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Biomedical subjects

A Mackie

Publications and source records attributed to A Mackie.

At least 19 recordsLinked to original sources

Heel bone densitometry: device specific thresholds for the assessment of osteoporosis.

A diagnosis of osteoporosis is facilitated by bone mineral density (BMD) measurement of the lumbar spine and hip using dual energy X-ray absorptiometry (DXA), interpreted in accordance with criteria published by the World Health Organization (WHO). The use of peripheral DXA is growing in primary care and guidance on its use has recently been published by the National Osteoporosis Society (NOS), recommending a triage approach using thresholds specific to each type of peripheral device. However, no data currently exist for the Norland Apollo heel densitometer (Cooper Surgical, Trumbull, USA). 215 women between 50 years and 75 years of age (mean age 64.6 years) referred for hip and spine BMD measurements also had a heel BMD measurement. Device specific upper and lower thresholds were calculated for the Norland Apollo heel densitometer to give a 90% sensitivity and 90% specificity for osteoporosis at the hip or spine. Patients with a heel T-score of above -1.2 are very likely to have normal bone density on axial densitometry, whilst patients with heel T-score of below -2.2 are very likely to have osteoporosis at the hip or spine. Patients whose measurements lie between the thresholds should be referred for axial DXA.

Absorptiometry, Photon↗

Breast milk activity during early lactation following maternal 99Tcm macroaggregated albumin lung perfusion scan.

A breast feeding infant may receive a radiation dose from ingestion of breast milk following the administration of a radiopharmaceutical to the mother. The Administration of Radioactive Substances Advisory Committee recommendation to interrupt breast feeding may not necessarily apply in the period of early lactation when colostrum is being produced. Following a lung scan using 99Tcm macroaggregated albumin (MAA) on a patient approximately 15 h post partum, radioactivity within breast milk was measured. Milk was expressed approximately every 4 h during the day and samples were counted. The sample radioactivity concentration peaked at 15 h and decayed monoexponentially (half clearance time was approximately 4.8 h). The estimated effective dose to the infant from ingestion alone, had breast feeding not been interrupted, was approximately 0.02 mSv. These data suggest that interruption to breast feeding may not be necessary following administration of up to the diagnostic reference level of 99Tcm MAA during early lactation.

Adult↗

Eye-drop DNA can induce IgA in the tears and bile of chickens.

DNA vaccines protect chickens against lethal virus infections but whether they induce local antibody which is associated with preventing viral entry, is unknown. We were able to show how avian DNA vaccines can induce local IgA. 65 microg plasmid DNA encoding the reporter protein beta-galactosidase induced antigen-specific IgA in the tears of 6/10 birds, IgA in the bile of 4/10 birds and IgG in the serum of 2/10 birds. Giving the DNA by the intramuscular route, as is more usual, induced lacrimal IgA in 2/8 birds, biliary IgA in no birds and serum IgG in 4/8 birds. Eye-drop DNA therefore favoured local IgA whereas intramuscular DNA favoured serum IgG. Further to this preliminary work eye-drop DNA should be improved by adjuvants and cytokines as a way of inducing protective IgA at the mucosal surfaces of the alimentary and respiratory tracts.

Animals↗

Non-operative treatment of multidirectional shoulder instability.

At an average follow-up of 3.7 years we assessed the results of non-operative treatment of 84 symptomatic shoulders in 59 patients with a diagnosis of multidirectional shoulder instability. Sixty-two shoulders had received no previous surgical treatment (group A) while 22 had failed to respond to surgical treatment before the rehabilitation programme (group B). Subjectively 11 of the non-operated shoulders (group A) were cured and 27 improved, 23 of the shoulders remained the same and one was worse at follow-up. According to the age and gender adjusted Constant score, 38 of the non-operated shoulders had either no disability or only mild disability, nine had moderate disability, while the remaining 15 had severe or total disability. These figures were far worse in group B. In group A only four shoulders required operation, while in group B seven required operation following rehabilitation. Patients who had had previous shoulder surgery, those with a work related injury and those with psychological problems were less likely to benefit from the rehabilitation programme.

Adolescent↗

Fluorescence recovery after photobleaching reveals that LPS rapidly transfers from CD14 to hsp70 and hsp90 on the cell membrane.

