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Biomedical subjects

A Burch

Publications and source records attributed to A Burch.

At least 19 recordsLinked to original sources
PubMed2005

Radiation doses received in the UK Breast Screening Programme in 2001 and 2002.

The mean glandular doses (MGD) to samples of women attending for mammographic screening are measured routinely at screening centres in the UK Breast Screening Programme (NHSBSP). This paper reviews a large representative sample of dose measurements collected during screening in the NHSBSP in 2001 and 2002 for 53 218 films, using 290 X-ray sets, for 16 505 women. The average MGD was 2.23 mGy per oblique film and 1.96 mGy per craniocaudal film; similar to those found previously in the NHSBSP for the years 1997 and 1998. Increasing use of sophisticated units with automatic beam quality selection has reduced the radiation dose received by large breasts, with only 2% of oblique mammograms having doses in excess of 5 mGy. The increasing use of large format film has also reduced the doses to this sub-group. However the total dose per woman has increased due to the introduction of two view screening at every visit. The MGD to the standard breast was found to vary from 0.76 mGy to 2.29 mGy, with 97% of units below the recommended upper limit of 2 mGy, illustrating the benefit of strict quality control. A reduction in dose of 3% was observed between the age bands 50-54 years and 60-64 years. This study has confirmed that the proposed national diagnostic reference level (NDRL) of 3.5 mGy for 55 mm thick breasts is an appropriate value to identify systems giving unusually high doses, with just 3.5% of systems exceeding this level. In most cases these higher doses were explained by the design of one particular make of X-ray set and its mode of operation. Average doses for oblique views of average sized breasts were fairly well correlated with the dose to the standard breast, and typically 42% higher. This highlights the need for a revised definition of the standard breast used in the UK to better reflect the exposure factors and doses received in clinical practice.

Age Factors↗
PubMed2000

Radiation doses received in the UK Breast Screening Programme in 1997 and 1998.

The mean glandular doses (MGDs) to samples of women attending for mammographic screening are measured routinely at screening centres in the UK Breast Screening Programme (NHSBSP). This paper reviews the data collected during screening in the NHSBSP in 1997 and 1998 for 23,752 films, using 171 X-ray sets, for 8745 women. Average MGD was 2.03 mGy per oblique film and 1.65 mGy per craniocaudal film, similar to the MGDs found previously in the NHSBSP for the years 1994 and 1995. MGD was found to increase with compressed breast thickness where the tube potential was selected manually, so that the average dose for 10 cm thick breasts was 2.7 times the average for all breasts. For large breasts (> 70 mm) the use of X-ray sets such as the IGE DMR, which automatically select the beam quality for each breast, resulted in lower doses compared with sets using manual tube potential selection. MGD to the standard breast was found to vary from 0.7 to 2.2 mGy and to be correlated with the average MGD per mediolateral oblique film for the women screened on that system (R = 0.79). No correlation between age and MGD was found within the invited age range of 50-64 years.

Age Factors↗
PubMed1999

The role of scaffolding proteins in the assembly of the small, single-stranded DNA virus phiX174.

An empty precursor particle called the procapsid is formed during assembly of the single-stranded DNA bacteriophage phiX174. Assembly of the phiX174 procapsid requires the presence of the two scaffolding proteins, D and B, which are structural components of the procapsid, but are not found in the mature virion. The X-ray crystallographic structure of a "closed" procapsid particle has been determined to 3.5 A resolution. This structure has an external scaffold made from 240 copies of protein D, 60 copies of the internally located B protein, and contains 60 copies of each of the viral structural proteins F and G, which comprise the shell and the 5-fold spikes, respectively. The F capsid protein has a similar conformation to that seen in the mature virion, and differs from the previously determined 25 A resolution electron microscopic reconstruction of the "open" procapsid, in which the F protein has a different conformation. The D scaffolding protein has a predominantly alpha-helical fold and displays remarkable conformational variability. We report here an improved and refined structure of the closed procapsid and describe in some detail the differences between the four independent D scaffolding proteins per icosahedral asymmetric unit, as well as their interaction with the F capsid protein. We re-analyze and correct the comparison of the closed procapsid with the previously determined cryo-electron microscopic image reconstruction of the open procapsid and discuss the major structural rearrangements that must occur during assembly. A model is proposed in which the D proteins direct the assembly process by sequential binding and conformational switching.

