Modeling-based bone formation transforms trabeculae to cortical bone in the sclerotic areas in Buschke-Ollendorff syndrome. A case study of two females with LEMD3 variants.

Buschke-Ollendorff syndrome is a rare autosomal dominant condition caused by pathogenic variants in LEMD3 and characterized by connective tissue nevi and sclerotic bone abnormalities known as osteopoikilosis. The bone phenotype in Buschke-Ollendorff syndrome including osteopoikilosis remains unclear. We investigated bone turnover markers, pelvis and crura X-rays; lumbar spine and femoral neck DXA; bone activity by NaF-PET/CT, bone structure by µCT and dynamic histomorphometry in adults with Buschke-Ollendorff syndrome. Two women aged 25 and 47 years with a BMI of 30 and 32 kg/m2, respectively, were included in the investigation. Bone turnover markers were within normal range. aBMD Z-scores were comparable to that of controls in the lumbar spine and increased at the hip. Radiographies exposed spotted areas in crura and pelvis, and NaF-PET/CT exposed abnormal pattern of irregular shaped NaF uptake in the entire skeleton. In both biopsies, µCT showed trabecular structure comparable to that of controls with stellate shaped sclerotic noduli within the cavity and on the endocortex. Histomorphometric analyses of the sclerotic lesions revealed compact lamellar bone with a normal bone remodeling rate, but partly replaced by modeling-based bone formation. Woven bone was not observed in the nodules. Therefore, while bone turnover and BMD were largely within normal reference range in patients with the Buschke-Ollendorff syndrome, osteosclerotic lesions appear to emerge due to modeling-based bone formation with secondary bone remodeling. These observations indicate that LEMD3 may be important for the activation of bone lining cells leading to modeling-based bone formation.

Maternal SSRI exposure increases the risk of autistic offspring: A meta-analysis and systematic review.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the most common antidepressants used to preclude maternal pregnancy depression. There is a growing body of literature assessing the association of prenatal exposure to SSRIs with autism spectrum disorder (ASD). The present systematic review and meta-analysis reviewed the medical literature and pooled the results of the association of prenatal exposure to SSRIs with ASD. METHODS: Published investigations in English by June 2016 with keywords of selective serotonin reuptake inhibitors, SSRI, autism spectrum disorder, ASD, pregnancy, childhood, children, neurodevelopment were identified using databases PubMed and PMC, MEDLINE, EMBASE, SCOPUS, and Google Scholar. Cochran's Q statistic-value (Q), degree of freedom (df), and I2 indices (variation in odds ratio [OR] attributable to heterogeneity) were calculated to analyze the risk of heterogeneity of the within- and between-study variability. Pooled odds ratio (OR) and 95% confidence interval (CI) were reported by a Mantel-Haenszel test. RESULTS: There was a non-significant heterogeneity for the included studies ([Q=3.61, df=6, P=0.730], I2=0%). The pooled results showed a significant association between prenatal SSRI exposure and ASD (OR=1.82, 95% CI=1.59-2.10, Z=8.49, P=0.00). CONCLUSION: The evidence from the present study suggests that prenatal exposure to SSRIs is associated with a higher risk of ASD.

Strategies for CT tissue segmentation for Monte Carlo calculations in nuclear medicine dosimetry.

PURPOSE: CT images are used for patient specific Monte Carlo treatment planning in radionuclide therapy. The authors investigated the impact of tissue classification, CT image segmentation, and CT errors on Monte Carlo calculated absorbed dose estimates in nuclear medicine. METHODS: CT errors as a function of patient size, CT reconstruction, and tube current modulation methods were assessed in a phantom experiment on a clinical CT system. The impact of tissue segmentation methods and CT number variations on EGSnrc Monte Carlo calculated absorbed dose distributions was assessed for 99mTc and 131I in the ICRP/ICRU male phantom and in a patient PET/CT-scanned with 124I prior to radioiodine therapy. RESULTS: CT number variations <20 HU were obtained for whole-body CT examinations at effective CT doses ∼2 mSv. Monte Carlo calculated absorbed doses depended on both the number of media types and accurate calibration of the CT number-to-density conversion ramp. Tissue segmentation by a 13-tissue CT conversion ramp, calibrated by a stoichiometric method, resulted in low (<4%) dose errors in selected organs for both isotopes. CONCLUSIONS: A calibrated CT scanner specific conversion ramp is required for accurate patient specific dosimetry in nuclear medicine. Accurate dosimetry was obtained with a 13-tissue ramp that included five different bone types.

