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Adjuvant treatment for post-menopausal women with early breast cancer (BC) includes aromatase inhibitors (AI), known to decrease bone mineral density (BMD). In this study, we investigate whether denosumab is a valid second option for patients unable to receive standard adjuvant i.v. zoledronic acid (ZA). In total, 212 patients have been evaluated after they did not receive ZA. Of those 194 were included. After evaluation by an endocrinologist, all patients were offered ZA as their first choice and 15% accepted (

BACKGROUND: SGLT2 inhibitors are a promising treatment option in patients with heart failure and reduced ejection fraction. We aimed to investigate the effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate (GFR) in patients with heart failure and reduced ejection fraction.METHODS: Empire HF Renal was a prespecified substudy of the investigator-initiated, double-blind, randomised, placebo-controlled Empire HF trial. The study was done at Herlev and Gentofte University Hospital (Herlev, Denmark), with patients recruited from four Danish heart failure outpatient clinics. Patients with New York Heart Association class I-III symptoms, with a left ventricular ejection fraction of 40% or lower, and on guideline-directed heart failure therapy were randomly assigned (1:1) to receive either oral empagliflozin 10 mg or matched placebo once daily for 12 weeks. The allocation sequence was computer-generated. Patients and study investigators were masked to treatment allocation. The coprimary prespecified renal outcomes were the between-group difference in the changes in estimated extracellular volume, estimated plasma volume, and measured GFR from baseline to 12 weeks. All analyses were done in the intention-to-treat population (apart from safety analyses, which were done in patients who received at least one dose of study drug), with no interim analyses done during the trial. The Empire HF trial is registered with ClinicalTrials.gov, NCT03198585, and EudraCT, 2017-001341-27.FINDINGS: Between June 29, 2017, and July 15, 2019, we assessed 391 patients for eligibility, of whom 120 (31%) were randomly assigned to empagliflozin or placebo, including 105 (88%) without diabetes. In intention-to-treat analyses, 60 (100%) patients in the empagliflozin group and 59 (98%) patients in the placebo group were included for estimated extracellular volume and estimated plasma volume, and 59 (98%) patients in the empagliflozin group and 58 (97%) patients in the placebo group were included for measured GFR. Empagliflozin treatment resulted in reductions in estimated extracellular volume (adjusted mean difference -0·12 L, 95% CI -0·18 to -0·05; p=0·00056), estimated plasma volume (-7·3%, -10·3 to -4·3; pINTERPRETATION: In patients with heart failure and reduced ejection fraction, empagliflozin reduced estimated extracellular volume, estimated plasma volume, and measured GFR after 12 weeks. Fluid volume changes might be an important mechanism underlying the beneficial clinical effects of SGLT2 inhibitors.FUNDING: Research Council at Herlev and Gentofte University Hospital, Research and Innovation Foundation of the Department of Cardiology at Herlev and Gentofte University Hospital, Capital Region of Denmark, Danish Heart Foundation, and AP Møller Foundation for the Advancement of Medical Science.

BackgroundDisturbances in presynaptic dopamine activity and levels of GABA (gamma-aminobutyric acid) and glutamate plus glutamine collectively may have a role in the pathophysiology of psychosis, although separately they are poor diagnostic markers. We tested whether these neurotransmitters in combination improve the distinction of antipsychotic-naïve patients with first-episode psychosis from healthy control subjects.MethodsWe included 23 patients (mean age 22.3 years, 9 male) and 20 control subjects (mean age 22.4 years, 8 male). We determined dopamine metabolism in the nucleus accumbens and striatum from 18F-fluorodopa (18F-FDOPA) positron emission tomography. We measured GABA levels in the anterior cingulate cortex (ACC) and glutamate plus glutamine levels in the ACC and left thalamus with 3T proton magnetic resonance spectroscopy. We used binominal logistic regression for unimodal prediction when we modeled neurotransmitters individually and for multimodal prediction when we combined the 3 neurotransmitters. We selected the best combination based on Akaike information criterion.ResultsIndividual neurotransmitters failed to predict group. Three triple neurotransmitter combinations significantly predicted group after Benjamini-Hochberg correction. The best model (Akaike information criterion 48.5) carried 93.5% of the cumulative model weight. It reached a classification accuracy of 83.7% (p = .003) and included dopamine synthesis capacity (Ki4p) in the nucleus accumbens (p = .664), GABA levels in the ACC (p = .019), glutamate plus glutamine levels in the thalamus (p = .678), and the interaction term Ki4p × GABA (p = .016).ConclusionsOur multimodal approach proved superior classification accuracy, implying that the pathophysiology of patients represents a combination of neurotransmitter disturbances rather than aberrations in a single neurotransmitter. Particularly aberrant interrelations between Ki4p in the nucleus accumbens and GABA values in the ACC appeared to contribute diagnostic information.

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Background: Dopamine activity has been associated with the response to antipsychotic treatment. Our study used a four-parameter model to test the association between the striatal decarboxylation rate of 18F-DOPA to 18F-dopamine (k3) and the effect of treatment on psychotic symptoms in antipsychotic-naïve patients with first-episode psychosis. We further explored the effect of treatment with a partial dopamine D2 receptor agonist (aripiprazole) on k3 and dopamine synthesis capacity (DSC) determined by the four-parameter model and by the conventional tissue reference method. Methods: Sixty-two individuals (31 patients and 31 control subjects) underwent 18F-DOPA positron emission tomography at baseline, and 15 patients were re-examined after 6 weeks. Clinical re-examinations were completed after 6 weeks (n = 28) and 6 months (n = 15). Symptoms were evaluated with the Positive and Negative Syndrome Scale. Results: High baseline decarboxylation rates (k3) were associated with more positive symptoms at baseline (p < .001) and with symptom improvement after 6 weeks (p = .006). Subregion analyses showed that baseline k3 for the putamen (p = .003) and nucleus accumbens (p = .013) and DSC values for the nucleus accumbens (p = .003) were associated with psychotic symptoms. The tissue reference method yielded no associations between DSC and symptoms or symptom improvement. Neither method revealed any effects of group or treatment on average magnitudes of k3 or DSC, whereas changes in dopamine synthesis were correlated with higher baseline values, implying a potential effect of treatment. Conclusions: Striatal decarboxylation rate at baseline was associated with psychotic symptoms and treatment response. The strong association between k3 and treatment effect potentially implicate on new treatment strategies.

