Measurement of changes in uterine and fibroid volume during treatment of heavy menstrual bleeding (HMB).

STUDY QUESTION: Does application of an unbiased method for analysis of magnetic resonance (MR) images reveal any effect on uterine or fibroid volume from treatment of heavy menstrual bleeding (HMB) with three 12-week courses of the selective progesterone receptor modulator ulipristal acetate (SPRM-UPA)? SUMMARY ANSWER: Application of an unbiased method for analysis of MR images showed that treatment of HMB with SPRM-UPA was not associated with a significant reduction in the volume of the uterus or in the volume of uterine fibroids. WHAT IS KNOWN ALREADY: SPRM-UPA shows therapeutic efficacy for treating HMB. However, the mechanism of action (MoA) is not well understood and there have been mixed reports, using potentially biased methodology, regarding whether SPRM-UPA has an effect on the volume of the uterus and fibroids. STUDY DESIGN SIZE DURATION: In a prospective clinical study (with no comparator), 19 women with HMB were treated over a period of 12 months with SPRM-UPA and uterine and fibroid size were assessed with high resolution structural MRI and stereology. PARTICIPANTS/MATERIALS SETTING METHODS: A cohort of 19 women aged 38-52 years (8 with and 11 without fibroids) were treated with three 12-week courses of 5 mg SPRM-UPA given daily, with four weeks off medication in-between treatment courses. Unbiased estimates of the volume of uterus and total volume of fibroids were obtained at baseline, and after 6 and 12 months of treatment, by using the Cavalieri method of modern design-based stereology in combination with magnetic resonance imaging (MRI). MAIN RESULTS AND THE ROLE OF CHANCE: Bland-Altman plots showed good intra-rater repeatability and good inter-rater reproducibility for measurement of the volume of both fibroids and the uterus. For the total patient cohort, two-way ANOVA did not show a significant reduction in the volume of the uterus after two or three treatment courses of SPRM-UPA (P = 0.51), which was also the case when the groups of women with and without fibroids were considered separately (P = 0.63). One-way ANOVA did not show a significant reduction in total fibroid volume in the eight patients with fibroids (P = 0.17). LIMITATIONS REASONS FOR CAUTION: The study has been performed in a relatively small cohort of women and simulations that have subsequently been performed using the acquired data have shown that for three time points and a group size of up to 50, with alpha (Type I Error) and beta (Type II Error) set to 95% significance and 80% power, respectively, at least 35 patients would need to be recruited in order for the null hypothesis (that there is no significant reduction in total fibroid volume) to be potentially rejected. WIDER IMPLICATIONS OF THE FINDINGS: The imaging protocol that we have developed represents a generic paradigm for measuring the volume of the uterus and uterine fibroids that can be readily incorporated in future studies of medical treatments of HMB. In the present study, SPRM-UPA failed to produce a significant reduction in the volume of the uterus or the total volume of fibroids (which were present in approximately half of the patients) after either two or three 12-week courses of treatment. This finding represents a new insight in respect of the management of HMB using treatment strategies that target hormone-dependence. STUDY FUNDING/COMPETING INTERESTS: The UPA Versus Conventional Management of HMB (UCON) trial was funded by the EME Programme (Medical Research Council (MRC) and National Institutes of Health Research (NIHR)) (12/206/52). The views expressed in this publication are those of the authors and not necessarily those of the Medical Research Council, National Institute for Health Research, or Department of Health and Social Care.Medical Research Council (MRC) Centre grants to the Centre for Reproductive Health (CRH) (G1002033 and MR/N022556/1) are also gratefully acknowledged. H.C. has clinical research support for laboratory consumables and staff from Bayer AG and provides consultancy advice (All paid to Institution) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc., and Myovant Sciences GmbH. H.C. has received royalties from UpToDate for an article on abnormal uterine bleeding. L.W. has received grant funding from Roche Diagnostics (Paid to Institution). All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: The study reported here is an embedded mechanism of action study (no comparator) within the UCON clinical trial (registration ISRCTN: 20426843).

Incidental finding of large pneumothorax on Cardiac MR scan.