Amino Acid Sequence↗
PubMed1998

A pilot survey of radiation doses received in the United Kingdom Breast Screening Programme.

A survey of radiation dose and compressed breast thickness was conducted in samples of women undergoing mammography in the United Kingdom National Health Service breast screening programme. The aims were to determine the average value and distribution of dose and thickness, and to identify technical difficulties in carrying out such a survey. Values of breast thickness and mean glandular dose, calculated from exposure factors and measured X-ray beam parameters, were collected for 4633 women in 92 screening units in 1994 and 1995. The median (lower quartile, upper quartile) dose per film was 1.7 (1.2, 2.4) mGy for the mediolateral oblique view (mean thickness 57 mm) and 1.4 (1.1, 2.0) mGy for the craniocaudal view (mean thickness 52 mm). The median dose per woman was 1.8 (1.3, 2.5) mGy for a one-view examination and 3.3 (2.3, 4.6) mGy for a two-view examination. The dose per film showed an exponential relationship to breast thickness, but no relationship was found between median dose and median breast thickness in the different screening units, possibly because of errors in breast thickness measurement. The values of breast thickness and dose were generally consistent with those in other published surveys, allowing for differences in radiographic technique. No relationship between breast dose and standard optical density was demonstrated. Some recommendations for the conduct of future surveys of breast dose in the UK are proposed.

Breast↗
PubMed1998

Determining true glomerular filtration status in newly presenting type 2 diabetic subjects using age and sex adjustment.

OBJECTIVE: To determine age- and sex-adjusted reference ranges (ASARRs) for glomerular filtration status using data from nondiabetic subjects and to apply these to newly presenting type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: Glomerular filtration rate corrected for body surface area (cGFR) was determined using a radionuclide (51Cr-EDTA) method in 75 non-diabetic subjects (37 men, 38 women) and 219 type 2 diabetic subjects (157 men, 62 women). The 95% constant reference ranges (CRRs) were calculated as mean nondiabetic cGFR+/-1.96 SD. The 95% ASARRs were calculated by Altman's method from the nondiabetic cGFR versus age regression residuals for both male and female subjects. RESULTS: Using Altman's method, the intercepts, but not the gradients, of the cGFR versus age regressions were significantly different between male and female subjects (intercept difference [95% CI] 8.2 [1.3-15.1], gradient difference -0.4 [-1.1 to 0.3]). Fitting a common gradient, 95% ASARRs for normofiltration were found to be from 123.9 - (0.89 X age) to 181.7 - (0.89 x age) for male subjects, and from 116.0 - (0.89 X age) to 173.2 - (0.89 X age) for female subjects. The 95% CRR for normofiltration was 70.2-138.1 ml x min(-1) x (1.73 m)(-2). When applied to the diabetic cGFRs, the CRRs and ASARRs gave, respectively, 17% (37/219) versus 21% (46/219) hyperfiltrators and 83% (181/219) versus 79% (172/219) normofiltrators. Using the ASARRs, 14 normofiltrators (6 men, 8 women) were reclassified as hyperfiltrators (change [n/total n] [95% CI] 8% [14/181] [4-12]), and 5 hyperfiltrators (5 men, 0 women) were reclassified as normofiltrators (change 14% [5/37] [5-30]). CONCLUSIONS: We conclude that age and sex adjustment are essential to assess glomerular filtration status.

Adult↗
PubMed1996

Short communication: a comparison of fine and medium screens for mammography.

