Recurrent miscarriage: do professionals adhere to their guidelines.

STUDY QUESTION: Is the actual care for recurrent miscarriage in clinical practice in accordance with 23 guideline-based quality indicators? SUMMARY ANSWER: The accordance of actual care with the guidelines was poor and there is evident room for improvement. WHAT IS KNOWN ALREADY: Evidence-based guidelines are important instruments to improve quality of care, but implementation of guidelines is often problematic. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study was performed within a 12-month period (2006) in nine departments of Obstetrics and Gynaecology in the Netherlands. PARTICIPANTS, SETTING, METHODS: Five hundred and thirty women with recurrent miscarriage were included. Actual care was assessed with 23 guideline-based quality indicators (covering diagnostics, therapy and counselling) by calculating per indicator the percentage of women for whom the indicator was followed. Thereafter we did multilevel analyses, to relate the adherence to the indicator to determinants of women, professionals and hospitals. MAIN RESULTS AND THE ROLE OF CHANCE: Homocysteine and antiphospholipid antibodies were determined in 39 and 47%, respectively. Thrombophilia screening (54%) and karyotyping (50%) were offered to women regardless of their underlying risk for inherited thrombophilia or chromosome abnormalities. Higher maternal age at the time of presentation and a lower number of preceding miscarriages were improperly used to decide on diagnostic tests and were both associated with lower guideline adherence by professionals. Professionals with a subspecialization in recurrent miscarriage performed better standard care, i.e. screening for antiphospholipid antibodies and homocysteine, but also showed overuse of diagnostics in women at low risk of inherited thrombophilia. LIMITATIONS, REASONS FOR CAUTION: Retrospective cohort study. WIDER IMPLICATIONS OF THE FINDINGS: Quality indicators used will enable measurement of quality of care. STUDY FUNDING: The study was funded by The Netherlands Organisation for Health Research and Development (ZonMw) (Grant no. 94517005). None of the authors has any conflict of interest to declare.

High field carotid vessel wall imaging: a study on reproducibility.

PURPOSE: Currently, a multi-contrast protocol, including a combination of five MR-sequences is used as reference standard for morphologic imaging and quantitative measurements of the carotid artery vessel wall. The purpose of this study is to investigate the scan-rescan reproducibility together with intra- and inter-observer reproducibility of each of the five MR-sequences. METHODS: Twenty healthy volunteers (55% male, mean age=26 years) underwent repeated MR-examinations (3T-Philips-MRI) of the left carotid artery vessel wall with five sequences; T1-TFE, T2-TSE, PD-TSE, T1-TSE and 3D TOF. A standard phased-array coil with two flexible elements of 14cm×17cm was used to obtain nine transverse imaging sections of the left carotid artery with identical in-plane resolution (0.46mm×0.46mm). Reproducibility analysis was performed in 3 slices of the common carotid artery for all sequences. RESULTS: For, scan-rescan reproducibility, intra class correlation coefficients (ICC) were excellent for all sequences and ranged from 0.79 to 0.95. The intra-observer ICC ranged from 0.89 to 0.98 and the inter-observer ICC ranged from 0.84 to 0.96, for both lumen and vessel wall assessment. CONCLUSIONS: By high field MR imaging, vessel wall and lumen area of the carotid artery can be assessed with excellent scan-rescan, intra- and inter-observer reproducibility for all five sequences.

Misoprostol and termination of pregnancy: is there a need for ultrasound screening in a general population to assess the risk for adverse outcome in cases of uterine anomaly?

PURPOSE AND METHODS: We reviewed the existing literature on medical termination of pregnancy in cases of congenital uterine malformation. Is medical termination of pregnancy safe in the presence of a uterine anomaly? Can termination of pregnancy still be performed when information concerning the presence of congenital uterine malformation is not available? RESULTS: The risk of adverse outcome, i.e. uterine rupture, was high in class 2 uterine anomalies, whereas the risks in classes 3-6 were negligible. However, the very low incidence of class 2 anomalies in pregnant women results in a calculated risk of uterine rupture in medical termination of pregnancy on the basis of this anomaly of 1 in 300,000 pregnancies. Ultrasound scanning is of limited diagnostic value to diagnose congenital uterine malformations. CONCLUSIONS: The implications of uterine anomalies are not an argument in the discussion whether to use misoprostol for termination of pregnancy in developing countries with scarce diagnostics tools.