BACKGROUND: We believe this is the first case report of a pneumothorax being identified using cardiac magnetic resonance imaging. This case also illustrates the haemodynamic effect a large pneumothorax can have on right ventricular filling in diastole. CASE PRESENTATION: A 26-year-old attended for an interval follow up Cardiac Magnetic Resonance (CMR) of his thoracic aorta after a thoracic co-arctation repair aged 3. He was found to have an incidental large pneumothorax by the reporting cardiology fellow which was confirmed by the on-call radiologist. The pneumothorax was most notable for its compression of the right ventricle in diastole. Although the patient had worrying features on CMR imaging, he remained clinically stable and a conservative approach to management saw the pneumothorax resolve after a 3 week period. CONCLUSIONS: Pneumothoraces are important, potentially life threatening conditions. Although very rarely identified on MR imaging, radiographers and reporting doctors should be aware of their key features. This case serves to identify not only the abnormal lung parenchymal features but also the striking compressional effect of the pneumothorax on the right ventricle in diastole. Indeed we believe this is the first case report of a pneumothorax identified on CMR imaging.

Iterative reconstruction and individualized automatic tube current selection reduce radiation dose while maintaining image quality in 320-multidetector computed tomography coronary angiography.

AIM: To assess the effect of two iterative reconstruction algorithms (AIDR and AIDR3D) and individualized automatic tube current selection on radiation dose and image quality in computed tomography coronary angiography (CTCA). MATERIALS AND METHODS: In a single-centre cohort study, 942 patients underwent electrocardiogram-gated CTCA using a 320-multidetector CT system. Images from group 1 (n = 228) were reconstructed with a filtered back projection algorithm (Quantum Denoising Software, QDS+). Iterative reconstruction was used for group 2 (AIDR, n = 379) and group 3 (AIDR3D, n = 335). Tube current was selected based on body mass index (BMI) for groups 1 and 2, and selected automatically based on scout image attenuation for group 3. Subjective image quality was graded on a four-point scale (1 = excellent, 4 = non-diagnostic). RESULTS: There were no differences in age (p = 0.975), body mass index (p = 0.435), or heart rate (p = 0.746) between the groups. Image quality improved with iterative reconstruction and automatic tube current selection [1.3 (95% confidence intervals (CI): 1.2-1.4), 1.2 (1.1-1.2) and 1.1 (1-1.2) respectively; p < 0.001] and radiation dose decreased [274 (260-290), 242 (230-253) and 168 (156-180) mGy cm, respectively; p < 0.001]. CONCLUSION: The application of the latest iterative reconstruction algorithm and individualized automatic tube current selection can substantially reduce radiation dose whilst improving image quality in CTCA.

Cardiac and coronary CT comprehensive imaging approach in the assessment of coronary heart disease.

Cardiac CT is a rapidly advancing technology. Non-invasive CT coronary angiography is an established technique for assessing coronary heart disease with accuracy similar to invasive coronary angiography. CT myocardial perfusion imaging can now identify perfusion defects in animal models and humans. MRI is the current 'gold standard' for the assessment of myocardial viability, but it is now also possible to assess delayed enhancement by CT. This has led to the possibility of a 'one-stop shop' for cardiovascular imaging that would provide information on anatomy, function, perfusion and viability in one rapid diagnostic test at a radiation dose equivalent to contemporary nuclear medicine imaging. This review discusses the current status of 'one-stop shop' cardiac CT assessment, clinical utility and directions for future research.

Limited clinical utility of CT coronary angiography in a district hospital setting.