Although CD14 has been implicated in the immune recognition of bacterial lipopolysaccharide (LPS) from Gram-negative bacteria and also peptidoglycan (PGN) and lipoteichoic acid (LTA) from the outer cell wall of Gram-positive bacteria, accumulating evidence has suggested the possible existence of other functional receptor(s). In this study, we have used fluorescence recovery after photobleaching (FRAP) in order to get the first dynamic picture of the innate recognition of bacteria. We have found that the diffusion coefficient of CD14 remains unaffected after LPS ligation and that the diffusion coefficients of FITC-LPS and FITC-LTA bound to cells differ from that of CD14. Furthermore, FITC-LPS/LTA rapidly become immobile when bound to cells, suggesting that FITC-LPS/LTA must briefly associate with CD14 in the initial attachment process and rapidly move on to an immobile receptor or to a complex of receptors. Further FRAP experiments revealed that heat shock protein 70 (hsp70) and hsp90 are immobile in cell membranes, and antibodies against them were found to block the transfer of LPS to the immobile receptor and to inhibit interleukin 6 production upon LPS stimulation. These experiments indicated that LPS transfers from CD14 to hsp70 and hsp90, which may be part of an LPS/LTA multimeric receptor complex. Thus, hsps are implicated as mediators of the innate activation by bacteria.

Animals↗

Evaluation of a panel of human monoclonal antibodies to D and exploration of the synergistic effects of blending IgG1 and IgG3 antibodies on their in vitro biologic function.

BACKGROUND: The D immunoprophylaxis program has successfully reduced the incidence of Rh hemolytic disease of the newborn (HDN), but it has also reduced the availability of plasma-derived polyclonal anti-D, which constitutes the current therapeutic product. Human monoclonal anti-D from hybridoma cell lines may be an acceptable alternative, and clinical efficacy of each anti-D is being evaluated in several centers. STUDY DESIGN AND METHODS: This study represents the largest assessment (outside of the International Workshops) of human D monoclonal antibodies for potential therapeutic use. The in vitro biologic activity and immunologic and serologic reactivity of a coded panel of 20 D antibodies (THERAD) was investigated. The bioassays used were lymphocyte (K-cell) antibody-dependent cell-mediated cytotoxicity (ADCC), monocyte ADCC, and monocyte chemiluminescence, which together reflect the processes involved in antibody-coated red cell destruction in vivo. From this panel, six antibodies (THERADs 14, 19, 22, 23, 27, and 28, comprising 3 IgG1 and 3 IgG3 D monoclonal antibodies) were further selected to investigate the effects of blending in the three bioassays. RESULTS: Several THERAD blends displayed greater activity than their component parts, in the range of 6 to 124 percent. There was no evidence to suggest functional blocking effects with this restricted panel of antibodies. CONCLUSION: The THERAD blends containing both IgG1 and IgG3 anti-D appeared to be the most functionally active, as did blends containing antibodies to two distinct D epitopes. This in vitro evidence has important implications for the future formulation of an effective monoclonal preparation for the prevention of Rh HDN.

Antibodies, Anti-Idiotypic↗

Lipid dynamics in the plasma membrane of fresh and cryopreserved human spermatozoa.

Preserving the integrity of the plasma membrane of spermatozoa is crucial for retention of their fertilizing capacity, especially after stressful procedures such as freezing and storage. In this investigation we have measured lipid diffusion in different regions of the plasma membrane of fresh and cryopreserved human spermatozoa using a sensitive, high resolution fluorescence photobleaching technique (FRAP) with 5-(N-octadecanyl)aminofluorescein as reporter probe. Results show that diffusion was significantly faster on the plasma membrane overlying the acrosome and decreased progressively in the postacrosome, midpiece and principal piece. The midpiece plasma contains a higher proportion of immobile lipids than other regions. In cryopreserved spermatozoa, lipid diffusion in the plasma membrane was significantly reduced on the acrosome, postacrosome and midpiece relative to fresh spermatozoa. Diffusion, however, could be restored to normal levels by washing spermatozoa in a medium containing 0.4% polyvinylpyrrolidine but not in medium alone or in medium containing 0.4% albumin. These results suggest that (i) lipid dynamics in the plasma membrane of human spermatozoa varies significantly between surface regions; (ii) in-plane diffusion is adversely affected by cryopreservation; and (iii) washing frozen spermatozoa in 0.4% polyvinylpyrrolidine restores membrane lipid fluidity to normal levels. The latter finding has important implications for improving the fertility of human spermatozoa following cryopreservation.