Background Use of 11C-Choline PET/CT is gaining ground in detecting hyperfunctioning parathyroid glands in primary hyperparathyroidism. The purpose of this study was to evaluate the robustness of 11C-Choline PET/CT by assessing intra- and inter-observer agreement to determine whether the method was reader sensitive and therefore should only be performed at highly specialised sites with a high number of cases. PET/CT images of 40 patients diagnosed with primary hyperparathyroidism were anonymised and evaluated three times by three readers: an expert reader and two non-experts (non-experts were experienced in PET/CT imaging, but not in 11C-Choline PET/CT in the setting of primary hyperparathyroidism). Number of hyperfunctioning parathyroid glands, location relative to the thyroid gland and confidence of each assessment (low, moderate or high) were noted, and intra- and inter-observer agreement calculated using Fleiss’ kappa method. Sensitivities and specificities of the non-experts were calculated using the expert reader as gold standard. Results Intra-observer agreement was ‘good’ to ‘near perfect’ for all readers. Inter-observer agreement was good between non-experts and the expert, with kappa values ≥ 0.74. Sensitivities between non-experts and the expert were high, > 81%, when assessing which side and 75% when assessing thyroid quadrant. All specificities were > 94%. Reader certainties were ‘high’ in > 80% of cases for the expert and > 70% and > 65%, respectively for the two non-experts. Conclusion 11C-Choline PET/CT is not reader sensitive for the localisation of hyperfunctioning parathyroid glands and may therefore be safely implemented at sites that have a moderate number of cases. Access to a cyclotron laboratory is, however, a necessity for the production of 11C-Choline. The study was conducted in accordance with the Helsinki 2 declaration and The International Council for Harmonisation Guideline for Good Clinical Practice (ICH_GCP) clinical trial, approved by the Research Ethics Committee of the Capital Region of Denmark (Journal-nr.:H-18012490, date of approval: 18 June 2018) and the Danish Medicines Agency (EudraCT no. 2018-000726-63, date of approval: 6 June 2018). The GCP unit in Eastern Denmark has carried out regular monitoring of the trial according to GCP (ID: 2018-1050).

Dopamine activity has been associated with the response to antipsychotic treatment. Our study used a four-parameter model to test the association between the striatal decarboxylation rate ofSixty-two individuals (31 patients and 31 control subjects) underwentHigh baseline decarboxylation rates (kStriatal decarboxylation rate at baseline was associated with psychotic symptoms and treatment response. The strong association between k

Purpose Chemotherapy-induced peripheral neuropathy (CIPN) is a recognized adverse effect of standard (neo)adjuvant chemotherapy in breast cancer (BC) treatment. However, there is no consensus on a validated method for assessing CIPN. Heart rate variability (HRV) and vibration perception threshold (VPT) could be used as objective measures to describe CIPN. The aim of this pilot study was to investigate whether subjectively reported CIPN was associated with altered HRV and VPT in BC patients. Methods We performed a cross-sectional pilot study evaluating 30 BCE patients previously treated with chemotherapy, 26 BCE patients who did not receive chemotherapy, and 22 controls without breast cancer. Self-reported CIPN was registered for the BC patients. All participants were subjected to multi-frequency vibration analyses to determine VPT along with short ECG measurements to determine HRV measures. Results Self-reported CIPN was registered in 14 (46.6%) BC patients treated with chemotherapy. The VPT at 64 Hz (P = 0.022) and mean HR (P = 0.022) were significantly higher and the HRV measures SDNN (P = 0.023), RMSSD (P = 0.007), LF (P = 0.050) and HF (P = 0.045) were significantly lower in BC patients reporting CIPN compared to controls when adjusted for age. VPT at 64 Hz and 125 Hz were significantly higher in BC patients not reporting CIPN compared to controls when adjusted for age. Conclusion We found elevated VPT and mean HR along with decreased HRV parameters in 14 BCE patients reporting CIPN. These findings support the need for further investigation into whether HRV and vibration analysis could contribute to an objective assessment of CIPN.

Background: In patients with primary hyperparathyroidism (PHPT) locating hyperfunctioning glands (HPGs) is crucial when planning minimally invasive surgery. Dual-isotope subtraction scintigraphy with 99mTc-MIBI/123Iodide using SPECT/CT and planar pinhole imaging (Method A) has previously shown a sensitivity >93%. However, the method is costly and time consuming and entails a high radiation dose. 11C-Choline PET/CT (Method B) is an appealing candidate method unencumbered by these disadvantages. Methods: Sixty patients with newly diagnosed PHPT participated and were scanned using both methods prior to parathyroidectomy. We investigated whether sensitivities of Method A and Method B are similar in a method-to-method comparison when using surgical findings as the true location. Results: At the patient level, sensitivities were (A) 0.98 (95% CI: 0.90–1.00) and (B) 1.00 (95% CI: 0.93–1.00). At the gland level, sensitivities were (A) 0.88 (95% CI: 0.78–0.94) and (B) 0.87 (95% CI: 0.76–0.92). With a non-inferiority margin of ∆ = −0.1, we found a 1-sided p-value < 0.001. Conclusion: Our methods comparison study found that sensitivity of Method B was not inferior to Method A. We suggest that 11C-Choline PET/CT is a clinically relevant first-choice candidate for preoperative imaging of PHPT and that Method B can likely replace Method A in the near future.

Osteomalacia is a bone-demineralizing disease of adulthood, often caused by hypovitaminosis D. Current animal models of the disease mimic osteomalacia as a consequence of gastric bypass or toxic exposure to metals, but a relevant model of diet-induced osteomalacia is lacking. For that purpose, 7-month-old female Sprague Dawley rats were randomly assigned into 2 weight-stratified groups and maintained for 4 months on synthetic diets containing negligible or normal levels of vitamin D. The dietary regimen resulted in vitamin D deficiency as measured by 25-hydroxyvitamin D serum levels; however, hypovitaminosis D per se did not affect biomarkers of calcium metabolism and bone turnover, nor did it result in increased osteoid. Thus, vitamin D depletion through the diet was found to be insufficient to induce an osteomalacia-like phenotype in the adult rat. After 4 months, the phosphate content of the vitamin D–depleted diet had decreased to 0.16% (calcium:phosphorus ratio of 5.85), resulting in an osteomalacic-like condition (trabecular osteoid surface/bone surface constituted 33%; CI, 26-40). The diet change also affected both metabolic and bone turnover biomarkers, including significantly suppressing serum fibroblast growth factor 23. Furthermore, decreased dietary phosphate in a vitamin D–depleted diet led to microarchitectural changes of trabecular and cortical bone, lower bone mass density, lower bone mass content and decreased bone strength, all indicating reduced bone quality. Taken together, our results show that osteomalacia can be induced in the adult female rat by depleting vitamin D and lowering phosphate content in the diet.