Relation between regional and global systolic function in patients with ischemic cardiomyopathy after beta-blocker therapy or revascularization.

BACKGROUND: To assess the relationship between improved regional and global myocardial function in patients with ischemic cardiomyopathy in response to beta-blocker therapy or revascularization. MATERIALS AND METHODS: Cardiovascular magnetic resonance (CMR) was performed in 32 patients with ischemic cardiomyopathy before and 8 +/- 2 months after therapy. Patients were assigned clinically to beta-blocker therapy (n = 20) or revascularization (n = 12). CMR at baseline was performed to assess regional and global LV function at rest and under low-dose dobutamine. Wall thickening was analyzed in dysfunctional, adjacent, and remote segments. Follow-up CMR included rest function evaluation. RESULTS: Augmentation of wall thickening during dobutamine at baseline was similar in dysfunctional, adjacent and remote segments in both patient groups. Therefore, baseline characteristics were similar for both patient groups. In both patient groups resting LV ejection fraction and end-systolic volume improved significantly (p < 0.05) at follow-up. Stepwise multivariate analysis revealed that improvement in global LV ejection fraction in the beta-blocker treated patients was significantly related to improved function of remote myocardium (p < 0.05), whereas in the revascularized patients improved function in dysfunctional and adjacent segments was more pronounced (p < 0.05). CONCLUSION: In patients with chronic ischemic LV dysfunction, beta-Blocker therapy or revascularization resulted in a similar improvement of global systolic LV function. However, after beta-blocker therapy, improved global systolic function was mainly related to improved contraction of remote myocardium, whereas after revascularization the dysfunctional and adjacent regions contributed predominantly to the improved global systolic function.

Temporal endosonographic evaluation of anal sphincter integrity after primary repair for obstetric ruptures: a case for specific training of obstetricians.

OBJECTIVE: To evaluate primary repaired obstetric lesions of the anal sphincter complex on anal endo-ultrasound within a few days and 8 weeks after primary repair and to investigate in this way the influence of suboptimal woundhealing on the final anatomical result. Furthermore to investigate the relation between faecal incontinence and sphincter defects. DESIGN: A prospective cohort study. Setting The obstetric clinic and coloproctology outpatient clinic of the Zaans Medical Centre in Zaandam, the Netherlands. Subjects A cohort of 32 consecutive women with primary surgically repaired 3B, 3C or 4th degree anal sphincter defect after vaginal delivery. MAIN OUTCOME MEASURES: Appearance of the anal sphincter complex on anal endo-ultrasound within a few days week and 8 weeks after primary surgical repair, i.e. first and second ultrasound, respectively. Evaluation of anal continence, using the Vaizey incontinence score, at second ultrasound. RESULTS: No major wound breakdown was seen and four women had superficial, skin related wound problems. Twenty-eight women (87.5%) had a repaired external anal sphincter on the first and the second ultrasound. Of four external anal sphincter defects on first ultrasound one defect was not present on second ultrasound. The internal sphincter showed a defect on first ultrasound in 11 women and this was still present in 10 on second ultrasound. A total of 11 women had a persisting anal sphincter defect (external, internal or in combination). Mean Vaizey scores were significantly higher in women with a persisting sphincter defect (EAS, IAS or in combination) than in women with no sphincter defects, 2.3 and 0.4 respectively (95% CI 0.1-3.6, P = 0.04). CONCLUSION: Anal endo-ultrasound may be used for early evaluation of surgical repair of anal sphincter lesions after vaginal delivery. Persisting defects in the anal sphincters, in this series not because of major wound breakdown, can be explained by inadequate surgical repair.

Does a 5500-km swim trial stimulate early sexual maturation in the European eel (Anguilla anguilla L.)?