Adult↗

A 'one-stop' vascular clinic: initial experience of an out-patient immediate-access radioisotope limb blood flow service.

The availability of an 'immediate-access' nuclear medicine service has facilitated the introduction of a 'one-stop' vascular clinic, enabling radioisotope limb blood flow and Doppler ankle:brachial index tests to be performed within 2 h of each other for new patient referrals. The test results are available to assist clinical management decisions during the same clinical session. A patient satisfaction survey was undertaken in 71 patients to assess their perspective of this service provision. Fifty-one (72%) patients returned the questionnaire. All respondents preferred to have attended the 'one-stop' clinic to having to return for investigations on a separate occasion. The patient satisfaction survey has identified patient perceived advantages of improved diagnostic efficiency, reduced number of visits, reduced patient worry and the minimization of patient travel costs. During the study period, 83% of allocated gamma-camera imaging slots were utilized, demonstrating that immediate-access nuclear medicine service provision linked to specific clinics can be a practicable solution to reducing waiting times for investigative tests. This is believed to be the first reported immediate-access nuclear medicine service, as opposed to the emergency investigations normally offered to clinically urgent requests.

Ambulatory Care Facilities↗

Changes in esophageal function after vertical banded gastroplasty as demonstrated by esophageal scintigraphy.

BACKGROUND: The effects of surgery for morbid obesity on the function of the upper gastrointestinal (GI) tract are of interest to bariatric surgeons. This study was undertaken to determine any changes in esophageal function, following vertical banded gastroplasty (VBG) in morbidly obese patients, as detected by esophageal scintigraphy. METHODS: Ten consecutive morbidly obese patients (six female and four male) underwent preoperative esophageal scintigraphy and upper GI endoscopy. These investigations were repeated 12 months after VBG to coincide with expected appreciable weight reduction. The results were tabulated together with body mass indices, crude weights and percentage excess weight lost. RESULTS: Before VBG one patient gave a history of mild heartburn, one had mild dyspepsia and the remaining eight patients had no GI symptoms. No patient had a hiatus hernia or endoscopic evidence of reflux esophagitis. Preoperatively all patients had abnormal scintiscans. The abnormalities were esophageal retention (all) and intraesophageal reflux (five out of 10 patients). Gastroesophageal reflux was not identified in any patient. Postoperatively scintiscans were normal or improved in six out of 10 patients and unchanged in four out of 10 patients. In three patients the scans were normal and three showed overall improvement in esophageal function, although in one of these latter patients gastroesophageal reflux was observed. CONCLUSIONS: In this series of morbidly obese patients, esophageal function as assessed by scintigraphy was abnormal. Following VBG it improved in six out of 10 patients and was unchanged in four out of 10. However, in one patient, who had shown an overall improvement in esophageal function, gastroesophageal reflux was demonstrated when it had not been seen preoperatively. This was asymptomatic. Thus, adverse changes in esophageal function after VBG were uncommon.

Adolescent↗

Ramp test objects for slice sensitivity profile measurement in spiral CT.

Spiral CT is increasingly becoming a routine imaging technique in the UK. The ability to scan whole organs within a single breath-hold often demands that the scan pitch (ratio of the patient translation distance per tube rotation (d) to the collimated slice thickness) be increased within technically acceptable limits. It is known that the full width at half maximum height (FWHM) of the slice sensitivity profile (SSP), degrades with increasing scan pitch and also varies with interpolation algorithm. Published literature frequently reports values for FWHM of the SSP for spiral acquisitions which have been measured with a ramp test tool. However, it has previously been shown that a ramp is inappropriate for SSP measurements in spiral CT. This is because of the physical basis of the premise for this measurement and the large artefacts generated by the application of the interpolation algorithm to the ramp spiral projection data. We present experimental evidence confirming the unsuitability of the ramp test tool in spiral CT. A cyclical variation (d/2) of the data is demonstrated; the magnitude of the measured SSP being dependent upon scan pitch and the interpolation algorithm used, as well as on the longitudinal position of the reconstruction plane.

Humans↗

Programmable dynamic line phantom control: an initial assessment of quantitative potential as a gamma camera test tool.