BackgroundPsychotic symptoms have been linked to salience abnormalities in the brain reward system, perhaps caused by a dysfunction of the dopamine neurotransmission in striatal regions. Blocking dopamine D2 receptors dampens psychotic symptoms and normalises reward disturbances, but a direct relationship between D2 receptor blockade, normalisation of reward processing and symptom improvement has not yet been demonstrated. The current study examined the association between blockade of D2 receptors in the caudate nucleus, alterations in reward processing and the psychopathology in a longitudinal study of antipsychotic-naïve first-episode schizophrenia patients.MethodsTwenty-two antipsychotic-naïve first-episode schizophrenia patients (10 males, mean age 23.3) and 23 healthy controls (12 males, mean age 23.5) were examined with single-photon emission computed tomography using 123I-labelled iodobenzamide. Reward disturbances were measured with functional magnetic resonance imaging (fMRI) using a modified version of the monetary-incentive-delay task. Patients were assessed before and after 6 weeks of treatment with amisulpride.ResultsIn line with previous results, patients had a lower fMRI response at baseline (0.2 ± 0.5 v. 0.7 ± 0.6; p = 0.008), but not at follow-up (0.5 ± 0.6 v. 0.6 ± 0.7), and a change in the fMRI signal correlated with improvement in Positive and Negative Syndrome Scale positive symptoms (ρ = −0.435, p = 0.049). In patients responding to treatment, a correlation between improvement in the fMRI signal and receptor occupancy was found (ρ = 0.588; p = 0.035).ConclusionThe results indicate that salience abnormalities play a role in the reward system in schizophrenia. In patients responding to a treatment-induced blockade of dopamine D2 receptors, the psychotic symptoms may be ameliorated by normalising salience abnormalities in the reward system.

Background It is well known that breast cancer (BC) patients often suffer from chemotherapy-induced peripheral neuropathy (CIPN). However, it is not always recognized that they have higher risk of falling, dizziness and other signs of dysfunctional autonomous nervous system. We performed a systematic review of the literature on vibration perception threshold (VPT) and heart rate variability (HRV) as methods to objectively assess (CIPN) in BC-patients. Could VPT and HRV describe coexisting sensory and autonomic nerve damage? Materials and Methods PubMed was searched in September 2019. The included studies had to address HRV and/or VPT in BC-patients who received chemotherapy. Results Seven studies assessed VPT and six studies assessed HRV in BC-patients. Studies showed lowered perception of vibrations after chemotherapy reflected in higher VPT and no changes in HRV after taxane-based chemotherapy. No studies evaluated VPT and HRV at the same time. Conclusion The results were limited by short follow-up, small sample sizes, and different chemotherapy regimens which makes generalizability problematic. A standard assessment method of CIPN is still missing and further research is needed to evaluate if VPT and HRV could contribute to an objective assessment of CIPN. With higher survival rates for BC-patients autonomous and sensory nerve damage will be an increasing task. However, our literature review showed that no one have focused on the combination of autonomous and sensory affection measured by the simple methods VPT and HRV. Therefore, we encourage the development of international guidelines for the objective measure of nerve damage in BC-patients.

Background: Sodium-glucose co-transporter-2 inhibitors are a promising new treatment option for patients with heart failure and reduced ejection fraction (HFrEF) with and without type 2 diabetes. We investigated the effects of empagliflozin on estimated extracellular volume (ECV), estimated plasma volume, and measured glomerular filtration rate (GFR) in patients with HFrEF. Methods: Empire HF Renal was an investigator-initiated, double-blind, placebo-controlled, randomised trial with recruitment from four hospitals in Denmark. Patients in New York Heart Association class I-III, with a left ventricular ejection fraction of 40% or lower, and on guideline-directed heart failure therapy were randomly assigned (1:1) to receive either oral empagliflozin 10 mg or placebo once daily for 12 weeks. The co-primary renal outcomes were the between-group difference in the change of estimated ECV, estimated plasma volume, and measured GFR from baseline to 12 weeks. The trial is registered at ClinicalTrials.gov (NCT03198585). Findings: Between June 29, 2017, and July 15, 2019, 391 patients were screened and 120 (31%) were assigned to empagliflozin or placebo; 59 (98%) in the empagliflozin group and 58 (97%) in the placebo group were included in the analyses. Significant reductions in estimated ECV, estimated plasma volume, and measured GFR with empagliflozin versus placebo were observed [estimated ECV; adjusted mean difference of change empagliflozin versus placebo -0·12 L; 95% confidence interval (CI) -0·18 to -0·05, P=0·0006. Estimated plasma volume; -7·3%; 95% CI -10·3 to -4·3, P

BACKGROUND: Disturbances in the interacting dopaminergic, glutamatergic and GABAergic systems in the cortico-striato-thalamo-cortical circuits in the brain have been implicated in the pathophysiology of psychosis. Preclinical literature suggests that these disturbances are linked to each other, whereas recent clinical data have pointed to separate subgroups of patients characterized by either glutamatergic or dopaminergic abnormalities. In the present study we explore the associations between dopamine synthesis capacity and glutamate and GABA levels in antipsychotic-naïve first-episode psychosis (FEP) patients. METHODS: The study is ongoing. We have now processed magnetic resonance spectroscopy (MRS) and positron emission tomography (18F-FDOPA-PET) data on 22 patients (32% males, mean age 22 (±4.3)) and 18 controls (50% males, mean age 22 (±2.7)). All patients are strictly antipsychotic-naïve and have no substance abuse. The diagnosis is validated with a diagnostic interview. The patients fulfill the criteria for schizophrenia (n:15), non-organic psychosis (n:5), schizoaffective disorder (n:1) or paranoid psychosis (n:1). They are moderately ill with a mean total score of 78 (±9.6) on the Positive and Negative Syndrome Scale. Glutamate and GABA-levels in the anterior cingulate cortex (ACC) are obtained with MRS. Dopamine synthesis capacity in striatum is measured with 18F-FDOPA-PET. The mean dopamine synthesis capacity is extracted from the whole striatum. Additionally, striatal subregions are defined anatomically (nucleus accumbens, nucleus caudatus and putamen, left and right) and subregional dopamine synthesis capacities are obtained. The association between dopamine synthesis capacity and levels of glutamate and GABA in patients and controls is assessed with linear regression with dopamine synthesis capacity as dependent variable and group and GABA or glutamate as independent variables. Analyses are performed with and without adjustment for age and sex. RESULTS: High dopamine synthesis capacity in the total striatum is associated with low ACC glutamate levels in patients (p=.03), but not in controls. This association remains significant after adjusting for age and sex (p=.02). In all subjects, dopamine synthesis capacity in the left caudate is positively correlated with ACC GABA (p