Detection of bone metastases in breast cancer patients in the PET/CT era: Do we still need the bone scan?

AIM: To examine the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for the detection of bone metastasis in breast cancer patients and assess whether whole body bone scan (BS) with (99m)Tc-methylene diphosphonate provides any additional information. MATERIAL AND METHODS: Study group comprised 150 patients, mean age 52 years (range 27-85) with breast cancer, suspected of having bone metastases. All patients had undergone both FDG-PET/CT and BS with or without single photon emission tomography/computed tomography (SPECT/CT) within a period of 6 weeks. The final diagnosis of bone metastasis was established by histopathological findings, additional imaging, or clinical follow-up longer than 10 months. Cancer antigen 15-3 (CA15-3) and carcinoembryogenic antigen (CEA) were measured in all patients. RESULTS: Histologically 83%, 7% and 10% had infiltrating ductal, lobular and mixed carcinoma respectively. Confirmed bone metastases were present in 86 patients (57.3%) and absent in 64 (42.7%). Mean CA15-3 and CEA values in patients with bone metastases were 74.6ng/mL and 60.4U/mL respectively, compared to 21.3ng/mL and 3.2U/mL without metastases (p<0.001). The sensitivity of FDG-PET/CT for the detection of bone metastases was 97.6% compared to 89.5% with SPECT/CT. In 57 patients, FDG-PET/CT correctly identified additional pulmonary, hepatic, nodal and other soft tissue metastases, not detected by BS. CONCLUSION: Our findings suggest that FDG-PET/CT is superior to BS with or without SPECT/CT.

Impact of high (131)I-activities on quantitative (124)I-PET.

Peri-therapeutic (124)I-PET/CT is of interest as guidance for radioiodine therapy. Unfortunately, image quality is complicated by dead time effects and increased random coincidence rates from high (131)I-activities. A series of phantom experiments with clinically relevant (124)I/(131)I-activities were performed on a clinical PET/CT-system. Noise equivalent count rate (NECR) curves and quantitation accuracy were determined from repeated scans performed over several weeks on a decaying NEMA NU-2 1994 cylinder phantom initially filled with 25 MBq (124)I and 1250 MBq (131)I. Six spherical inserts with diameters 10-37 mm were filled with (124)I (0.45 MBq ml(-1)) and (131)I (22 MBq ml(-1)) and placed inside the background of the NEMA/IEC torso phantom. Contrast recovery, background variability and the accuracy of scatter and attenuation corrections were assessed at sphere-to-background activity ratios of 20, 10 and 5. Results were compared to pure (124)I-acquisitions. The quality of (124)I-PET images in the presence of high (131)I-activities was good and image quantification unaffected except at very high count rates. Quantitation accuracy and contrast recovery were uninfluenced at (131)I-activities below 1000 MBq, whereas image noise was slightly increased. The NECR peaked at 550 MBq of (131)I, where it was 2.8 times lower than without (131)I in the phantom. Quantitative peri-therapeutic (124)I-PET is feasible.

PET imaging with the non-pure positron emitters: (55)Co, (86)Y and (124)I.

