The influence of HRT on technical recall in the UK Breast Screening Programme: are pain, compression force, and compressed breast thickness contributing factors?

AIM: To investigate recall for technical reasons within the UK Breast Screening Programme, and to determine whether differences exist in those women using hormone replacement therapy (HRT), considering potential associations with reported pain, compression force used and compressed breast thickness (CBT) obtained. MATERIALS AND METHOD: A prospective cohort study of 2765 women attending for incident round breast screening appointments who were either HRT users, with a minimum of 1 year duration (n=1077), or had never used HRT (n=1688). Data were collected using technical recall records, a radiographer data-collection sheet, and a self-administered participant questionnaire. RESULTS: Sixty-eight (2.5%) participants were recalled for technical reasons of whom 28 (2.6%) were HRT and 40 (2.4%) non-HRT users. This difference was not statistically significant (p=0.80). Significant differences were found for CBT between those HRT users who were and were not recalled for technical reasons (p<0.01) and for the similar categories of non-HRT users (p=0.03). No significant differences were found for force between those HRT users who were recalled or not (p=0.73) and for the similar categories of non-HRT users (p=0.07). Similarly no significant differences were found for pain between those HRT users who were recalled or not (p=0.75) and for the similar categories of non-HRT users (p=0.73). CONCLUSION: CBT was the only variable to have both a statistically and a clinically significant relationship with technical recall.

Smoking is associated with increased hepatic lipase activity, insulin resistance, dyslipidaemia and early atherosclerosis in Type 2 diabetes.

We have studied the relationships between hepatic lipase activity, smoking, dyslipidaemia insulin resistance, and early atherosclerosis in 67 Type 2 diabetic subjects, 47 non-smokers and 20 smokers. Insulin resistance was measured using an insulin modified frequently sampled intravenous glucose tolerance test. Early atherosclerosis was assessed using high-resolution ultrasound to measure carotid intima media thickness (IMT) and an arterial ultrasonic score (AUS). Smokers had higher serum cholesterol and triglyceride, lower HDL and HDL2 cholesterol as well as increased hepatic lipase activity. They were also more insulin resistant than non-smokers. Smokers also had higher patient AUS scores. On multiple regression analysis, hepatic lipase activity emerged as the most significant variable affecting patient AUS. We suggest that smoking accentuates the dyslipidaemia of Type 2 diabetic subjects and this is associated with increased hepatic lipase activity. This may be one mechanism whereby smoking further increases the risk of cardiovascular disease in Type 2 diabetes.

Increased gene expression of plasminogen activators and inhibitors in left ventricular hypertrophy.

In the early stages of left ventricular hypertrophy (LVH) acute adaptive changes occur in the coronary vasculature as it remodels. Plasminogen activators (PAs) and inhibitors (PAIs) have the potential effects of proteolytic degradation that is relevant to tissue remodeling and angiogenesis. Our study focused on the possible roles of PAI-1, PAI-2, and uPA in tPA in myocyte hypertrophy and angiogenesis in the early and late stages of pressure overload induced left ventricular hypertrophy (LVH). We divided seventeen adult swine, weighing 24.2 +/- 6.5 kg, into four groups: control, sham-operated, early LVH and late heart failure LVH group. At surgery we placed a fixed constrictor on the ascending aorta immediately above the aortic valve. This increased LV systolic pressure from 133 +/- 15 to 193 +/- 24 mm Hg after the surgery. We subdivided the early group into groups of 3 animals each that we euthanized at 8, 24 and 72 h after operation and obtained heart samples for analysis. In the late heart failure group individual animals were euthanized at 55, 59, 62 and 72 days after the detection of congestive heart failure. We also obtained tissue samples from the control and sham-operated swine. Sections for histologic analysis were fixed in 10% buffered formalin. We isolated RNA, size fractionated it using 1% formaldehyde-agarose gel electrophoresis and then did Northern blots. The mRNAs from both PAI-1 and PAI-2 showed a remarkable increase at 8 and 24 h after acute aortic constriction and returned to control by 72 h. Regional differences showed that most of the increases were in the endocardium. Three animals in the late heart failure LVH group were determined to be in congestive heart failure at about 2 months after the onset of aortic constriction. In these animals PAI-1 and PAI-2 were increased in both the left and right ventricles but remained low in an animal of the same elevation in aortic pressure seen by the LV who did not have congestive failure. These data suggest that PA and PAI gene expressions change before morphologic changes occur in the early stages of developing LVH. Also at the time of onset of congestive heart failure this increased expression reappears. PAs and PA inhibitors mRNA levels vary in the different regions of the heart reflecting changing wall stresses. Thus, the PAs and PA inhibitors may play an important role in angiogenesis that occurs during the early stages of LVH. The increased expression in the late stage of LVH may reflect further changes in wall stresses since these animals also showed overt clinical signs of heart failure.