The catadromous European eel (Anguilla anguilla L.) undertakes a 6000-km spawning migration from its freshwater habitats to the Sargasso Sea. In large Blazka swim tunnels of 127 l, the physiological effect of such a prolonged swimming performance on sexual maturation in adult female eels was investigated. Two groups of eels were placed in swim tunnels for 173 days, one group was able to swim at 0.5 body lengths/second (Swim group) covering a distance of c. 5500-km over the experimental period, and one group kept in static (End Control group). A control group was sampled at the start of the experiment in order to determine the initial stage of reproductive development (Initial Control group). At the end of the swim trial, the maturation parameters 11-ketotestosterone, pituitary levels of LH and plasma levels of estradiol were higher (although not significantly) in the Swim compared to the End Control group. In addition, no significant differences were observed in most measured morphometric and reproductive parameters, including eye-index, gonadosomatic index, hepatosomatic index, and plasma levels of vitellogenin, cortisol and melanophore-stimulating hormone (MSH). Also, pituitary levels of both MSH, and adrenocorticotropic hormone (ACTH) were unaffected. In contrast, the oocyte diameter was found to be significantly higher in the Swim compared to the End Control group. Based on these observations we conclude that a period of prolonged swimming might be a physiological stimulus necessary for the onset of maturation in the European eel.

Right ventricular hypertrophy and diastolic dysfunction in arterial switch patients without pulmonary artery stenosis.

OBJECTIVE: To assess pulmonary flow dynamics and right ventricular (RV) function in patients without significant anatomical narrowing of the pulmonary arteries late after the arterial switch operation (ASO) by using magnetic resonance imaging (MRI). METHODS: 17 patients (mean (SD), 16.5 (3.6) years after ASO) and 17 matched healthy subjects were included. MRI was used to assess flow across the pulmonary trunk, RV systolic and diastolic function, and RV mass. RESULTS: Increased peak flow velocity (>1.5 m/s) was found across the pulmonary trunk in 14 of 17 patients. Increased RV mass was found in ASO patients: 14.9 (3.4) vs 10.0 (2.6) g/m2 in normal subjects (p<0.01). Delayed RV relaxation was found after ASO: mean tricuspid valve E/A peak flow velocity ratio = 1.60 (0.96) vs 1.92 (0.61) in normal subjects (p = 0.03), and E-deceleration gradients = -1.69 (0.73) vs -2.66 (0.96) (p<0.01). After ASO, RV mass correlated with pulmonary trunk peak flow velocity (r = 0.49, p<0.01) and tricuspid valve E-deceleration gradients (r = 0.35, p = 0.04). RV systolic function was well preserved in patients (ejection fraction = 53 (7)% vs 52 (8)% in normal subjects, p = 0.72). CONCLUSIONS: Increased peak flow velocity in the pulmonary trunk was often observed late after ASO, even in the absence of significant pulmonary artery stenosis. Haemodynamic consequences were RV hypertrophy and RV relaxation abnormalities as early markers of disease, while systolic RV function was well preserved.

Measurement of the Michel parameter rho in muon decay.

The TWIST Collaboration has measured the Michel parameter rho in normal muon decay, mu(+)--> e(+)nu(e)nu (mu). In the standard model, rho = 3/4. Deviations from this value imply mixing of left- and right-handed muon and electron couplings. We find rho=0.750 80+/-0.000 32(stat) +/- 0.000 97(syst) +/- 0.000 23, where the last uncertainty represents the dependence of rho on the Michel parameter eta. This result sets new limits on the W(L)-W(R) mixing angle in left-right symmetric models.

Multisequence magnetic resonance imaging study of neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To investigate the relationship between magnetization transfer imaging (MTI), diffusion-weighted imaging (DWI), proton magnetic resonance spectroscopy (H-MRS), and T2 relaxometry findings in patients with primary neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: The study group consisted of 24 female patients (mean age 36 years [range 23-65]) who had had a variety of neuropsychiatric symptoms that were judged to be due to NPSLE according to the criteria of the American College of Rheumatology. Patients with current active disease were excluded from participation. Quantitative MTI, DWI, H-MRS, and T2 relaxometry data were acquired in all patients, and the correlation coefficients were calculated. RESULTS: MTI results reflecting a decrease in homogeneity of cerebral parenchyma correlated significantly with H-MRS results representing axonal damage. MTI results also correlated significantly with DWI results reflecting increased diffusivity in the cerebral parenchyma. Finally, MTI results reflecting decreased cerebral homogeneity correlated significantly with increased T2 relaxation time, associated with either edema or gliosis. Increased T2 relaxation time correlated significantly with DWI results reflecting increased diffusivity. With the exception of the correlation between H-MRS and MTI findings, there was no significant correlation between H-MRS results and any other parameter. CONCLUSION: The selected study parameters represent different biologic features in the human brain and can be informative with regard to different pathologic processes in NPSLE. The demonstrated associations between MTI, DWI, H-MRS, and T2 data in patients with a history of NPSLE suggest that there is one pathogenesis and/or common neuropathologic outcome in NPSLE despite differences in clinical presentation.