Psychotic symptoms have been linked to salience abnormalities in the brain reward system, perhaps caused by a dysfunction of the dopamine neurotransmission in striatal regions. Blocking dopamine D2 receptors dampens psychotic symptoms and normalises reward disturbances, but a direct relationship between D2 receptor blockade, normalisation of reward processing and symptom improvement has not yet been demonstrated. The current study examined the association between blockade of D2 receptors in the caudate nucleus, alterations in reward processing and the psychopathology in a longitudinal study of antipsychotic-naïve first-episode schizophrenia patients.Twenty-two antipsychotic-naïve first-episode schizophrenia patients (10 males, mean age 23.3) and 23 healthy controls (12 males, mean age 23.5) were examined with single-photon emission computed tomography using 123I-labelled iodobenzamide. Reward disturbances were measured with functional magnetic resonance imaging (fMRI) using a modified version of the monetary-incentive-delay task. Patients were assessed before and after 6 weeks of treatment with amisulpride.In line with previous results, patients had a lower fMRI response at baseline (0.2 ± 0.5 v. 0.7 ± 0.6; p = 0.008), but not at follow-up (0.5 ± 0.6 v. 0.6 ± 0.7), and a change in the fMRI signal correlated with improvement in Positive and Negative Syndrome Scale positive symptoms (ρ = -0.435, p = 0.049). In patients responding to treatment, a correlation between improvement in the fMRI signal and receptor occupancy was found (ρ = 0.588; p = 0.035).The results indicate that salience abnormalities play a role in the reward system in schizophrenia. In patients responding to a treatment-induced blockade of dopamine D2 receptors, the psychotic symptoms may be ameliorated by normalising salience abnormalities in the reward system.

Background and aim: Atherosclerosis evolves or accelerates when arteries are exposed to ionizing radiation, both early and late after exposure. Radioiodine therapy of benign thyroid disease exposes the carotid arteries to 4–50 Gy, and may thereby increase the risk of atherosclerosis. Increased risk of cerebrovascular events has been reported after radioiodine therapy. This study aimed to examine whether atherosclerosis develops early or late after radioiodine therapy of benign thyroid disease. Method: Patients treated for benign thyroid disorders (nontoxic goiter, adenoma, and hyperthyroidism) were examined with ultrasound for the main outcome, carotid intima media thickness (CIMT), and for plaque presence (plaque presence only in late damage). Signs of early damage from radioiodine were studied in 39 radioiodine-treated patients, who were examined before treatment and at 1, 3, 6, and 12 months after treatment. Late changes were studied in a cross-sectional case-control design, with radioiodine-treated patients as cases (n = 193) and patients treated with surgery as controls (n = 95). Data were analyzed with repeated measurement for longitudinal data, and with multivariate regression for cross-sectional data. Results were adjusted for age, sex, cholesterol, smoking status, known atherosclerotic disease, and body mass index. Results: No changes in CIMT were found in the patients followed prospectively for one year after treatment with radioactive iodine for benign thyroid disease (p = 0.58). In the study on late effects, there was no difference in CIMT (p = 0.25) or presence of plaques (p = 0.70) between those treated with radioactive iodine and those treated with surgery (9.8 and 5.6 years since treatment, respectively). Furthermore, the level of thyrotropin (TSH) did not influence these atherosclerosis markers. Conclusion: No early changes in CIMT were detected in patients treated with radioactive iodine for benign thyroid disease. No signs of late effects of radioactive iodine on CIMT or plaque presence were found after 10 years of follow-up. The radiation to the carotid arteries by radioactive iodine therapy for benign thyroid disease may therefore have no or low effect on atherosclerotic burden of the carotid arteries in general.

Primary hyperaldosteronism (PA), known as Mb Conn, is one of the most common forms of secondary hypertension in middle-aged adults. High plasma aldosterone has been associated with severe organ damage. The unilateral aldosterone-producing adenoma (lateralized disease) is a subtype of PA, which can be fully or partly cured by adrenalectomy.Retrospective review of data from 50 patients who underwent adrenal venous sampling (AVS) was performed. Medical records, plasma renin and aldosteron, confirmatory tests and medical imaging (predominantly Computed Tomography and Magnetic Resonance Imaging) were available. Patients with lateralized disease (n = 39) underwent adrenalectomy and additional clinical data at least one year after surgery was recorded.Age and gender were widely and equally distributed (median age = 51, age span = 28-73). Patients with lateralized disease had higher blood pressure (BP) and lower serum potassium compared to patients with bilateral hyperplasia. No difference regarding age and gender distribution was detected. Despite lateralized disease diagnosed from AVS, the medical images were normal in 10 patients (28%). Follow-up of 30 patients who underwent adrenalectomy showed that six patients were cured, 17 had better BP control, five patients had no effect and one patient had higher BP but decreased number of antihypertensive drugs.PA is of equal prevalence in men and women, young and old individuals. The agreement between imaging modalities and AVS is limited, and the final diagnosis must rely on AVS. Patients prone for surgery had better BP control after adrenalectomy.

One of best validated findings in schizophrenia research is the association between blockade of dopamine D2 receptors and the effects of antipsychotics on positive psychotic symptoms. The aim of the present study was to examine correlations between baseline striatal D(2/3) receptor binding potential (BP(p)) values and treatment outcome in a cohort of antipsychotic-naïve first-episode schizophrenia patients. Additionally, we wished to investigate associations between striatal dopamine D(2/3) receptor blockade and alterations of negative symptoms as well as functioning and subjective well-being. Twenty-eight antipsychotic-naïve schizophrenia patients and 26 controls were included in the study. Single-photon emission computed tomography (SPECT) with [(123)I]iodobenzamide ([(123)I]-IBZM) was used to examine striatal D(2/3) receptor BP(p). Patients were examined before and after 6 weeks of treatment with the D(2/3) receptor antagonist amisulpride. There was a significant negative correlation between striatal D(2/3) receptor BP(p) at baseline and improvement of positive symptoms in the total group of patients. Comparing patients responding to treatment to nonresponders further showed significantly lower baseline BP(p) in the responders. At follow-up, the patients demonstrated a negative correlation between the blockade and functioning, whereas no associations between blockade and negative symptoms or subjective well-being were observed. The results show an association between striatal BP(p) of dopamine D(2/3) receptors in antipsychotic-naïve first-episode patients with schizophrenia and treatment response. Patients with a low BP(p) have a better treatment response than patients with a high BP(p). The results further suggest that functioning may decline at high levels of dopamine receptor blockade.