PET/CT with non-pure positron emitters is a highly valuable tool in immuno-PET and for pretherapeutic dosimetry. However, imaging is complicated by prompt gamma coincidences (PGCs) that add an undesired background activity to the images. Time-of-flight (TOF) reconstruction improves lesion detectability in (18)F-PET and can potentially also improve the signal-to-noise ratio in images acquired with non-pure positron emitters. Using the GE Discovery 690 PET/CT system, we evaluated the image quality with (55)Co, (86)Y and (124)I, and the effect of PGC-correction and TOF-reconstruction on image quality and quantitation in a series of phantom studies. PET image quality and quantitation for all isotopes were significantly affected by PGCs. The effect was most severe with (86)Y, and less, but comparable, with (55)Co and (124)I. PGC-correction improved the image quality and the quantitation accuracy dramatically for all isotopes, especially when the activity was limited to a few hot lesions in a warm background. In imaging situations, where high levels of activity were present in the background, activity concentrations were overestimated. TOF-reconstruction improved image quality in isolated lesions but worsened the accuracy of quantitation and uniformity in homogeneous activity distributions. Better modelling of PGCs in the scatter correction can potentially improve the situation.

Renal cortical and medullary blood flow during modest saline loading in humans.

AIM: Renal medullary blood flow (RMBF) is considered an important element of sodium homeostasis, but the experimental evidence is incongruent. Studies in anaesthetized animals generally support the concept in contrast to measurements in conscious animals. We hypothesized that saline-induced natriuresis is associated with changes in RMBF in humans. METHODS: After 4 days of low-sodium diet, healthy men were subjected to slow intravenous saline loading (12 µmol kg(-1) min(-1)) for 4 h. Renal medullary and cortical blood flow was determined by positron emission tomography with H(2)(15)O before and after saline infusion using two independent imaging processing methods. One based on a previously published algorithm (voxel peeling) and a novel method based on contrast-enhanced computed tomography (CT). Blood pressure was measured oscillometrically every 10 min. Cardiac output, heart rate and total peripheral resistance were recorded continuously. RESULTS: Saline loading increased the urinary sodium excretion by 3.6-fold (21-76 µmol min(-1) , P < 0.01). The RMBF was 2.6 ± 0.2 mL g(-1) tissue min(-1) before and 2.7 ± 0.1 mL g(-1) tissue min(-1) after saline (n.s.). Cortical blood flow was 3.6 ± 0.1 before and 3.4 ± 0.2 after saline (n.s.). Mean arterial blood pressure did not change measurably (90 vs. 90 mmHg). Bland-Altman analysis suggested agreement between results obtained with voxel peeling (2.6 ± 0.2 mL g(-1) tissue min(-1)) and contrast-enhanced CT (2.0 ± 0.1 mL g(-1) tissue min(-1)). CONCLUSION: In normal humans, changes in RMBF are not necessarily involved in the natriuretic response to modest saline loading. This result is in line with data from conscious rodents.

Identification of asymptomatic type 2 diabetes mellitus patients with a low, intermediate and high risk of ischaemic heart disease: is there an algorithm?

AIMS/HYPOTHESIS: The leading cause of death in type 2 diabetes is cardiovascular disease (CVD). We examined the prevalence of myocardial ischaemia in type 2 diabetes patients and tried to establish an algorithm to identify patients with a high risk of ischaemic heart disease. METHODS: Type 2 diabetes patients who had no known or suspected CVD, and had been referred consecutively to a diabetes clinic for the first time (n=305; age 58.6+/-11.3 years; diabetes duration 4.5+/-5.3 years) were screened for myocardial ischaemia using myocardial perfusion scintigraphy (MPS). RESULTS: The univariate predictors of myocardial ischaemia were: atypical or typical angina pectoris, two or more traditional risk factors for CVD, BMI >32 kg/m2, systolic blood pressure >140 mmHg, HbA1c >8.5%, high-sensitivity C-reactive protein >4.0 mg/l, N-terminal pro-brain natriuretic peptide >300 pg/ml, left atrial volume index >32 ml/m2, left ventricular ejection fraction <50%, and carotid and peripheral arterial disease. The algorithm identified low (n=96), intermediate (n=65) and high risk groups (n=115), in which the prevalence of myocardial ischaemia was 15%,23% and 43%, respectively. Overall the algorithm reduced the number of patients referred to MPS from 305 to 144.However, the sensitivity and specificity of the algorithm was just 68% and 62%, respectively. CONCLUSIONS/INTERPRETATION: Our algorithm was able to stratify which patients had a low, intermediate or high risk of myocardial ischaemia based on MPS. However, the algorithm had low sensitivity and specificity, combined with high cost and time requirements. TRIAL REGISTRATION: clinicaltrials.gov NCT00298844 FUNDING: The study was funded by the Danish Cardio vascular Research Academy (DaCRA), The Danish Diabetes Association and The Danish Heart Foundation.