Intensifying screens for mammography may be categorized as fine, giving priority to image quality, or medium, achieving a lower dose at the expense of some image quality. It is important to be aware of the possible consequences of changing from a fine to a medium screen. The relative image quality and dose of four film-screen combinations (Fuji MIMA/UMMA film with Fuji HR Mammo Fine and HR Mammo Medium screens, Kodak MinRE film with Kodak MinR and MinR Medium screens) were evaluated using Leeds TOR(MAM) and Ackermann test objects. In each case, the performance of the medium screen was compared with that of the fine screen from the same manufacturer; it was not the purpose of this study to compare one manufacturer's products with the other's. Both medium screens showed measurably poorer image quality than the corresponding fine screens. The reduction in dose was only 30-40%. Careful evaluation of other dose reduction methods is recommended before changing from fine to medium screens.

Humans↗
PubMed1995

A method for estimating compressed breast thickness during mammography.

Measurements of compressed breast thickness during mammography is necessary for the calculation of breast dose. In theory, it should be possible to calculate breast thickness from the separation of images of radio-opaque markers attached to the compression paddle. Such a technique has been evaluated on two models of X-ray set using simulated and real breasts. The results show that breast thickness at a given position can be determined with an average error of about 2 mm by this method, which is likely to be adequate for dosimetry.

Breast↗
PubMed1993

Unilateral renal artery stenosis seen initially as severe and symptomatic hypokalemia. Pathophysiologic assessment and effects of surgical revascularization.

Hypokalemia is an uncommon presentation of renovascular hypertension. Although renal artery stenosis has been associated with hypokalemia secondary to hyperreninemic hyperaldosteronism, few reports have actually evaluated the pathophysiologic changes in such a patient with renovascular hypertension. We studied a patient before and after surgical revascularization who presented with severe hypertension and marked, symptomatic hypokalemia. Before surgery, the patient had excessive urinary potassium secretion, markedly increased secretion of renin after captopril stimulation, and mild secondary hyperaldosteronism. Postoperatively, the patient's blood pressure decreased moderately and the serum and urinary potassium values normalized. After revascularization, plasma renin activity both before and after captopril stimulation and serum aldosterone levels decreased markedly. These findings demonstrate that renovascular hypertension may rarely present with symptomatic hypokalemia secondary to excessive aldosterone secretion. Improvement in the renal ischemic state is accompanied by rapid correction of the metabolic disturbances associated with hyperreninemic hyperaldosteronism.

Aldosterone↗
PubMed1993

Absorption of radiolabelled soluble insulin in type 1 (insulin-dependent) diabetes: influence of subcutaneous blood flow and anthropometry.

The rate of absorption of soluble insulin, and its relationships with subcutaneous blood flow (SCBF) and patients' anthropometry, were investigated in 12 male Type 1 (insulin-dependent) diabetic patients of less than 10 yr disease duration (age range: 23-29 yr; body mass index (BMI): 22.2-30.8 kg m-2). Simultaneous assessment of the absorption of 125I-labelled soluble insulin and SCBF (99mTechnetium clearance) were performed, on separate study days, for the anterior abdominal wall, anterior mid-thigh, and the upper arm injection sites. Absorption of 125I soluble insulin, including during the lag-phase, was determined by the two- and three-parameters biexponential models description of residual radioactivity levels at the injection site. Anthropometric measurements utilized were: BMJ, ultrasonic measurement of the subcutaneous adipose tissue layer, and caliper skinfold thickness at anterior abdominal wall, biceps, triceps, anterior mid-thigh and subscapular sites. Rate-constants for absorption of soluble insulin were positively correlated with SCBF (Spearman rank coefficient (rs) = 0.33-0.55; p < 0.01-0.001). An inverse relationship was observed between the duration of the lag-phase and SCBF (rs = -0.28 - -0.54; p < 0.05-0.001). Patients' degree of adiposity was inversely correlated with the rate of soluble insulin absorption (rs = -0.24 - -0.28; p < 0.05) and SCBF (rs = -0.28 - -0.43; p < 0.05-0.001). Consequently, faster absorption of soluble insulin, with shorter lag-phase duration, was noted for the abdominal and thigh sites for non-obese (BMI > 25 kg m-2) than obese patients (BMI < 27.5 kg m-2) (p < 0.05-0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗
PubMed1992