The level of circulating vitamin D is known to be associated with the ejection fraction in heart failure patients and studies in rats have shown that vitamin D depletion leads to increased levels of circulating norepinephrine and decreased atrial contractility. We elucidated the effects of vitamin D supplementation on the autonomous nervous system in healthy youngsters. Thirty healthy subjects aged 18-25 years were recruited based on their serum 25-hydroxyvitamin D (25[OH]D): 15 vitamin D insufficient (25[OH]D < 50 nmol/L) and 15 vitamin D sufficient (25[OH]D > 80 nmol/L) subjects. Both groups had vitamin D supplementation (30 microg/day) and were tested at baseline and after 30, 90, and 180 days. At each visit the serum 25-hydroxyvitamin D was measured and the head-up tilt test performed. Serum 25[OH]D remained stable in the vitamin D sufficient group, while the insufficient group had a significant increase (32.0-64.5 nmol/L), P < 0.0001. Despite the increase, the insufficient group did not reach the level of the vitamin D sufficient group within the 6 months observational period (96.1 vs 64.5 nmol/L), P < 0.01. Serum norepinephrine at baseline was higher in the insufficient group (mean = 1.61 nmol/L) than in the vitamin D sufficient group (mean = 0.94 nmol/L), P < 0.01, whereas the response to tilt was lower in the insufficient group (mean = 0.69 nmol/L) compared to the sufficient group (mean = 1.17 nmol/L), P < 0.01. The heart rate at rest was higher in the insufficient group (mean = 67.7 bpm) than in the vitamin D sufficient group (mean = 56.6 bpm), P < 0.01, for the three first visits. At the last visit no difference was found. The systolic and diastolic blood pressure differed between the groups after a month, with higher pressures in the insufficient group than in the sufficient group. Vitamin D supplementation modulates the sympathetic nervous system in healthy youngsters with low serum vitamin D. The observation might lead to a greater focus on possible prevention of cardiac disease later on in life by vitamin D supplementation early in life.

Background Insufficient response to antipsychotics constitutes a challenge in the treatment of patients suffering from schizophrenia. Treatment resistances have been linked to a normal striatal dopamine system. We aim to stratify antipsychotic-naïve first-episode patients based on striatal dopamine synthesis capacity (DSC) measured with positron emission tomography (PET). We hypothesize that patients who respond to treatment have an increased DSC at baseline compared to non-responders and healthy controls (HC). Methods The current data have been collected as a part of a multimodal first episode study. Patients are examined before and after 6 weeks treatment with flexible doses of Aripiprazole. PET: Dynamic scans are performed in an integrated PET-CT scanner using the tracer 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA). Duration of scanning is two times one hour, with half an hour break. Arterial blood samples are collected during the scanning sessions and provide information on the ratio between intact 18F-FDOPA and the primary metabolite. The input functions used for this data analysis are image derived based on the largest cerebral vessels and metabolite corrected. Regions of interest (ROIs) are manually drawn around the cerebellum and semi automatically around the basal ganglia. In this preliminary work, DSC values are based on Ki parameters obtained from slopes on Patlak plots. Results DSC has been measured at baseline on 16 patients (mean age 22.6 years, 5 males) and 18 HC (mean age 21.7 years, 9 males), with no significant difference in age or gender between groups. At baseline patients had a PANSS total score of 74 (SD 9.6) and GAF total score of 35 (SD 5.2). No significant difference in Ki at baseline was shown between patients and HC. Clinical follow-up data was available on 12 patients. They received a mean Aripiprazole-dose of 9.3 (SD 3.9). Paired t-test at showed a significant effect of treatment with a follow up PANSS total of 55 (SD 11.9, p

Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D metabolites. Aim: In a cross-sectional study, plasma concentrations of vitamin D metabolites, VDBP, and the calculated free vitamin D index in users and non-users of HC were compared and markers of calcium and bone metabolism investigated. Results: 75 Caucasian women aged 25–35 years were included during winter season. Compared with non-users (n = 23), users of HC (n = 52) had significantly higher plasma concentrations of 25-hydroxyvitamin D (25OHD) (median 84 interquartile range: [67–111] vs. 70 [47–83] nmol/L, p = 0.01), 1,25-dihydroxyvitamin D (1,25(OH)2D) (198 [163–241] vs. 158 [123–183] pmol/L, p = 0.01) and VDBP (358 [260–432] vs. 271 [179–302] µg/mL, p < 0.001). However, the calculated free indices (FI-25OHD and FI-1,25(OH)2D) were not significantly different between groups (p > 0.10). There were no significant differences in indices of calcium homeostasis (plasma concentrations of calcium, parathyroid hormone, and calcitonin, p > 0.21) or bone metabolism (plasma bone specific alkaline phosphatase, osteocalcin, and urinary NTX/creatinine ratio) between groups. In conclusion: Use of HC is associated with 13%–25% higher concentrations of total vitamin D metabolites and VDBP. This however is not reflected in indices of calcium or bone metabolism. Use of HC should be considered in the interpretation of plasma concentrations vitamin D metabolites. View Full-Text

External fractionated radiotherapy of cancer increases the risk of cardio- and cerebrovascular events, but less attention has been paid to the potential side effects on the arteries following internal radiotherapy with radioactive iodine (RAI), i.e. 131-iodine. About 279 per million citizens in the western countries are treated each year with RAI for benign thyroid disorders (about 140,000 a year in the EU), stressing that it is of clinical importance to be aware of even rare radiation-induced side effects. In order to induce or accelerate atherosclerosis, the dose to the carotid arteries has to exceed 2 Gy which is the known lower limit of ionizing radiation to affect the endothelial cells and thereby to induce atherosclerosis.To estimate the radiation dose to the carotid arteries following RAI therapy of benign thyroid disorders.Assuming that the lobes of the thyroid gland are ellipsoid, that the carotid artery runs through a part of the lobes, that there is a homogeneous distribution of RAI in the lobes, and that the 24 h RAI uptake in the thyroid is 35 % of the (131)I orally administrated, we used integrated modules for bioassay analysis and Monte Carlo simulations to calculate the dose in Gy/GBq of administrated RAI.The average radiation dose along the arteries is 4-55 Gy/GBq of the (131)I orally administrated with a maximum dose of approximately 25-85 Gy/GBq. The maximum absorbed dose rate to the artery is 4.2 Gy/day per GBq (131)I orally administrated.The calculated radiation dose to the carotid arteries after RAI therapy of benign thyroid disorder clearly exceeds the 2 Gy known to affect the endothelial cells and properly induce atherosclerosis. This simulation indicates a relation between the deposited dose in the arteries following RAI treatment and an increased risk of atherosclerosis and subsequent cerebrovascular events such as stroke.