Mitral valve regurgitation: accurate blood flow quantification with MRI.

BACKGROUND: The quantification of transvalvular blood flow through the mitral valve (MV) and regurgitant flow in particular is difficult with echocardiography, which is the method of choice to diagnose patients selected for valve repair or replacement. With magnetic resonance imaging, information on the intraventricular blood flow can be obtained. Several scanning techniques have attempted to assess the regurgitant flow. These techniques either do not directly assess the complete flow through the MV, or they do not measure the flow at the location of the valve. AIM: To investigate the accuracy of a novel method using three-directional velocity-encoded MRI to acquire the transvalvular blood flow directly from the intraventricular blood flow field, also representing the regurgitant flow during systole. METHODS: Ten volunteers without cardiac valvular disease were recruited. The transvalvular MV flow volume was measured with three-directional velocity-encoded MRI (3-dir MV flow). RESULTS: The transvalvular flow measurements correlate very well with the flow measured in the aorta (rp=0.92, p<0.01). The small differences (mean -5±7 ml) are insignificant (p=0.06) and demonstrate the high accuracy of the new method. Intra- and inter-observer studies showed non-significant mean differences of 0.9±5.1 ml and 1.3±5.6 ml, respectively, thereby proving the high reproducibility. CONCLUSION: Three-directional velocity-encoded MRI is a patient-friendly and easy-to-use method suitable for quantifying the regurgitant MV flow in clinical practice.

Three-dimensional navigator coronary MRA with the aid of a blood pool agent in pigs: improved image quality with inclusion of the contrast agent first-pass.

PURPOSE: To evaluate the effect of including the first-pass of a blood pool agent (BPA) on the image quality of three-dimensional navigator coronary MRA. MATERIALS AND METHODS: A pig model was used to perform: 1) T1 simulation of the BPA, based on actual blood samples, and 2) BPA-enhanced three-dimensional navigator coronary MRA, with or without inclusion of the first-pass of the BPA. The acquisitions with inclusion of the first-pass were timed with the use of a test bolus. The acquisitions without first-pass were started one minute after bolus injection (steady-state). A gradient echo acquisition technique with centric k-space sampling was applied. Comparison of both acquisitions was based on determination of contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and vessel length. RESULTS: T1 simulation shows a distinct T1 reduction during first-pass (to a level below 50 msec), increasing to 190 msec during steady-state. Images obtained with first-pass inclusion showed improved CNR (8.6 +/- 1.7 vs. 4.5 +/- 1.8), SNR (11.9 +/- 1.6 vs. 7.4 +/- 2.0), and vessel length (99.2 +/- 10.9 mm vs. 60.5 +/- 21.8 mm) as compared to the acquisitions during steady-state only (all: P< 0.05). CONCLUSION: The image quality of three-dimensional navigator coronary MRA combined with a gadolinium BPA in pigs is improved when starting the image acquisition during first-pass of the bolus.

A neuroimaging follow up study of a patient with juvenile central nervous system systemic lupus erythematosus.

