples of periprosthetic tissue were obtained at surgery, Gram stained, and cultured by direct and enrichment methods. With reference to histology as the criterion standard, sensitivities, specificities, and likelihood ratios (LRs) were calculated by using different cutoffs for the diagnosis of infection. We performed revisions on 334 patients over a 17-month period, of whom 297 were evaluable. The remaining 37 were excluded because histology results were unavailable or could not be interpreted due to underlying inflammatory joint disease. There were 41 infections, with only 65% of all samples sent from infected patients being culture positive, suggesting low numbers of bacteria in the samples taken. The isolation of an indistinguishable microorganism from three or more independent specimens was highly predictive of infection (sensitivity, 65%; specificity, 99.6%; LR, 168.6), while Gram staining was less useful (sensitivity, 12%; specificity, 98%; LR, 10). A simple mathematical model was developed to predict the performance of the diagnostic test. We recommend that five or six specimens be sent, that the cutoff for a definite diagnosis of infection be three or more operative specimens that yield an indistinguishable organism, and that because of its low level of sensitivity, Gram staining should be abandoned as a diagnostic tool at elective revision arthroplasty.
Arthroplasty, Replacement, Hip↗
Images in medicine. Retroperitoneal haematoma.
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Aged↗
Expression of BMP-4 mRNA during distraction osteogenesis in rabbits.
We characterized the presence and localization of bone morphogenetic protein 4 (BMP-4) mRNA in the regenerating tissues produced by distraction osteogenesis following tibial osteotomy in the rabbit. The findings are consistent with previous reports on the localization of BMP-4 mRNA expression during fracture repair. The BMP-4 gene is expressed by less differentiated osteoprogenitor cells (fibroblastic mesenchymal cells and preosteoblasts), and not by fully differentiated osteoblasts. BMP-4 gene expression is localized in callus-forming tissue (muscle, periosteum) during callus formation. Our observations suggest that the BMP-4 gene product is one of the local contributing factors in regulating bone and cartilage formation in distraction osteogenesis.
Animals↗
Putting evidence into practice.
A training module is described in which experienced health care managers from developing countries explore the challenges to be faced when attempting to use the results of systematic reviews of scientific studies on health care interventions in policy and practice.
Decision Making↗
Influence of apo E phenotype on postprandial triglyceride and glucose responses in subjects with and without coronary heart disease.
Apolipoprotein E phenotypes and fasting lipid and other biochemical parameters were determined in 51 patients with recently diagnosed coronary heart disease (CHD) and 164 control subjects. The age of the participants was 62.5 +/- 6.6 (S.D.) and 63% were male. Forty-eight CHD cases and 51 control subjects were also studied for 8 h after a fat-rich meal. Apo E phenotypes did not differ significantly between CHD cases and control subjects although there was a tendency for under-representation of E2/E3 in the cases (6% versus 16%). Fifteen CHD cases and 37 (of 164) control subjects had at least one epsilon 4 allele. Fasting plasma triglyceride concentrations were not different between CHD cases and controls but were significantly elevated in subjects with an epsilon 4 allele. CHD cases did, however, have a significantly elevated fasting insulin compared with controls. Postprandial triglyceride responses were not different between CHD cases and controls. However, postprandial triglyceride responses were elevated in subjects (CHD cases and controls) who had an epsilon 4 allele. In multivariate analysis, both epsilon 4 allele status and body mass index (BMI) were significant determinants of postprandial triglyceride responses. Postprandial glucose responses were also elevated in subjects with an epsilon 4 allele. When comparison of CHD cases and controls was restricted to those without an epsilon 4 allele, CHD cases showed a borderline significant (P = 0.05) difference in time course from controls, with a slower decline in plasma triglyceride from the peak response. Fasting and postprandial triglyceride and postprandial glucose responses are strongly dependent on the presence of an epsilon 4 allele. The elevation in postprandial triglyceride responses associated with an epsilon 4 allele can obscure differences associated with the presence of CHD and suggests that although elevated postprandial triglyceride response may be a risk factor for CHD, it is not the major reason for the association between the possession of an epsilon 4 allele and coronary disease.
Aged↗
Relation between saliva flow and flavor release from chewing gum.
The objective of this study was to investigate whether or not parotid saliva flow is a significant determinant of flavor release from chewing gum. Cherry-flavored gum with 3 concentrations of citric acid (0.5, 1, and 2%) acting as a sialagogue was evaluated for sweetness and cherry flavor in duplicate by 13 subjects, using a computerized system for simultaneous time-intensity (TI) measurements and unilateral collection of parotid saliva. With increased acidity in the gum, maximum intensity of, and area under, the cherry flavor curve increased (p < 0.001), whereas total duration of sweetness decreased (p < 0.05). Large interindividual differences were found for parotid saliva flow in response to chewing gum. Mean unilateral parotid saliva flows in response to stimulation with water and gum with 0.5, 1, and 2% citric acid were 0.07, 0.30, 0.36, and 0.44 g/min, respectively. There was a significant positive correlation between saliva flow and time to reach maximum intensity of sweetness (p < 0.05) and of cherry flavor (p < 0.01), with "high-flow" subjects taking longer to reach maximum intensity than "low-flow" subjects for both attributes. We conclude that parotid saliva flow may affect the rate of flavor release, but not how much nor for how long flavor is released.