Systemic nitric oxide clamping in normal humans guided by total peripheral resistance.

AIM: We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels. METHODS: Normal volunteers (23-28 years) were infused i.v. with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) at 0.5 mg kg(-1) h(-1). One hour later, the NO donor sodium nitroprusside (SNP) was co-infused in doses eliminating the haemodynamic effects of l-NAME. Haemodynamic measurements included blood pressure (MABP) and cardiac output (CO) by impedance cardiography. RESULTS: l-NAME increased MABP and total peripheral resistance (TPR, 1.02 + or - 0.05 to 1.36 + or - 0.07 mmHg s mL(-1), mean + or - SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 + or - 0.05 mmHg s mL(-1), P < 0.05). CO decreased with l-NAME (5.8 + or - 0.3 to 4.7 + or - 0.3 L min(-1), P < 0.01) and returned to control when SNP was added (6.0 + or - 0.3 L min(-1)). A decrease in plasma noradrenaline (42%, P < 0.01) during l-NAME administration was completely reversed by SNP. Plasma renin activity decreased during l-NAME administration and returned towards normal after addition of SNP. In contrast, plasma aldosterone was increased by l-NAME and remained elevated. CONCLUSIONS: Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation.

PET/CT in cancer: Methodological considerations for comparative diagnostic phase II studies with paired binary data.

OBJECTIVES: When the combined diagnostic imaging technique PET/CT is considered promising with respect to diagnosis/staging of a certain cancer type, a systematic investigation by means of clinical diagnostic studies in the target population is necessary to evaluate the usefulness of PET/CT compared to the current standard. It is often difficult to decide in advance whether it is appropriate to plan a superiority or non-inferiority study. We propose a statistical analysis strategy which is flexible enough to cope with both aims alike. METHODS: In opposition to clinical studies on drugs, each patient can be subjected to both PET/CT and the current standard, leading to paired observations of binary data (e.g., cancer = yes/no, stage = 0/1+). The analysis strategy focuses on point estimates and confidence intervals for the difference (or relative increase) in accuracy measures. RESULTS: Formulas for approximate 95% confidence intervals for the differences in sensitivity, specificity, positive and negative predictive values between PET/CT and the standard procedures are given, respectively. The strategy can also be applied if results obtained with a golden standard are not available in patients in whom both PET/CT and the standard procedure gave negative results. Sample sizes can and should be determined in an adaptive manner. CONCLUSIONS: Diagnostic studies to assess the merit of PET/CT in the diagnostic work-up of cancer patients can and should start with phase II studies focusing on 95% confidence intervals for differences in diagnostic measures. Even if the gold standard procedure is incomplete, the statistical analysis strategy given here may still be applicable.

External dose rates in radioiodine treatment of benign goitre: estimation versus direct measurement.