Measurements of cerebral blood flow (CBF) show large variability among healthy subjects. The aim of the present study was to investigate the relative effect of established factors influencing CBF on the variability of resting CBF. We retrospectively analyzed spontaneous variability in 430 CBF measurements acquired in 152 healthy, young subjects using 133Xe single-photon emission computed tomography. Cerebral blood flow was correlated positively with both end-tidal expiratory PCO2 (PETCO2) and female gender and inversely with hematocrit (Hct). Between- and within-subject CO2 reactivity was not significantly different. Including PETCO2, Hct and gender in the model reduced between-subject and within-subject variance by 14% and 13.5%, respectively. Withinsubject variability was mainly influenced by PETCO2 and between-subject variability mostly by Hct, whereas gender appeared to be of little added value when Hct was also accounted for. The present study confirms large between-subject variability in CBF measurements and that gender, Hct, and PETCO2 explain only a small part of this variability. This implies that a large fraction of CBF variability may be due to unknown factors such as differences in neuron density or metabolism that could be subject for further studies.

Background Very few studies have investigated the determinants of circulating 25-hydroxyvitamin D (25[OH]D) in young adults (18–25 years old) using a set of variables that include lifestyle, sociodemographic, and anthropometric data. Our aim was to investigate the association between these variables and vitamin D status in a sample of untreated young adults. Methods A total of 738 young adults were enrolled in a (June cross-sectional study 2012 to May 2014) and were recruited from educational institutions in the Copenhagen area. For multivariate logistic regression subjects was categorized based on 25[OH]D in serum into; vitamin D sufficiency (S-25[OH]D > 50 nmol/L), vitamin D insufficiency (25 nmol/L ≤ S-25[OH]D ≤ 50 nmol/L), vitamin D deficiency (S-25[OH]D

Background: The performance of elite breath hold divers (BHD) includes static breath hold for more than 11 minutes, swimming as far as 300 m, or going below 250 m in depth, all on a single breath of air. Diving mammals are adapted to sustain oxidative metabolism in hypoxic conditions through several metabolic adaptations, including improved capacity for oxygen transport and mitochondrial oxidative phosphorylation in skeletal muscle. It was hypothesized that similar adaptations characterized human BHD. Hence, the purpose of this study was to examine the capacity for oxidative metabolism in skeletal muscle of BHD compared to matched controls. Methods: Biopsies were obtained from the lateral vastus of the femoral muscle from 8 Danish BHD and 8 non-diving controls (Judo athletes) matched for morphometry and whole body VO2max. High resolution respirometry was used to determine mitochondrial respiratory capacity and leak respiration with simultaneous measurement of mitochondrial H2O2 emission. Maximal citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HAD) activity were measured in muscle tissue homogenates. Western Blotting was used to determine protein contents of respiratory complex I-V subunits and myoglobin in muscle tissue lysates. Results: Muscle biopsies of BHD revealed lower mitochondrial leak respiration and electron transfer system (ETS) capacity and higher H2O2 emission during leak respiration than controls, with no differences in enzyme activities (CS and HAD) or protein content of mitochondrial complex subunits myoglobin, myosin heavy chain isoforms, markers of glucose metabolism and antioxidant enzymes.Conclusion: We demonstrated for the first time in humans, that the skeletal muscles of BHD are characterized by lower mitochondrial oxygen consumption both during low leak and high (ETS) respiration than matched controls. This supports previous observations of diving mammals demonstrating a lower aerobic mitochondrial capacity of the skeletal muscles as an oxygen conserving adaptation during prolonged dives.

Fermented milk (FM) with putative antihypertensive effect in humans could be an easy applicable lifestyle intervention against hypertension. The mode of action is supposed to be through active milk peptides, shown to possess in vitro ACE-inhibitory effect. Blood pressure (BP) reductions upto 23 mm Hg have been reported in spontaneously hypertensive rats fed FM. Results from human studies of the antihypertensive effect are inconsistent. However, many studies suffer from methodological weaknesses, as insufficient blinding and the use of office BP measurements. We conducted a randomised, double-blind placebo-controlled study of the antihypertensive effect of Lactobacillus helveticus FM in 94 prehypertensive and borderline hypertensive subjects. The participants were randomised into three treatment groups with a daily intake of 150 ml of FM, 300 ml of FM or placebo (chemically acidified milk). The primary outcome was repeated 24-h ambulatory BP measurements. There were no statistically significant differences in the outcome between the groups (systolic BP (SBP), P=0.9; diastolic BP (DBP), P=0.2). However, the group receiving 300 ml FM had reduced BP across the 8-week period in several readings, which could be compatible with a minor antihypertensive effect. Heart rate and lipids remained unchanged between groups. Hence, our study does not support earlier studies measuring office BP-measurements, reporting antihypertensive effect of FM. Based on straight performed 24-h ambulatory BP measurements, milk fermented with Lactobacillus helveticus does not posses significant antihypertensive effect.

It is important to find a reliable and bedside method, which can estimate the cerebral blood flow (CBF) of patients in clinical settings. Estimation of CBF by calculating a blood flow index (BFI) using continuous wave near-infrared spectroscopy (CW-NIRS) and indocyanine green (ICG) as an i.v. tracer has been proposed to be a feasible and promising method. To validate if the BFI method can detect relative changes in CBF we compared data with the established method (133)Xenon single photon emission computer tomography ((133)Xe-SPECT).Ten healthy subjects were investigated before and after a bolus of acetazolamide. NIRS data were obtained using a multi source detector separation configuration in order to assess a corrected BFI (BFI(corr)) value, which attempts to eliminate contamination of skin blood flow.Data obtained showed no significant correlation between CBF changes measured by (133)Xe-SPECT and BFI(corr) (0.133, P = 0.732). After acetazolamide, a 49% increase in CBF was detected using the (133)Xe-SPECT method, whereas no changes in any ICG variables were observed after acetazolamide.The study shows that it is not possible to obtain reliable BFI data, which reflect changes in CBF after acetazolamide infusion, using the CW-NIRS and ICG method.