Relationship between absorption of radiolabeled soluble insulin, subcutaneous blood flow, and anthropometry.

OBJECTIVE: To evaluate the interrelationships between the rate of absorption of soluble insulin, SCBF, and anthropometry in normal subjects. RESEARCH DESIGN AND METHODS: In 12 normal men (age range 23-30 yr, BMI 18.2-41.3 kg/m2), simultaneous assessment of the absorption of 125I-labeled soluble insulin and SCBF (99mTc clearance) was performed, on separate study days, for the anterior abdominal wall, anterior midthigh, and the upper arm sites. Each site was examined in a randomized order on two separate occasions. Absorption of 125I-soluble insulin was determined by external monitoring of residual radioactivity levels at the injection site for 6 h postinjection. Residual radioactivity level-time curves, including the characteristic early phase of slow absorption of soluble insulin (the lag phase), were described using two- and three-parameter biexponential models. Anthropometric measurements included BMI, ultrasonic measurement of the subcutaneous adipose tissue layer, and caliper skin fold thickness at the anterior abdominal wall, biceps, triceps, anterior midthigh, and subscapular sites. RESULTS: A highly significant positive relationship was observed between the rate of absorption of 125I-soluble insulin and SCBF (rS = 0.44-0.52; P < 0.01-0.001). The duration of the lag phase was inversely correlated with SCBF (rS = 0.34 - 0.51; P < 0.01-0.001). Inverse relationships also were observed for the subjects' degree of adiposity with the rate of soluble insulin absorption (rS = -0.43(-)-0.71; P < 0.001) and SCBF (rS = -0.27(-)-0.62; P < 0.05-0.001). Significantly shorter lag phase was observed for the abdominal site compared with thigh and arm injection sites (P < 0.05-0.01). CONCLUSIONS: The rate of absorption of soluble insulin, including during the lag phase, is positively correlated with SCBF. Increasing adiposity prolongs the duration of the early lag phase and reduces the rate of absorption of soluble insulin and SCBF.

Absorption↗
PubMed1991

Simultaneous determination of glomerular filtration rate and effective renal plasma flow.

A method is described for the simultaneous determination of GFR and ERPF within the normal range using a single injection of 51Cr-EDTA and 125I-OIH. Reference values of GFR (range 59-176 ml min-1) and ERPF (268-810 ml min-1) were calculated from bi-exponential analysis of curves based on multiple plasma samples. A subset of the samples (44, 120, 180 and 240 min) was used to estimate GFR by fitting a bi-exponential curve. Regression analysis demonstrated that the reference GFR value could be predicted from this four-sample estimate with a standard error of estimate (SEE) of 2.9 ml min-1, which compared favourably with methods based on mono-exponential analysis (minimum SEE = 6.3 ml min-1) or single samples (minimum SEE = 7.7 ml min-1). The effective volume of distribution of 125I-OIH calculated from the 44 min sample was used to estimate ERPF using a published equation with a SEE of 52 ml min-1. The improved precision of this simplified method for the simultaneous measurement of GFR and ERPF in the normal range will facilitate longitudinal studies in large patient groups in the evaluation of the causative factors of renal disease.

Chromium Radioisotopes↗
PubMed1991

Absorption kinetics and action profiles of subcutaneously administered insulin analogues (AspB9GluB27, AspB10, AspB28) in healthy subjects.