BACKGROUND: Studies have demonstrated considerable accuracy of multi-slice CT coronary angiography (MSCT-CA) in comparison to invasive coronary angiography (I-CA) for evaluating coronary artery disease (CAD). The extent to which published MSCT-CA accuracy parameters are transferable to routine practice beyond high-volume tertiary centres is unknown. AIM: To determine the accuracy of MSCT-CA for the detection of CAD in a Scottish district general hospital. DESIGN: Prospective study of diagnostic accuracy. METHOD: One hundred patients with suspected CAD recruited from two Glasgow hospitals underwent both MSCT-CA (Philips Brilliance 40 × 0.625 collimation, 50-200 ms temporal resolution) and I-CA. Studies were reported by independent, blinded radiologists and cardiologists and compared using the AHA 15-segment model. RESULTS: Of 100 patients [55 male, 45 female, mean (SD) age 58.0 (10.7) years], 59 and 41% had low-intermediate and high pre-test probabilities of significant CAD, respectively. Mean (SD) heart rate during MSCT-CA was 68.8 (9.0) bpm. Fifty-seven per cent of patients had coronary artery calcification and 35% were obese. Patient prevalence of CAD was 38%. Per-patient sensitivity, specificity, positive and negative (NPV) predictive values for MSCT-CA were 92.1, 47.5, 52.2 and 90.6%, respectively. NPV was reduced to 75.0% in the high pre-test probability group. Specificity was compromised in patients with sub-optimally controlled heart rates, calcified arteries and elevated BMI. CONCLUSION: Forty-Slice MSCT-CA has a high NPV for ruling out significant CAD when performed in a district hospital setting in patients with low-intermediate pre-test probability and minimal arterial calcification. Specificity is compromised by clinically appropriate strategies for dealing with unevaluable studies. Effective heart rate control during MSCT-CA is imperative. National guidelines should be utilized to govern patient selection and direct MSCT-CA reporter training to ensure quality control.

Colour Doppler imaging of the ocular circulation in diabetic retinopathy.

PURPOSE: To measure blood flow velocity in the ophthalmic artery (OA) and central retinal artery (CRA) in patients with diabetic retinopathy. SUBJECTS AND METHODS: 62 age-matched subjects divided into 3 groups: nondiabetic controls (n=17); diabetics with no clinical retinopathy or background changes (n=24); diabetics with either pre-proliferative or proliferative retinopathy (n=21). Colour Doppler imaging was performed on supine patients by one masked observer using the Acuson 128 machine. RESULTS: There was a statistically significant (p<0.05) decrease in both the peak systolic velocity (PSV 0.073 m/s) and end diastolic velocity (EDV 0.014 m/s) of the central retinal artery in the pre-proliferative/proliferative group compared to the no retinopathy/background retinopathy group (PSV 0.096 m/s, EDV 0.024 m/s) and the control group (PSV 0.142 m/s, EDV 0.029 m/s). The resistance index of the ophthalmic artery was significantly increased in both the preproliferative/proliferative (0.81) and the no retinopathy/background group (0.81) compared to controls (0.72). CONCLUSION: Reduced blood flow velocity was found in the CRA of diabetic patients and appeared to become further reduced with the progression of retinopathy. This suggests that monitoring with Colour Doppler imaging may have predictive power in identifying those at greatest risk of developing sight threatening proliferative disease. The resistance index of the OA was increased in diabetics compared to controls.

Color Doppler imaging in untreated high- and normal-pressure open-angle glaucoma.

PURPOSE: To evaluate ocular blood flow velocity indices in untreated primary open-angle glaucoma (POAG) and normal pressure glaucoma (NPG). METHODS: Twenty-five untreated patients with NPG, 23 untreated patients with POAG, and 26 age-matched normal control subjects underwent color Doppler imaging for the measurement of blood flow velocity in the central retinal and ophthalmic arteries. Neither the patients nor the control subjects were using systemic beta-blockers or calcium channel blockers. After log transformation of non-normal data, group differences were compared with a one-way analysis of variance followed by unpaired t-test with the Bonferroni correction. Statistical significance was set at P < 0.05. RESULTS: The central retinal artery end diastolic velocity was significantly lower in patients with POAG than in normal subjects. The ophthalmic artery peak systolic velocity (PSV) was significantly greater in patients with POAG than in those with NPG and normal subjects. The resistance index (RI) of both the ophthalmic and central retinal arteries was significantly greater in patients with POAG than in normal subjects, and the central retinal artery RI was significantly greater in those with NPG than in normal subjects. Systemic pulse pressure and systolic blood pressure were significantly greater in patients with POAG compared with normal subjects. Multiple regression analysis showed a significant relation between ophthalmic artery PSV and intraocular pressure (but not with any of the cardiovascular parameters) in the POAG group. Chi-square analysis found significantly more systemic vascular disease in patients with NPG and POAG compared with that of normal subjects. CONCLUSIONS: There was an increased resistance to blood flow in the central retinal artery of untreated patients with NPG and POAG and also in the ophthalmic artery of patients with POAG. The ophthalmic artery peak systolic velocity was elevated in untreated patients with POAG. Altered ocular circulation (with different patterns of presentation) appears to be common to patients with NPG and patients with POAG.