BACKGROUND: The course of central nervous system systemic lupus erythematosus (CNS-SLE) is largely unknown. New imaging techniques are available to assist in monitoring the disease course. OBJECTIVE: To report a case of juvenile CNS-SLE, in which magnetic resonance imaging (MRI) was used to assess disease activity. CASE REPORT: A 10-year-old female patient with SLE presented with convulsions; MRI and computed tomography (CT) of the cerebrum disclosed abnormalities. Despite adequate treatment, two years later she had a generalised convulsion, and MRI showed new lesions. MR spectroscopy (MRS) indicated neuronal loss, inflammation, and metabolically compromised tissue; magnetisation transfer imaging (MTI) showed an increase in whole brain lesion load. After exclusion of a malignancy, CNS-SLE was the most likely diagnosis, and cyclophosphamide pulses were administered. Initially, multiple sclerosis (MS)-like lesions regressed, but despite maximal immunosuppressive drugs, new lesions formed and disappeared. When immunosuppressive drugs had been stopped for six months MRI showed improved lesions and MTI histograms. DISCUSSION: In this case report, the anatomical substrate, metabolic aspect, neuroimaging, and clinical course of MS-like lesions in a child with CNS-SLE are described. The way in which radiological techniques can support clinical decision making in this young patient with progressive CNS-SLE is illustrated.

Magnetic resonance imaging of ischemic heart disease: why cardiac magnetic resonance imaging will play a significant role in the management of patients with coronary artery disease.

The role of magnetic resonance imaging in the diagnosis of ischemic heart disease has great potential impact on patient management, because a number of aspects of ischemic heart disease can be evaluated in one imaging session. High resolution coronary magnetic resonance angiography is currently available, although several technical improvements are awaited to make the technique routinely applicable. A major advance will probably include the availability of magnetic resonance blood pool contrast agents to improve vessel visualization. Contrast media, in combination with either first pass or delayed myocardial scanning, will also play an important role in myocardial perfusion imaging. Functional magnetic resonance assessment of regional and global ventricular function is currently a well-established technique and is considered a new gold standard, which may impact on routine cardiology practice. This review summarizes some of the recent magnetic resonance developments for evaluating various aspects of ischemic heart disease, including magnetic resonance coronary angiography, flow imaging, and imaging of myocardial perfusion and function.

Diagnosis and management of anomalous origin of the right coronary artery from the left coronary sinus.

The anomalous origin of the right coronary artery (RCA) from the left sinus of Valsalva coursing between the aorta and the pulmonary artery or right ventricular outflow tract, is considered a potentially fatal abnormality which may require surgery. However, diagnosing the correct course with coronary arteriography may be difficult. Fast gradient echo magnetic resonance (MR) imaging can be helpful to identify and confirm the course of aberrant coronary arteries and their relationship to the surrounding tissue. In this study, diagnostic procedures and management are described of four patients in whom the RCA originated from the left sinus of Valsalva. Although reported as investigational by the Task Force document on MR imaging by the European Society of Cardiology we are of the opinion that MR coronary angiography may have an important future role in the assessment of anomalous coronary arteries.

Blood pool contrast agent CMD-A2-Gd-DOTA-enhanced MR imaging of infarcted myocardium in pigs.

The purpose of this study was to assess the ability of the new blood pool contrast agent meglumine-carboxymethyldextran-ethylenediamino-gadoterate (CMD-A2-Gd-DOTA) to depict acute occlusive myocardial infarction (AMI). First-pass gradient-echo and delayed spin-echo magnetic resonance imaging (MRI) was performed 5 days after induction of AMI in a pig model. MRI was correlated with pathology. First-pass imaging with CMD-A2-Gd-DOTA allowed detection of infarcted myocardium in all pigs (n = 7). The infarction was recognized as a black spot on MRI as well as on a parametric image. The signal intensity (SI) amplitudes of normal versus infarcted myocardium were 80.55 +/- 18.61 versus 8.48 +/- 15.50 on MRI and 81.62 +/- 18.50 versus 1.61 +/- 3.73 on the parametric image (both P values < 0.001. The contrast ratio between normal and infarcted myocardium was not significantly improved on spin-echo MRI, suggesting largely intact vascular integrity outside the occluded area. CMD-A2-Gd-DOTA is useful for depicting occlusive myocardial infarction by first-pass MRI. Spin-echo imaging is promising in assessing vascular integrity. J. Magn. Reson. Imaging 1999;10:170-177.

Infarcted myocardium in pigs: MR imaging enhanced with slow-interstitial-diffusion gadolinium compound P760.