The dynamic line phantom (DLP) produces various test patterns for the qualitative assessment of gamma camera performance, by stepper motor control of the translatory movement of a radioactive rigid line source. The addition of a V24 serial interface port has allowed external control via an RS-232 connection to a personal computer. Programmability has enabled the DLP to be used as a quantitative test tool. One such program produces a variable contrast 'hot' and 'cold' bar pattern. The addition of a Quick Basic computer program modifies the line source movement to compensate for variation in line source activity. This maintains a test pattern with fixed, absolute contrast levels, giving the potential for the measurement of variations in long-term imaging performance. A modulation transfer function (MTF) pattern has been designed which encompasses a sinusoidally varying intensifying function with a changing spatial frequency component. Repeated measurements on two gamma cameras demonstrated poor reproducibility (CV of up to 50% dependent upon spatial frequency) and significant differences between the MTF obtained from line spread function measurements (percentage deviation of up to 23%, dependent upon spatial frequency). Neither test pattern has been adopted for routine quantitative assessment of gamma camera imaging characteristics. The reproducibility of results is poor (dominated by counting statistic limitations), making the techniques insensitive to small changes in camera performance.

Gamma Cameras↗

Does the Hawksley random zero sphygmomanometer underestimate blood pressure, and by how much?

The study objective was to compare blood pressure (BP) measurement by the Hawksley random-zero sphygmomanometer and the standard mercury sphygmomanometer. Comparison of simultaneous 'blind' BP measurements were made using the Hawksley random-zero sphygmomanometer and the standard mercury sphygmomanometer linked by a Y-connector to a single cuff, in the general practice and office environments. Sixty five healthy volunteers and general practice patients, aged between 20 and 50 years (SBP range 82-184 mm Hg, DBP range 38-112 mm Hg), were studied. Each had three blood pressure measurements taken. Mean BPs recorded by the Hawksley random-zero sphygmomanometer were lower than those recorded by the standard mercury sphygmomanometer. The Hawksley random-zero sphygmomanometer underestimated SBP by 1.3 mm Hg (95% CI 0.9-1.8 mm Hg) and DBP by 1.7 mm Hg (95% CI 1.1-2.3 mm Hg). These differences between instruments were independent of BP level both for systolic and diastolic measurements. An overview including this study and six other published reports describing nine studies examining the performance of the Hawksley random-zero sphygmomanometer suggested a similar degree of underestimation for SBP (mean difference 1.35 mm Hg, 95% CI 1.24-1.46 mm Hg). Underestimation of DBP appeared greater (mean difference 2.54 mm Hg, 95% CI 2.43-2.65 mm Hg) but was reduced when two outlying studies were removed from analysis (mean 1.97, 95% CI 1.85-2.09 mm Hg). We conclude that the Hawksley random-zero sphygmomanometer underestimates systolic and diastolic pressure, when compared with the standard mercury sphygmomanometer. However, the degree of underestimation is small and appears consistent across a wide range of blood pressure levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Airborne radioactive contamination following aerosol ventilation studies.

Lung aerosol ventilation studies may be accompanied by airborne contamination, with subsequent surface contamination. Airborne contamination has been measured prior to, during and following 59 consecutive 99Tcm-diethylenetriamine pentaacetate (DTPA) aerosol studies using a personal air sampler. Airborne contamination ranging between 0 and 20 330 kBq m-3 has been measured. Airborne contamination increases with degree of patient breathing difficulty. The effective dose equivalent (EDE) to staff from ingested activity has been calculated to be 0.3 microSv per study. This figure is supported by data from gamma camera images of a contaminated staff member. However, surface contamination measurements reveal that 60% of studies exceed maximum permissible contamination limits for the hands; 16% of studies exceed limits for controlled area surfaces. The EDE from ingestion is low, but protective clothing is essential to prevent body and clothing contamination. Ingested activity and surface contamination results from this study have been compared with results from a Technegas study.

Aerosols↗

Lipoprotein(a) in type 1 diabetic patients with renal disease.