Colour Doppler imaging in giant cell (temporal) arteritis: serial examination and comparison with non-arteritic anterior ischaemic optic neuropathy.

The ophthalmological manifestations of giant cell arteritis (GCA) present a difficult diagnostic and management problem to the ophthalmologist. The orbital circulation is frequently involved in the disease process. The effects of GCA on orbital blood flow assessed by colour Doppler imaging (CDI) were investigated in this study. Serial CDI examinations of the orbital blood vessels were performed (at presentation, 2 days, 1 week and at 1 month) on 7 patients with GCA. CDI examination at presentation was also performed on 4 patients with non-arteritic anterior ischaemic optic neuropathy (AION) for comparison. Blood flow could not be detected in up to three arteries in the affected (ipsilateral) orbit of 6 GCA patients at presentation. Five of these patients were also found to have undetectable blood flow in the posterior ciliary arteries of the contralateral orbit. Serial CDI examination revealed blood flow alterations in arteritic patients despite treatment. Return of blood flow to normal was slow, and related to the clinical features. By contrast, only 1 of the patients with non-arteritic AION showed undetectable blood flow in a posterior ciliary artery. GCA leads to widespread and prolonged alterations in orbital blood flow. CDI allows the detection and monitoring of such alterations in orbital blood flow, which correlate with the clinical features of GCA. Serial CDI examinations in GCA may be used to aid management decisions.

Measurement of ocular blood flow velocity using colour Doppler imaging in low tension glaucoma.

The purpose of this study was to compare the velocity of blood flow and vascular resistance measured by colour Doppler imaging in the ophthalmic and central retinal arteries in 34 eyes of 34 patients (mean age 68.1 years) with low tension glaucoma (LTG) and 17 eyes of 17 age-matched normal controls (mean age 65.2 years). The Acuson 128 machine (using a 7.5 MHz probe) was used to measure peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistive index (RI). The EDV of the ophthalmic artery (OA) in the LTG was significantly (p = 0.04) less than in the normal control group. There was a significant (p = 0.02) increase in the vascular RI of both the OA and central retinal artery in the LTG group compared with the normal controls. The OA RI increased with age (r = 0.61, p = 0.0001), and the OA EDV decreased with age (r = -0.50, p = 0.003), in the LTG group but not in the normal control group. The results suggest an increased resistance to blood flow in the ophthalmic and central retinal arteries of LTG patients.

Color Doppler ultrasound of orbital and optic nerve blood flow: effects of posture and timolol 0.5%.

Color Doppler ultrasound allows simultaneous imaging with real-time ultrasound and superimposed color-coded vascular flow, allowing visualization of vessels previously beyond the resolution of conventional imaging, such as those in the orbit. With this technique, 20 healthy volunteers were studied. Three regional vessels named 1, 2, and 3 were identified. No significant difference in maximum or minimum blood velocity or resistive index was detected between vessels 1 and 2, although significant differences were noted between both these vessels and vessel 3 (P less than 0.01 and P less than 0.001, respectively). These regional variations are unaffected by small but significant rises in pulse (P less than 0.05) and diastolic blood pressure (P less than 0.01) induced by postural change. No significant change within each vessel was recorded in response to posture, reflecting autoregulation within these vessels. Using a similar technique, 10 healthy volunteers were studied at baseline and at 2 hr and 3 d following the unilateral instillation of 0.5% timolol eye drops. A fall in resistive index was recorded in vessel 3 for both eyes (P less than 0.05, timolol administered eye; P less than 0.01 timolol-free eye). This effect was independent of any simultaneous fall in intraocular pressure that occurred only in the eye receiving timolol drops (P less than 0.01). These results support the presence of B receptors in the vessels at the optic nerve head (vessel 3). A fall in resistive index should not compromise the blood supply in this region, and may even increase it.(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler echocardiography in elderly patients with ejection systolic murmurs.