PURPOSE: To assess the value of P760, a gadolinium chelate with slow interstitial diffusion and high relaxivity, for magnetic resonance (MR) imaging of acute myocardial infarction in pigs. MATERIALS AND METHODS: First-pass gradient-echo MR imaging and spin-echo MR imaging were performed with P760 and then with gadoterate meglumine in eight pigs with occlusive acute myocardial infarction. P760 signal intensity enhancement and clearance were compared with those of gadoterate meglumine. RESULTS: The first-pass enhancement ratio of P760 in normal myocardium was higher than that in infarcted myocardium (1.37 +/- 0.06 [SEM] vs 1.05 +/- 0.03, P = .03). The myocardial first pass showed a blood pool-like curve for P760. The blood pool enhancement ratio 40 seconds after injection was higher for P760 than for gadoterate meglumine (left ventricular cavity, 1.75 +/- 0.06 vs 1.45 +/- 0.06, P = .009). Spin-echo MR imaging showed improved contrast between normal and infarcted myocardium after P760 administration: The ratio before contrast material administration was 0.21 +/- 0.03, that at 15 minutes was 0.48 +/- 0.05 (P = .002), and that at 25 minutes was 0.47 +/- 0.07 (P = .003). CONCLUSION: P760 is an MR imaging contrast agent characterized by low diffusion, a blood pool effect soon after low-dose administration, and fast elimination. This agent is useful for improved myocardial perfusion MR imaging of acute myocardial infarction.

Equilibrium phase MR angiography of the aortic arch and abdominal vasculature with the blood pool contrast agent CMD-A2-Gd-DOTA in pigs.

Meglumine-carboxymethyldextran-ethylenediamino-gadoterate (CMD-A2-Gd-DOTA) was evaluated as a blood pool contrast agent for magnetic resonance angiography (MRA). MRA of large body vasculature was performed in seven pigs using a gradient-echo sequence at 1.5 T before and after 0.05 mmol/kg CMD-A2-Gd-DOTA injection. The signal- and contrast-to-noise ratios (SNRs, CNRs) were measured, as well as the pharmacokinetic clearance pattern. CMD-A2-Gd-DOTA visualized the vasculature with a high SNR and CNR for over 110 minutes after injection, but for the renal arteries the CNR was only significant within 15 minutes. Image quality was maximum within 15 minutes, producing enhancement (mean +/- SD) as follows: aortic arch 738 +/- 272%, abdominal aorta 393 +/- 123%, left renal artery 202 +/- 95%, right renal artery 248 +/- 107%, inferior vena cava 371 +/- 129%, and portal vein 513 +/- 145%, all P values < or =0.001. The clearance pattern was triphasic. Due to the excellent enhancement of vasculature without background enhancement, CMD-A2-Gd-DOTA is potentially a useful MR blood pool contrast agent for equilibrium phase MRA.

Correlation of heart rate variability with cardiac functional and metabolic variables in cyclists with training induced left ventricular hypertrophy.

OBJECTIVE: To examine the correlation between heart rate variability and left ventricular mass in cyclists with an athlete's heart. METHODS: Left ventricular mass and diastolic function were determined at rest and myocardial high energy phosphates were quantified at rest and during atropine-dobutamine stress in 12 male cyclists and 10 control subjects, using magnetic resonance techniques. Ambulatory 24 hour ECG recordings were obtained, and time and frequency domain heart rate variability indices were computed. RESULTS: In the cyclists, the mean of all RR intervals between normal beats (meanNN), the SD of the RR intervals, and their coefficient of variation were significantly greater than in control subjects (p < 0.01, p < 0.01, and p < 0.05, respectively). For cyclists and control subjects, only meanNN correlated with left ventricular mass (r = 0.48, p = 0.038). The heart rate variability indices that correlated with functional or metabolic variables were: meanNN v E/A peak (the ratio of peak early and peak atrial filling rate) (r = 0.48, p = 0.039); the root mean square of successive differences in RR intervals among successive normal beats v E/A area (ratio of peak early and peak atrial filling volume) (r = 0.48, p = 0.040); percentage of successive RR intervals differing by more than 50 ms v the phosphocreatine to ATP ratio at rest (r = 0.54, p = 0. 017); and the SD of the average RR intervals during all five minute periods v the phosphocreatine to ATP ratio during stress (r = 0.60, p = 0.007). CONCLUSIONS: Highly trained cyclists have increased heart rate variability indices, reflecting increased cardiac vagal control compared with control subjects. Left ventricular mass has no major influence on heart rate variability, but heart rate variability is significantly correlated with high energy phosphate metabolism and diastolic function.