Adult↗
The terminal oxidase in the marine bacterium Pseudomonas nautica 617.
The molecular properties of a novel membrane quinol oxidase from the marine bacterium Pseudomonas nautica 617 are presented. The protein contains 2b hemes/mole which may be distinguished by EPR spectroscopy but not by optical spectroscopy and electrochemistry. Respiration, though being cyanide insensitive, is not inhibited by carbon monoxide and oxygen reduction is carried out only half-way with production of hydrogen peroxide. The terminal oxidase represents, therefore, a unique example in the large family of terminal oxidases known up to date.
Hydrogen Peroxide↗
Changes in muscle fibre type, muscle mass and IGF-I gene expression in rabbit skeletal muscle subjected to stretch.
The relationship between IGF-1 and changes in muscle fibre phenotype in response to 6 d of stretch or disuse of the lower limb muscles of the rabbit was studied by combining in situ hybridisation and immunohistochemistry procedures. Passive stretch by plaster cast immobilisation of the muscle in its lengthened position not only induced an increase in IGF-I mRNA expression within the individual muscle fibres but also an increase in the percentage of fibres expressing neonatal and slow myosin. This change in phenotype was also found to be accompanied by a rapid and marked increase of muscle mass, total RNA content as well as IGF-I gene expression. In contrast, IGF-I appears not to be involved in muscle atrophy induced by immobilisation in the shortened position and the inactivity which results from this procedure. The level of increase in expression of IGF-I mRNA varied from fibre to fibre. By using adjacent serial sections, the fibres which expressed IGF-I mRNA at the highest levels were identified as expressing neonatal and the slow type 1 myosin. These data suggest that the expression of IGF-I within individual muscle fibres is correlated not only with hypertrophy but also with the muscle phenotypic adaptation that results from stretch and overload.
Adaptation, Physiological↗
Risk factors for coronary heart disease in a population with a high prevalence of obesity and diabetes: a case-control study of the Polynesian population of Western Samoa.
OBJECTIVE: To evaluate anthropometric, haemodynamic and biochemical risk markers for coronary heart disease (CHD) in the Polynesian population of Western Samoa in a case-control study of 43 cases of CHD compared with 90 age- (mean 53 years) and sex-matched controls. METHODS: Cases were identified on the basis of a 12-lead electrocardiogram and clinical history. RESULTS: More than 60% of the participants had a body mass index > or =30 kg/m2 and nearly 80% had central obesity. Both diabetes mellitus (17%) and impaired glucose tolerance (9%) were also common in this population. Nineteen per cent of the population were hypertensive and both antihypertensive therapy (21 versus 1%, P<0.001, risk 23.6) and hypertension (35 versus 11%, P<0.01, risk 4.3) were significantly more common among cases than they were among controls. In addition, the plasma high-density lipoprotein cholesterol level was lower (1.00+/-0.09 versus 1.24+/-0.05 mmol/l, P<0.05) and the plasma urate level was higher (0.42+/-0.02 versus 0.37+/-0.01 mmol/l, P<0.05) in the female cases than they were in their respective controls. Low-density lipoprotein (LDL) particle sizing did not reveal an excess of small LDL particles to be a feature of CHD cases, but more than 70% both of cases and of controls had multiple LDL species. The response of the triglyceride level to a fat-rich meal was the same for CHD cases and controls. CONCLUSION: The population studied had a high prevalence of several risk factors for CHD, including obesity and non-insulin-dependent diabetes mellitus; however, the most prominent factor relating to CHD within the community was the presence of hypertension.
Adult↗
LDL particle size in subjects with previously unsuspected coronary heart disease: relationship with other cardiovascular risk markers.
Low density lipoprotein (LDL) particle diameters were determined by non-denaturing gradient gel electrophoresis in 53 subjects with previously unrecognised coronary heart disease (CHD) and 167 control subjects matched by age, sex and total plasma cholesterol. The mean diameter of the major LDL peak was found not to be significantly different between the two groups, but the CHD subjects were found to have a broader distribution of the predominant LDL species ((25.0 (24.7-25.3)nm versus 24.8 (24.7-24.9)nm)) (median (25-75%)), a greater proportion of larger particles (chi 2 = 19.8, P < 0.001) and to be more likely to have multiple numbers of LDL species than the control subjects (chi 2 = 22.7, P < 0.001). A negative correlation was found between the diameter of the predominant LDL species and fasting plasma triglyceride (r = -0.21, P = 0.0015), waist to hip ratio (WHR) (r = -0.15, P = 0.026) and body mass index (BMI) (r = -0.20, P = 0.002), and in a subgroup of subjects (n = 106), postprandial analysis revealed a negative correlation with the incremental postprandial response of plasma insulin (r = -0.19, P = 0.025). Male subjects had a significantly smaller diameter of the major LDL peak (24.8 +/- 0.0 nm) than female subjects (25.0 +/- 0.0 nm, P < 0.001). The present study failed to confirm an association between small LDL particles and the presence of coronary heart disease but did demonstrate more LDL heterogeneity in those with CHD. In addition, significant relationships were evident between the diameter of the major LDL peak and a number of other risk factors for coronary disease.
Anthropometry↗