Thirty-nine elderly patients, mean age 77 years (range 65 to 96), with ejection systolic murmurs were studied to evaluate the functional significance of these murmurs. Subjects were evaluated clinically, by 2-D echocardiography, and by a full Doppler echocardiography study. Good quality Doppler signals were obtained in 35 subjects. Mitral regurgitation was found to be the only significant valvular lesion in 6 patients (17%). Doppler gradients in systole across the aortic valve were less than 30 mmHg in 28 subjects (80%) and were considered not significant. Gradients of greater than 30 mmHg representing significant aortic stenosis were found in 7 subjects (20%). The clinical sensitivity in detecting significant aortic stenosis was 44% and specificity was 81%. Doppler evidence of significant aortic stenosis was found in a substantial proportion of these elderly subjects. Neither clinical assessment nor 2-D echocardiography can be relied on to exclude this condition.

The effect of habitual sustained endurance exercise on cardiac structure and function.

We performed echocardiographic evaluation of 20 male veteran endurance runners (mean age 56 +/- 7 years) and compared them with a group of age-matched controls. All the runners had run at least 25 miles per week for more than 25 years. Although only four athletes showed voltage ECG evidence of left ventricular hypertrophy, using echocardiography, 10 athletes had evidence of left ventricular hypertrophy. Thus electrocardiography is insufficiently sensitive to detect LVH in this group (10%). Left ventricular posterior wall thickness and left ventricular mass were significantly greater in the athletes, the difference becoming more marked when LV mass was corrected for body surface area and, consequently, the wall thickness: cavity diameter ratio was increased (P less than 0.04). There was no difference between the two groups in left ventricular performance and no correlation between left ventricular mass and running ability. Thus, veteran runners develop structural cardiac changes similar to younger power-trained athletes and do not show characteristics normally expected of 'volume overload' which is thought to occur in running.

Acute metabolic effects of exercise in bodybuilders using anabolic steroids.

Four male bodybuilders who had started taking anabolic steroids were monitored during exercise. Most metabolic indicators were similar to bodybuilders not taking steroids; i.e. metabolic acidosis with little change in glucose. However, there is a marked elevation of creatine kinase.

Vibration perception thresholds in 279 diabetic patients.

Generalised peripheral neuropathy is a well recognised complication of diabetes mellitus and early detection is important in order that morbidity can be reduced by interventional therapy at an early stage. Since nerve conduction studies are not a feasible option in a busy diabetic clinic, an alternative technique of detection, superior to clinical examination, is beneficial. In this study vibration perception thresholds were measured in 279 diabetic outpatients. Seventy-eight patients (28%) had abnormal results but only 35 (13%) had clinical evidence of neuropathy. While nerve conduction studies remain the most sensitive technique to detect nerve dysfunction, vibration perception threshold determination is a useful screening test to detect subclinical peripheral nerve dysfunction in a routine diabetic outpatient clinic.

Lipoprotein analysis in bodybuilders.

The use of anabolic steroids to augment athletic performance is widespread. It is known that these drugs can adversely affect lipoproteins in normal volunteers, leading to increased cholesterol and low density lipoprotein and depressed high density lipoprotein. It has been shown that endurance type exercise can lead to beneficial effects on lipoproteins but the effects of power exercise are less clear-cut and made more difficult to interpret by prior anabolic steroid use. This paper details the lipoprotein results in 24 subjects, eight sedentary controls, eight non-steroid and eight steroid using bodybuilders. The results revealed no significant difference between sedentary controls and non-steroid bodybuilders suggesting that this form of training does not cause beneficial effects on lipoproteins. However, the steroid-using groups had higher cholesterol and low density lipoprotein, with lower high density lipoprotein, high density lipoprotein2, high density lipoprotein3 and high density lipoprotein2/high density lipoprotein3 ratios compared to the other two groups. The long-term effects of such results may be an increased risk of atherosclerosis and requires long-term follow-up.

A case of intravenous and oral mefenamic acid poisoning.

A 22 year old heroin addict was admitted with tonic-clonic seizures, confusion and agitation 10 hours after taking mefenamic acid 5 grams orally and 2.25 grams intravenously. This appears to be the first recorded case of intravenous mefenamic acid abuse and, although not fatal, is a cause of concern. This is a commonly used drug and its seizure inducing potential is well recognised. It may therefore be worthwhile considering the possibility of intravenous abuse of mefenamic acid in heroin addicts admitted with confusion or seizures.