OBJECTIVE: The subcutaneous absorption and resulting changes in plasma insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations after subcutaneous bolus injection of three soluble human insulin analogues (AspB9GluB27, monomeric; AspB28, mixture of monomers and dimers; and AspB10, dimeric) and soluble human insulin were evaluated. RESEARCH DESIGN AND METHODS: Fasting healthy male volunteers (n = 7) were studied on five occasions 1 wk apart randomly receiving 0.6 nmol.kg-1 s.c. 125I-labeled AspB10 or soluble human insulin (Novolin R, Novo, Copenhagen); 1st study and 0.6 nmol.kg-1 s.c. 125I-labeled AspB28, AspB9GluB27 or soluble human insulin (2nd study). Residual radioactivity at the injection site was measured over 8 h with frequent venous sampling for plasma immunoreactive insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations. RESULTS: The three analogues were absorbed 2-3 times faster than human insulin. The mean +/- SE time to 50% residual radioactivity was 94 +/- 6 min for AspB10 compared with 184 +/- 10 min for human insulin (P less than 0.001), 83 +/- 8 min for AspB28 (P less than 0.005), and 63 +/- 9 min for AspB9GluB27 (P less than 0.001) compared with 182 +/- 21 min for human insulin. delta Peak plasma insulin analogue levels were significantly higher after each analogue than after human insulin (P less than 0.005). With all three analogues, the mean hypoglycemic nadir occurred earlier at 61-65 min postinjection compared with 201-210 min for the reference human insulins (P less than 0.005). The magnitude of the hypoglycemic nadir was greater after AspB9GluB27 (P less than 0.05) and AspB28 (P less than 0.001) compared with human insulin. There was a significantly faster onset and offset of responses in C-peptide and intermediary metabolite levels after the analogues than after human insulin (P less than 0.05). CONCLUSIONS: The rapid absorption and biological actions of these analogues offer potential therapeutic advantages over the current short-acting neutral soluble insulins.

3-Hydroxybutyric Acid↗
PubMed1991

Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

OBJECTIVE: To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. RESEARCH DESIGN AND METHODS: Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. RESULTS: The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and 68.9 +/- 3.5 from 2.5 h onward; and hexameric insulin 20.7 +/- 1.9 from 0 to 2 h, 45.6 +/- 5.0 from 2.5 to 5 h, and 70.6 +/- 6.3 from 5 h onward. CONCLUSIONS: Association state is a major determinant of rates of absorption of insulin and insulin analogues. The lag phase and the subsequent increasing rate of subcutaneous soluble insulin absorption can be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process.

Absorption↗
PubMed1988

Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

OBJECTIVE: To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. DESIGN: Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. SETTING: Study in normal people at a diabetes research unit and a university department of medical physics. SUBJECTS: Seven healthy male volunteers aged 20-39 not receiving any other drugs. INTERVENTIONS: After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. END POINT: To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and more dramatic hypoglycaemic effect with the insulin analogue. CONCLUSIONS: The much faster absorption from subcutaneous tissue of the disubstituted monomeric insulin analogue compared with soluble insulin suggests that the analogue may be a potential candidate for rapid insulin delivery after subcutaneous bolus injection.

Absorption↗
PubMed1983

Turnover of 131I-human spleen ferritin in plasma.

Human spleen ferritin was labelled with 131I and injected into two normal men. The labelled ferritin left the plasma rapidly. The experimental clearance curve could be fitted with accuracy into two single exponential functions. The first component, T 1/2 = 9 min, accounted for the clearance of about 90% of the labelled ferritin. Surface counting showed uptake of 131I by the liver but not by the spleen. Such a rapid plasma turnover is similar to that found after injection of tissue ferritins into experimental animals but contrasts with the slow turnover previously found for 131I-labelled human plasma ferritin. Differential clearance of isoferritins from the plasma is an important factor explaining the biochemical and immunological differences between tissue and plasma ferritins.

Adult↗