— The aminoterminal propeptide of type III procollagen is extracted from the circulation by the liver, and PIIINP is found in bile. This study was performed in order to investigate whether biliary excretion contributes substantially to the hepatic extraction of circulating PIIINP. Hepatic extraction before and during a 4-h period after ligation of the common bile duct was assessed from serum PIIINP concentrations in a systemic artery, the portal vein and a hepatic vein of seven healthy anaesthetized pigs. Seven sham-operated anaesthetized pigs served as controls. Ligation of the bile duct did not cause a decrease in the hepatic extraction ratio of circulating PIIINP. The PIIINP serum levels of the cholestatic pigs and of the controls were similar throughout the investigation period. The PIIINP concentrations in bile were only 10% of the corresponding serum values. Gel filtration of sera showed that the lower PIIINP concentration in the hepatic vein, as compared to the artery and the portal vein was due to a selective decrease in the concentration of the intact propeptide. The study shows that biliary excretion does not contribute significantly to the hepatic extraction of circulating PIIINP in the normal liver. Furthermore, the hepatic extraction of circulating PIIINP preferentially affects the intact propeptide, rather than the somewhat larger PIIINP related molecule in serum.

Recently introduced iterative reconstruction algorithms with resolution recovery (RR) and noise-reduction technology seem promising for reducing scan time or radiation dose without loss of image quality. However, the relative effects of reduced acquisition time and reconstruction software have not previously been reported. The aim of the present study was to investigate the influence of reduced acquisition time and reconstruction software on quantitative and qualitative myocardial perfusion single photon emission computed tomography (SPECT) parameters using full time (FT) and half time (HT) protocols and Evolution for Cardiac Software. We studied 45 consecutive, non-selected patients referred for a clinically indicated routine 2-day stress/rest 99mTc-Sestamibi myocardial perfusion SPECT. All patients underwent an FT and an HT scan. Both FT and HT scans were processed according to our standard procedure with both ordered-subset expectation maximization (OSEM) + filtered back projection (FBP) reconstructions and a second reconstruction of HT scans was performed with the RR software producing three datasets for each patient for visual analysis (FT-OSEM, HT-OSEM, and HT-RR) and for quantitative analysis (FT-FBP, HT-FBP, and HT-RR). The datasets were analyzed using commercially available QGS/QPS software and read by two observers evaluating image quality and clinical interpretation. Image quality was assessed on a 10-cm visual analog scale score. HT imaging was associated with loss of image quality that was compensated for by RR reconstruction. HT imaging was also associated with increasing perfusion defect extents, an effect more pronounced using RR than FBP reconstruction. Compared to standard FT-FBP, HT-RR significantly reduced left ventricular volumes whereas HT-FBP increased end-systolic volume. HT imaging had no effect on measured left ventricular ejections fraction or measures of reversibility. Image interpretation found a higher level of concordance between FT-OSEM and HT-RR than between FT-OSEM and HT-OSEM without any observable systematic effects. Use of RR reconstruction algorithms compensates for loss of image quality associated with reduced scan time. Both HT acquisition and RR reconstruction algorithm had significant effects on motion and perfusion parameters obtained with standard software, but these effects were relatively small and probably of limited clinical importance. Although no systematic effects on image interpretation were observed, the influence on diagnostic accuracy remains to be determined.

There is a need for real-time non-invasive, continuous monitoring of cerebral blood flow (CBF) during surgery, in intensive care units and clinical research. We investigated a new non-invasive hybrid technology employing ultrasound tagged near infrared spectroscopy (UT-NIRS) that may estimate changes in CBF using a cerebral blood flow index (CFI). Changes over time for UT-NIRS CFI and 133Xenon single photon emission computer tomography (133Xe-SPECT) CBF data were assessed in 10 healthy volunteers after an intravenous bolus of acetazolamide. UT-NIRS CFI was measured continuously and SPECT CBF was measured at baseline, 15 and 60 min after acetazolamide. We found significant changes over time in CFI by UT-NIRS and CBF by SPECT after acetazolamide (P ≤ 0.001). Post hoc tests showed a significant increase in CFI (P = 0.011) and SPECT CBF (P < 0.001) at 15 min after acetazolamide injection. There was a significant correlation between CFI and SPECT CBF values (r = 0.67 and P ≤ 0.033) at 15 min, but not at 60 min (P ≥ 0.777). UT-NIRS detected an increase in CFI following an acetazolamide bolus, which correlated with CBF measured with 133Xe-SPECT. This study demonstrates that UT-NIRS technology may be a promising new technique for non-invasive and real-time bedside CBF monitoring.

The objective of the study was to monitor collagen metabolism after thrombolytic therapy. Sequential measurements of serum aminoterminal type-III procollagen propeptide (S-PIIINP) and carboxyterminal type-I procollagen propeptide (S-PICP) were made in 62 patients suspected of acute myocardial infarction and receiving thrombolytic therapy. Regardless of whether acute myocardial infarction was confirmed or not, S-PIIINP increased (94-120%) 4 h after streptokinase therapy (por = 0.02), and decreased during the next 20 h with median values at 24 h still above the baseline (p0.02). With confirmed acute myocardial infarction, S-PIIINP increased from 24 h towards a plateau reached at day 2-3 (p0.01), with values still elevated at 6 months. No similar biphasic pattern was found for S-PICP, but patients with acute myocardial infarction had S-PICP above baseline at 1, 2, and 6 months (p0.05). A less pronounced S-PIIINP increase was noted with tissue-plasminogen activator than with streptokinase. Thrombolytic therapy induces collagen breakdown regardless of whether acute myocardial infarction is confirmed or not. With confirmed acute myocardial infarction collagen metabolism is altered for at least 6 months. Furthermore, fibrin-specific and nonspecific thrombolytic agents appear to affect collagen metabolism differently.

Pregnancy and lactation cause major changes in calcium homeostasis and bone metabolism. This population-based cohort study presents the physiological changes in biochemical indices of calcium homeostasis and bone metabolism during pregnancy and lactationWe describe physiological changes in calcium homeostasis, calcitropic hormones and bone metabolism during pregnancy and lactation.We studied 153 women planning pregnancy (n=92 conceived) and 52 non-pregnant, age-matched female controls. Samples were collected prior to pregnancy, once each trimester and 2, 16 and 36 weeks postpartum. The controls were followed in parallel.P-estradiol (E2), prolactin and 1,25-dihydroxyvitamin D (1,25(OH)2D) increased (p0.001) during pregnancy, whereas plasma levels of parathyroid hormone (P-PTH) and calcitonin decreased (p0.01). Insulin-like growth factor I (IGF-I) was suppressed (p0.05) in early pregnancy but peaked in the third trimester. Postpartum, E2 was low (p0.05); prolactin decreased according to lactation status (p0.05). 1,25(OH)2D was normal and IGF-I was again reduced (p0.05). P-PTH and calcitonin increased postpartum. From early pregnancy, markers of bone resorption and formation rose and fall, respectively (p0.001). From the third trimester, bone formation markers increased in association with IGF-I changes (p0.01). Postpartum increases in bone turnover markers were associated with lactation status (p0.001). During lactation, plasma phosphate was increased, whereas calcium levels tended to be decreased which may stimulate PTH levels during and after prolonged lactation.The increased calcium requirements in early pregnancy are not completely offset by increased intestinal calcium absorption caused by high 1,25(OH)2D since changes in bone markers indicated a negative bone balance. The rise in bone formation in late pregnancy may be initiated by a spike in IGF-I levels. The high bone turnover in lactating women may be related to high prolactin and PTH levels, low E2 levels and perhaps increased parathyroid hormone-related protein levels.