Diastolic dysfunction in hypertensive heart disease is associated with altered myocardial metabolism.

BACKGROUND: Hypertension is an important clinical problem and is often accompanied by left ventricular (LV) hypertrophy and dysfunction. Whether the myocardial high-energy phosphate (HEP) metabolism is altered in human hypertensive heart disease and whether this is associated with LV dysfunction is not known. METHODS AND RESULTS: Eleven patients with hypertension and 13 age-matched healthy subjects were studied with magnetic resonance imaging at rest and with phosphorus-31 magnetic resonance spectroscopy at rest and during high-dose atropine-dobutamine stress. Hypertensive patients showed higher LV mass (98+/-28 g/m2) than healthy control subjects (73+/-13 g/m2, P<0.01). LV filling was impaired in patients, reflected by a decreased peak rate of wall thinning (PRWThn), E/A ratio, early peak filling rate, and early deceleration peak (all P<0. 05), whereas systolic function was still normal. The myocardial phosphocreatine (PCr)/ATP ratio determined in patients at rest (1. 20+/-0.18) and during stress (0.95+/-0.25) was lower than corresponding values obtained from healthy control subjects at rest (1.39+/-0.17, P<0.05) and during stress (1.16+/-0.18, P<0.05). The PCr/ATP ratio correlated significantly with PRWThn (r=-0.55, P<0.01), early deceleration peak (r=-0.56, P<0.01), and with the rate-pressure product (r=-0.53, P<0.001). CONCLUSIONS: Myocardial HEP metabolism is altered in patients with hypertensive heart disease. In addition, there is an association between impaired LV diastolic function and altered myocardial HEP metabolism in humans. The level of myocardial PCr/ATP is most likely determined by the level of cardiac work load.

Changes in muscle volume, strength, and bioenergetics during recombinant human growth hormone (GH) therapy in adults with GH deficiency.

Adults with GH deficiency (GHD) suffer from muscle weakness, which can be caused by the frequently reported decrease in muscle mass. However, measurements of both muscle strength and mass of muscle tested are scarce in adults with GHD. The aim of the present study was, therefore, to investigate intrinsic muscle strength (strength expressed per muscle volume unit) in adults with GHD at baseline and after 52 weeks of recombinant human GH (rhGH) therapy given in low, more physiological doses. A second objective was to investigate the influence of GH on muscle bioenergetics in the resting muscle. Isometric and isokinetic quadriceps strengths were measured in 28 males with GHD and in healthy controls matched for age and height. Quadriceps mass, determined by magnetic resonance imaging, and muscle bioenergetics, determined by phosphorus nuclear magnetic resonance spectroscopy, were measured in 20 of 28 patients with GHD and in controls matched for age and height. All patients were treated with doses of rhGH ranging from 0.6-1.8 IU/day, given for 52 weeks. Measurements of muscle mass, strength, and bioenergetics were repeated after 52 weeks of treatment with rhGH. The mean GH dose at 52 weeks of rhGH treatment was 1.3 +/- 0.8 IU/day. The mean serum insulin-like growth factor I level at baseline was 9.4 +/- 0.7 nmol/L and significantly increased to 26.4 +/- 1.2 nmol/L after 52 weeks of rhGH treatment. Adults with GHD had significantly reduced quadriceps muscle mass (P = 0.034) and reduced isometric muscle strength (P = 0.002) and tended to have low isokinetic muscle strength (P = 0.06), which all improved after rhGH therapy. Intrinsic muscle strength was not significantly different in adults with GHD compared with that in healthy controls and did not change during rhGH therapy. No bioenergetic abnormalities at baseline or after rhGH therapy were found in males with GHD. In conclusion, quadriceps muscle mass is decreased in adults with GHD and increased with rhGH therapy. These changes in muscle mass account for the changes in muscle strength found in these patients, as no changes in intrinsic muscle strength were found.