OBJECTIVE: According to European recommendations, the external dose rate (ED) in radioiodine-treated goitre patients can be determined by estimating from calculation of the residual activity (RA) in the patient based on radioiodine uptake measurements or by measuring ED directly. In the European guidelines, "Radiation Protection 97", it is assumed that an RA of 600 MBq (131)I causes an ED of 30 microSv/h at a distance of 1 m. This implies a slope of 0.05 microSv/h/MBq for the ratio ED/RA relationship, but, theoretically, this ratio is higher, at 0.07, a difference that is due to measurement in air versus in a scattering medium. We sought to investigate what the true ratio might be. MATERIAL AND METHODS: Sixty-six patients scheduled for radioiodine treatment of benign goitre (mean size 102 mL, range 20-440), who received (131)I orally (mean 984 MBq, range 173-3700) were examined. After 24 h and 96 h iodine uptake percentage we examined 7269 patients scheduled for radioiodine treatment of benign goitre (mean size 1042 mL, range 20-440) who received (131)I orally (mean 101,100 MBq, range 180-3700). After 24 h and 96 h, the iodine uptake was determined, RA calculated and ED measured using a hand-held dosimeter. RESULTS: At 24 and 96 h, we observed a slope ratio of 0.103 microSv/h/MBq (95 % CI: 0.09564-0.111) and 0.101 microSv/h/MBq (95 % CI: 0.0915-0.11107), respectively, for the ED/RA relationship. None of the confidence intervals included the value 0.05 microSv/h/MBq, reflecting that the observed slopes differed significantly from the expected slope (p < 0.001). Consequently, an RA of 600 MBq typically causes an ED of 60 and not 30 microSv/h, and therefore dose rates based on radioiodine uptake measurements and established assumptions were only about half as high as the directly measured values. We noticed that with an RA roughly below 450 MBq, the anticipated slope of 0.05 microSv/h/MBq is within the prediction interval of our claimed ratio, therefore we cannot rebut the anticipated slope for lower doses. CONCLUSIONS: Dose-rate estimates based on radioiodine uptake measurements and established assumptions were only about half as high as the directly measured values in patients receiving doses higher than the widely accepted limits for outpatient treatment. This finding may have substantial implications for us, in that it makes a considerable difference whether the radiation precautions are taken to limit doses to the patient's surroundings and for deciding if a patient may or may not be regarded as an outpatient, as well as for the safe discharge of an inpatient from hospital.

Effects of oxytocin in normal man during low and high sodium diets.

AIM: We tested the hypothesis that oxytocin in normal man causes natriuresis by means of nitric oxide and/or atrial natriuretic peptide. METHODS: Normal male subjects were investigated after 4 days of sodium controlled diets (30 mmol sodium chloride day(-1), n = 8 or 230 mmol sodium chloride day(-1), n = 6). Oxytocin was infused intravenously (1 pmol kg(-1) min(-1) for 240 min). RESULTS: Mean arterial blood pressure, heart rate and glomerular filtration rate by clearance of chromium-labelled ethylenediaminetetraacetate remained stable. Plasma oxytocin increased from 2 to 3 pg mL(-1) to around 50 pg mL(-1). Oxytocin decreased urine flow (4.2 +/- 0.2--0.75 +/- 0.11 and 4.6 +/- 1.3-1.4 +/- 0.6 mL min(-1), low- and high-salt diet, respectively). During low-salt conditions, oxytocin reduced sodium and potassium excretion (11 +/- 2--4 +/- 2 and 93 +/- 19--42 +/- 3 micromol min(-1), respectively). Plasma renin, angiotensin II, aldosterone and renal excretion of metabolites of nitric oxide (nitrate and nitrite) all decreased. Plasma atrial natriuretic peptide and cyclic guanosine monophosphate were unchanged. A similar pattern was obtained during high-salt conditions but in this case the antinatriuresis was not different from that occurring during the corresponding time control series. CONCLUSIONS: The data reject the hypothesis. In contrast, we found significant antinatriuretic, antikaliuretic and antidiuretic effects, which were not mediated by the renin-angiotensin-aldosterone system, atrial natriuretic peptide, systemic haemodynamics, or processes increasing urinary excretion of metabolites of nitric oxide. The natriuretic effect of oxytocin found in laboratory animals is species-specific.

Mechanisms of acute natriuresis in normal humans on low sodium diet.