Lp(a) was measured in 64 normoalbuminuric, 52 microalbuminuric, and 37 proteinuric Type 1 diabetic patients and 54 healthy subjects. Microalbuminuric and proteinuric Type 1 diabetic patients had higher median Lp(a) values (133 (16-1932) and 169 (17-1149) mg l-1) than patients with normal AER (73 (15-1078) mg l-1; p = 0.048 and p = 0.027). Lp(a) in healthy subjects (110 (15-1630)mg l-1) did not differ from the diabetic subgroups. The frequency of Lp(a) values in the upper quarter of the normal distribution was similar in the diabetic groups and did not differ between diabetic and control subjects. The cumulative distribution of Lp(a) was similar in all groups. Lp(a) concentrations were not related to AER, age, gender, duration of diabetes, body mass index, glycaemic control, serum creatinine, free insulin or systolic blood pressure. Cholesterol, LDL-cholesterol, triglycerides, and apo B were higher in microalbuminuric and proteinuric than in normoalbuminuric Type 1 diabetic patients. Lp(a) was independently related to diastolic blood pressure, fibrinogen, and macroangiopathy. In conclusion, median Lp(a) concentrations tend to be higher in Type 1 diabetic patients with early and established renal disease, although the differences are small and the overlap between groups large. Lp(a) is related to diastolic blood pressure and fibrinogen, and this association of powerful risk factors suggests that Lp(a) may play a role in the pathogenesis of cardiovascular disease in Type 1 diabetic patients with proteinuria. Whether Lp(a) is an independent determinant of increased cardiovascular risk in these patients needs to be elucidated by prospective studies.

Adult↗

Beta-adrenoceptor subtypes mediating the airways response to BRL 35135 in man.

1 The purpose of the study was to assess the bronchorelaxant effects of the beta3-adrenoceptor agonist BRL 35135 in normal human airways. 2 Eight healthy male subjects were studied, having previously demonstrated airways responsiveness to inhaled salbutamol 200 microg, with a group mean (+/- s.e. mean) fall in airways resistance (Raw), from baseline, of 37 +/- 5%. 3 Subjects attended the laboratory on 3 separate days, having fasted and taken placebo (PL) or nadolol 20 mg (N20), 2 h previously. 4 After 30 min rest, baseline measurements of Raw, serum potassium, glucose and free fatty acid were performed before subjects were given single oral doses of BRL 35135 8 mg (BRL) or placebo BRL. Measurements were repeated 60 min after the BRL or placebo BRL were given. 5 There was a significant (P < 0.05) fall in Raw (% change from baseline, as means and 95% CI) with PL/BRL: -32(-18, -46), compared with either PL/PL: -8(5, -21), or N20/BRL: -11(2, -24). There was no significant difference between PL/PL and N20/BRL. 6 A similar pattern to Raw was observed for both of the beta2-mediated metabolic responses which were also antagonised by nadolol. For the potassium response (mmol l(-1)), there was a significant (P < 0.05) difference between PL/BRL: -0.50(-0.31, -0.69), in comparison with either PL/PL: 0.08(-0.11, 0.27) or N20/BRL: 0.09(-0.10, 0.28), but values for PL/PL and N20/BRL were not significantly different. In contrast, with the free fatty acid response (nmol 1(-1)), the increase seen with N20/BRL: 85(1.0, 171.0) was significantly (P < 0.05) different from PL/PL: 3.7(-82.3, 89.8), but was not different from PL/BRL: 132.5(46.5, 218.5). 7 In conclusion, BRL 35135 produced airways, potassium and glucose responses which were antagonised by nadolol, whereas the lipolysis response was not. This suggests that there are not functional beta3-adrenoceptors in human airways.

Adrenergic alpha-Agonists↗

Synthesis of digoxigenin-labeled cRNA probes for nonisotopic in situ hybridization using reverse transcription polymerase chain reaction.

Nonisotopic methods of mRNA in situ hybridization have distinct advantages over isotopic techniques. Nonisotopically labeled probes are stable and nontoxic, have short detection times, demonstrate excellent spatial resolution of their signals and have sensitivities comparable to radiolabeled probes. We developed a simple method of generating nonisotopically labeled cRNA probes which is based on the reverse transcription polymerase chain reaction (RT-PCR) and used it to synthesize a panel of probes for various murine extracellular matrix genes. Engelbreth-Holm-Swarm (EHS) tumor RNA was reverse transcribed and PCR was used to amplify defined regions of multiple extracellular matrix protein genes from the resulting first strand cDNAs. Bacteriophage promoters which had been incorporated into the PCR products were then used to generate digoxigenin-conjugated antisense and sense cRNAs. The antisense probes were employed to detect the specific extracellular matrix protein mRNAs in the EHS tumor by in situ hybridization. This technique provides a rapid and efficient alternative to conventional transcription systems which use plasmid vectors for the synthesis of digoxigenin-labeled cRNA probes.

Animals↗