Association of angiotensin converting enzyme DD genotype with hypertension in diabetes.

Angiotensin converting enzyme (ACE) genotypes have been associated with hypertension in the general population. However, the relation of ACE genotype to the prevalence of hypertension in diabetic populations is less clear. This study investigated ACE genotypes in 100 patients with diabetes mellitus, of whom 41 were on anti-hypertensive medication. A significant association was found between the presence of the ACE-D allele and hypertension in both the overall diabetic group (D = 0.66, P < 0.01) and in the subset of diabetics who had non-insulin-dependent diabetes (D = 0.69, P < 0.001). There was no correlation of ACE genotype with hypertension in insulin-dependent diabetes (D = 0.57).

Gene expression in a swine model of right ventricular hypertrophy: intercellular adhesion molecule, vascular endothelial growth factor and plasminogen activators are upregulated during pressure overload.

We have investigated the molecular changes which occur during pressure overload hypertrophy of the RV in swine. Animals were banded on the pulmonary artery so that right ventricular pressure was increased two-fold. The heart was harvested at 3, 7, 24 and 72 h after surgery. Between 7 and 72 h there was evidence of muscle damage and inflammation. Northern blot experiments showed that pressure overload induced a transient increase in the expression of the immediate early genes and in the developmentally regulated atrial natriuretic factor and skeletal muscle alpha actin genes. Consistent with the histological observations of inflammation, increases in the expression of the gene for intercellular adhesion molecule, which encodes a protein involved in the binding of leukocytes by endothelial cells and myocytes, was observed between 3 and 24 h. In addition, the expression of vascular endothelial growth factor, a growth and permeability factor specific for endothelial cells was increased at 3 and 7 h of pressure overload. An increase in the expression of urokinase plasminogen activator and its inhibitors, plasminogen activator inhibitors I and II, was also observed between 3 and 24 h. This was associated with an increase in urokinase activity in the myocardial tissue. These results indicate that hypertrophy in a large mammal such as swine induces a program of gene expression similar to that previously described in rodents and suggests that up-regulation of a variety of other genes is an early response to pressure overload.

Compensatory angiogenesis during progressive right ventricular hypertrophy.

We investigated vascular adaptations occurring in progressive right ventricular hypertrophy (RVH) in adult mini pigs. Fourteen mini pigs had progressive RVH induced by implanting an inflatable cuff on the main pulmonary artery for 1-5 months and were compared to a control group (N = 11). RVH animals were divided into two groups, a moderate RVH (MH) that had RV/BW ratio increases of 20%-70% above controls and a severe hypertrophy group (SH) that had RV/BW ratio increase of 70%-117%. We measured coronary blood flow reserve (CBFR) with radiolabelled microspheres at maximal exercise and during adenosine vasodilation. Adenosine vasodilation did not decrease CBFR either regionally or transmurally in both the MH and SH groups. During exercise CBFR showed a small but significant decrease in the SH group. No intervention changed the endo/epi flow ratios. Morphometric studies showed that myocytes increased in cross sectional areas (CSA) in these hypertrophied hearts. The CSA of capillaries and arterioles and their numerical densities increased significantly in the endocardial and epicardial regions in both MH and SH groups. Capillary density showed a small but significant decrease in both MH and SH groups. We measured DNA synthesis in these hearts using tritiated thymidine labelling. We found a high labelling index in endothelial cells and a moderate labelling index in smooth muscle cells in early stages of hypertrophy. These data show that angiogenesis, observed in the morphometric studies and by DNA labelling, prevents CBFR changes during progressive RVH in the pig. Furthermore, angiogenesis is not uniform at different stages of progressive RVH.

Regional capillary and myocyte distribution in normal and exercise trained male and female rat hearts.