This study evaluates the relative importance of several mechanisms possibly involved in the natriuresis elicited by slow sodium loading, i.e. the renin-angiotensin-aldosterone system (RAAS), mean arterial blood pressure (MAP), glomerular filtration rate (GFR), atrial natriuretic peptide (ANP), oxytocin and nitric oxide (NO). Eight seated subjects on standardised sodium intake (30 mmol NaCl day(-1)) received isotonic saline intravenously (NaLoading: 20 micromol Na(+) kg(-1) min(-1) or approximately 11 ml min(-1) for 240 min). NaLoading did not change MAP or GFR (by clearance of (51)Cr-EDTA). Significant natriuresis occurred within 1 h (from 9 +/- 3 to 13 +/- 2 micromol min(-1)). A 6-fold increase was found during the last hour of infusion as plasma renin activity, angiotensin II (ANGII) and aldosterone decreased markedly. Sodium excretion continued to increase after NaLoading. During NaLoading, plasma renin activity and ANGII were linearly related (R = 0.997) as were ANGII and aldosterone (R = 0.999). The slopes were 0.40 pM ANGII (mi.u. renin activity)(-1) and 22 pM aldosterone (pM ANGII)(-1). Plasma ANP and oxytocin remained unchanged, as did the urinary excretion rates of cGMP and NO metabolites (NO(x)). In conclusion, sodium excretion may increase 7-fold without changes in MAP, GFR, plasma ANP, plasma oxytocin, and cGMP- and NO(x) excretion, but concomitant with marked decreases in circulating RAAS components. The immediate renal response to sodium excess appears to be fading of ANGII-mediated tubular sodium reabsorption. Subsequently the decrease in aldosterone may become important.

Myocardial perfusion imaging and coronary angiography in patients with known or suspected stable angina pectoris.

INTRODUCTION: The patho-physiological cause of angina pectoris is myocardial ischaemia, which can be objectified by myocardial perfusion imaging (MPI). METHODOLOGY: MPI was undertaken prior to coronary angiography (CAG) in 86 randomly selected patients with known or suspected stable angina pectoris. RESULTS: Among 78 adequately stressed patients, MPI was normal in 28 (36%) and showed reversible and irreversible perfusion abnormalities in 30 (38%) and 20 patients (26%), respectively. Coronary angiograms were normal in 28 (36%) and revealed at least one > or = 50% stenosis in 50 patients (64%) (16 with single and 34 with multi vessel disease). Using angiography as a reference, the sensitivity and specificity of MPI in detecting coronary artery disease was 88% and 93%, respectively. DISCUSSION: MPI demonstrates regional hypoperfusion whereas CAG depicts anatomical stenosis in epicardial arteries. Both modalities are potentially relevant in patients with stable angina pectoris. The functional significance of coronary artery lesions is, however, variable and MPI can demonstrate normal myocardial perfusion in the presence of moderate lesions. MPI exhibited a high sensitivity and specificity regarding significant lesions. More than one third of the subjects had a normal MPI and a normal CAG. Patients with stable angina pectoris and a normal MPI have a very low risk of cardiac events and do usually not require further invasive investigation or therapy. Reversible ischaemia and irreversible ischaemia with demonstration of viable tissue call for coronary revascularisation.

Interpretive intra- and interobserver reproducibility of rest/stress 99Tcm-sestamibi myocardial perfusion SPECT in a consecutive group of male patients with stable angina pectoris before and after percutaneous transluminal angioplasty.

BACKGROUND: Observer variability of 99Tcm-sestamibi myocardial perfusion imaging (MPI) has rarely been investigated. The aim of our study was to evaluate the interpretive reproducibility with this technique. PATIENTS: We report on 108 consecutive male patients with stable angina pectoris, investigated before and after percutaneous transluminal angioplasty (PTCA). METHODS: A 2-day rest/stress 99Tcm-sestamibi gated single photon emission computed tomography (SPECT) protocol was used. MPI was interpreted by two independent observers without knowledge of clinical data, using a 20-segment scoring model. RESULTS: Intra- and interobserver agreement was found to be good to excellent (kappa = 0.71-0.85) with regard to the overall diagnosis as well as the individual vessel diagnosis (kappa = 0.60-0.87). However, agreement was higher for left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX) vascular territories than for the right coronary artery (RCA) territory. Moderate to good intraobserver agreement (kappa = 00.54-0.68) and slightly lower interobserver agreement (kappa = 0.52-0.56) was found for segmental score interpretation. When comparing the interpretive reproducibility before and after PTCA intra- and interobserver agreement was better after PTCA, probably reflecting the increase in normal scans after revascularization. CONCLUSIONS: In a group of consecutive male patients with stable angina pectoris interpretive reproducibility (overall and individual vessel diagnosis) was good to excellent. However, segmental scoring reproducibility was moderate to good.