Adult Sprague-Dawley male and female rats were exercise trained for five months by either treadmill running or swimming. Significant differences in left ventricular regional capillary density and myocyte cross-sectional area were found. In control rats the epicardial regions had greater capillary density than endocardial regions. Endocardial myocyte cross-sectional areas were greater than those of epicardial myocytes in both sexes. Male rats had larger endocardial myocytes and larger hearts than females. After exercise training, myocyte size increased in the epicardial region but not in the endocardial region, while capillary density increased significantly only in the endocardial region. Similar changes were seen in both male and female rats with comparable degrees of exercise induced hypertrophy. These data suggest that exercise training "normalizes" the distribution of capillaries in the myocardium. Capillary density increased only in the regions where myocyte cross-sectional area did not increase. Further, the effects of exercise on male and female rat hearts is not different when the degree of exercise induced hypertrophy is similar.

Cardiac vasculature and flow during pressure-overload hypertrophy.

The effects of pressure-overload hypertrophy (H) on myocardial blood flow and microvasculature were studied in the porcine left ventricle. Hypertrophy was produced in nine adult pigs by an aortic cuff constriction of the ascending aorta. Eight pigs served as controls. After 30 days the aortic cuff was released, and the hypertrophy group was studied 1 day postrelease. The degree of hypertrophy, determined by left ventricular-to-body weight ratio, was 45%. With hypertrophy, left ventricular blood flows were normal at rest. During exercise with adenosine infusion, myocardial blood flow to the endomyocardium was reduced compared with the control (C) group (H = 4.02 +/- 0.35, P less than 0.05; C = 5.33 +/- 0.41 ml X min-1 X g-1). Minimal coronary vascular resistance in the endomyocardium was increased during exercise with adenosine in the hypertrophy group compared with the control group. Anatomic studies revealed that hypertrophy causes a reduction in the endomyocardial capillary density (H = 1,654 +/- 168, P less than 0.025; C = 2,168 +/- 106, no./mm2) with a similar trend noted for the transmural arteriolar density. Arteriolar media wall cross-sectional area was unaffected by the pressure overload. These results indicate that changes in the vascular bed do not parallel myocyte growth during pressure-overload hypertrophy. The resultant anatomic imbalance compromises endomyocardial flow, making this region vulnerable to ischemia.

Exercise-induced cardiac hypertrophy: a correlation of blood flow and microvasculature.

The effects of exercise conditioning on the myocardium were studied in seven instrumented pigs strenuously exercised for 12 wk by treadmill running. Data were compared with eight instrumented untrained pigs. O2 consumption measured during maximum exercise effort was significantly elevated in the trained pigs (71.7 +/- 4.0 vs. 56.3 +/- 3.0 ml X ml-1 X kg-1). Absolute right and left ventricular mass increased by 20 and 13%, respectively, in response to exercise. Myocyte cross-sectional area increased by 21% in the trained hearts compared with the untrained hearts. Transmural left ventricular myocardial blood flow (ml X min-1 X g-1) was not significantly different at rest, during maximum exercise, or during exercise with adenosine infusion. However, training caused an elevation of the regional epicardial blood flow noted during exercise and exercise with adenosine. In the trained pigs mean aortic pressure during maximum exercise with adenosine infusion was not significantly different compared with untrained pigs. Coronary resistance during exercise with adenosine infusion was the same in both animal groups. In the trained group capillary numerical (no./mm2) and length (mm/mm3) densities were reduced, whereas arteriolar numerical and length densities were significantly increased compared with the untrained group. Measurements of capillary luminal surface density (mm2/mm3) in the trained group were unchanged compared with the untrained group. These results suggest that strenuous exercise does not stimulate the production of new capillaries, but this is modified by the ability of existing capillaries to increase their luminal surface area to parallel increases in myocyte growth. The arteriolar data suggest that exercise promotes the formation of new arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)

Selection of media for the isolation of common bacterial L-phase organisms from a clinical specimen.

The L-phase of 13 bacteria commonly associated with disease were induced by penicillin and inoculated into various solid and broth media; their growth was recorded for a period of 14 days. Plates containing highly purified agar and sucrose as the stabilizing agent and those incubated under aerobic conditions gave the best results. Magnesium seems to be necessary for growth in broth media on primary isolation, although it may not be necessary on multiple transfers after a more stable state has been reached. Growth in broth media is much more difficult to achieve. Reversion is aided by using a higher concentration of agar in plates, by decreasing the sucrose concentration, and by omitting the antibiotics and horse serum. A procedure has been outlined for the routine culture and identification of L-phase organisms from a clinical specimen.