[Myocardial scintigraphy and coronary arteriography in patients with known or suspected stable angina pectoris]. / Myokardiescintigrafi og koronararteriografi hos patienter med kendt eller formodet stabil angina pectoris.

INTRODUCTION: Myocardial perfusion imaging (MPI) demonstrates regional hypoperfusion, whereas coronary angiography shows anatomical stenoses in epicardial arteries. Both modalities are potentially relevant in patients with stable angina pectoris. MATERIALS AND METHODS: MPI was undertaken before angiography in 86 randomly selected patients with stable angina pectoris. RESULTS: Of 78 adequately stressed patients, MPI was normal in 28 (36%) and showed reversible and irreversible perfusion abnormalities in 30 (38%) and 20 patients (26%), respectively. Coronary angiograms were normal in 28 (36%) and revealed at least one > or = 50% stenosis in 50 patients (64%) (16 with single vessel and 34 with multivessel disease). With angiography as reference, the sensitivity and specificity of MPI in the detection of coronary artery disease were 88% and 93%, respectively. DISCUSSION: Patients with stable angina pectoris and a normal MPI have a very low risk of cardiac events and do not usually require invasive investigation and therapy. Reversible ischaemia and irreversible ischaemia with viable tissue call for coronary revascularisation.

In vivo secretory potential and the effect of combination therapy with octreotide and cabergoline in patients with clinically non-functioning pituitary adenomas.

The secretory capacity, in vivo, of clinically non-functioning pituitary adenomas may possibly predict tumour volume reduction during intensive medical therapy. Ten patients (mean (range) 53 years (26-73)) with clinically non-functioning macroadenomas, > or = 10 mm were studied. The secretory capacity of the adenomas was examined using basal, NaCl and TRH-stimulated LH, FSH and alpha-subunit levels. The effect on tumour volume of 6 months' therapy with the combination of a somatostatin analogue, octreotide 200 microg x 3/day and a dopamine-D2-agonist, cabergoline 0.5 mg x 1/day was studied. The basal LH, FSH and alpha-subunit levels were determined before and during 6 months' therapy with octreotide and cabergoline, and MR scans were used to evaluate tumour volume before and during this period of therapy. Octopus-perimetry was used to examine the visual fields. A reduction in tumour volume (mean +/- SEM (range); 30% +/- 4% (18-46%)) during 6 months of combination therapy with octreotide and cabergoline was recorded only in patients with in vivo secretory potential. Tumour volume was not reduced in four patients: in three of these patients it remained unchanged while in one patient it was observed to have increased (by 14%). Of the six patients with pretherapy secretory capacity, one displayed a very high basal level of alpha-subunit (74 microg/l) despite unmeasurable levels of LH and TSH, and an FSH-level of 1 IU/l. The other five patients presented paradoxical LH, FSH and/or alpha-subunit responses to TRH. A reduction in basal levels of LH, FSH and/or alpha-subunit was observed in all six patients, and the maximum reduction of at least one of the hormonal levels was 66% +/- 7% (50-98%). The basal levels of LH, FSH and alpha-subunit in the 10 patients were (mean +/- SEM (range)), 3.0 IU/l +/- 1.0 (0.0-7.4), 12.7 IU/l +/- 5.0 (0.0-39.0) and 9.0 IU/l +/- 7.0 (0.2-74.0). During six months of therapy with octreotide and cabergoline, the basal levels of LH, FSH and alpha-subunit were reduced by > or = 50% in seven patients - including the six patients with in vivo secretion prior to therapy. No new visual field defects were detected during therapy and no deterioration of existing visual field defects was recorded. The medical therapy was well tolerated. The in vivo basal and TRH-stimulated secretory capacity of LH, FSH and alpha-subunit predicted tumour reduction following intensive medical therapy in all of our patients with non-functioning pituitary adenomas.