The aminoterminal propeptide of type III procollagen (PIIINP) in serum is employed as a direct marker of fibrillogenesis. The balance between local fibrillogenesis and serum PIIINP is governed by the transport and possible degradation en route from tissue to circulation. In conscious pigs, we investigated the transport of PIIINP from the knee cavity into the circulation after intra-articular injection of radiola-belled PIIINP followed by sequential sampling of thoracic duct lymph, serum and urine. Clearance from the joint space was evaluated by external detection of 131I-HSA, used as co-tracer. Lymph samples were gel filtrated to assess possible lymphatic degradation of the intact PIIINP. 125I-PIIINP and 131I-HSA were found in thoracic duct lymph within 20 min of the intra-articular injection. Both isotopes had a biphasic appearance, with the first peak after 60 min and a larger peak after 150 min. During the 6 h observational period 18% of the injected PIIINP was found in the lymph. Gel chromatography of lymph showed the fast formation of a small fraction with a lower MW than that of PIIINP, which suggests that some degradation of PIIINP may occur through the lymphatics. The half-life of the joint clearance of HSA by bulk flow was assessed to be 8.3 h. The clearance of PIIINP from the joint was estimated to be equal to that of HSA, which indicates that PIIINP leaves the joint space by bulk flow as has been proposed for HSA. Whereas the fractional amount of PIIINP in lymph and blood was lower than that of HSA, in urine the fractional amount of PIIINP was substantially higher than that of HSA. This may be the outcome of a more rapid irreversible degradation of PIIINP than of HSA. We conclude that I) PIIINP is cleared from the joint space by bulk flow; 2) degradation of PIIINP en route to the circulation cannot be excluded, but is less than 10%, and 3) after disappearing from the joint, PIIINP is distributed in body compartments in a ratio different from that of HSA. Our observations suggest that serum PIIINP may be used as a marker of fibrillogenesis in normal organisms.

The amino-terminal propeptide of type III procollagen (PIIINP, M(r) 42,000) is a promising marker for the formation of type III collagen of granulation tissue in experimental and clinical studies. The disposal kinetics of circulating PIIINP is, however, almost unknown. In conscious pigs with a thoracic duct-venous shunt, 125I-labeled PIIINP was injected intravenously. The initial distribution volume was 2.2 liters, which was 1.7 times the plasma volume (P < 0.01). The disappearance curve was three-phased, with an initial steep decline (t1/2 58 min), followed by two slower phases (t1/2 239 min and 289 h). Consecutive gel filtrations showed that the initial slope of the plasma disappearance curve corresponded to the plasma clearance of the intact PIIINP. The initial plasma clearance was 26.5 ml plasma/min, whereas the urinary clearance was 8.7 ml plasma/min (P < 0.01). The other components of the plasma disappearance curve originated from the formation and disappearance of a high and a low molecular weight (MW) fraction as part of the degradation of PIIINP. The high MW fraction (approximately M(r) 90,000) was similar to a previously described, but not further characterized, PIIINP immunoreactive component. The existence of the low MW fraction (approximately M(r) 20,000) has not been reported before. The lymphatic recirculation of intact PIIINP was rapid, and the lymph-serum ratio was almost constant within 1 h of injection. We conclude that the t1/2 of circulating PIIINP is 58 min, that PIIINP escapes the circulation very quickly, and that the degradation of PIIINP includes at least two intermediary steps.

Dual energy X-ray absorptiometry (DEXA) is the most accurate method and thus the method of choice for diagnosing osteoporosis. Due to the limited access to DEXA-scanners, screening of patients with low energy fractures (LEF) for osteoporosis is not routinely performed in Denmark. Pre-screening with a simple, less expensive device might be able to exclude patients with normal bone mineral density (BMD) from further DEXA-scans. We aimed to determine the frequency of osteoporosis in patients with LEF, and evaluate the diagnostic impact of a radiographic absorptiometry (RA) scanner in the casualty department of a major Danish county hospital. In a 5-month period, 136 adult patients with LEF were invited for BMD measurements. In 74 (54%) patients DEXA-scans (spine and femoral neck) and phalangeal RA-scans were performed. A total of 86% of the patients were female and 39% were suffering from osteoporosis (T-scoresor = -2.5) according to the DEXA results. RA-BMD and T-scores differed significantly between the two groups, with and without osteoporosis (p0.001). Comparing T-scores from RA with the lowest T-scores from DEXA, a highly significant correlation was found for women (R = 0.7, p0.001). Using a RA cut-off value (T-score-1) for women ensuring 100% sensitivity for identifying women with osteoporosis, the positive predictive value was 46%. Up to 19% of DEXA-scans could be avoided in this setting. In our population the simple RA-BMD-method was cost-effective as a pre-screening tool for osteoporosis in women. However, the final diagnosis still relies on results from DEXA-scans.

Summary Objective: Milk fermented by lactic acid bacteria is suggested to have antihypertensive effect in humans. In vitro and animal studies have established an angiotensin-converting enzyme (ACE) inhibitor effect of peptides in fermented milk. However, other modes of action must be considered, because until today no human studies have confirmed an ACE inhibition in relation to the intake of fermented milk. Materials and methods: We undertook a double-blinded randomized placebo-controlled study including 94 borderline-hypertensive persons to study the effect on human physiology of Lactobacillus helveticus fermented milk. The subjects were randomized into three groups: Cardi04-300 ml, Cardi04-150 ml or placebo. All components of the renin–angiotensin–aldosterone system were measured several times. Sympathetic activity was estimated by plasma noradrenaline and cardiovascular response to head-up tilt at baseline and after 8 weeks of intervention. Results: No ACE inhibition of the fermented milk was demonstrated, as none of the components of the renin–angiotensin–aldosteron system changed. Plasma noradrenaline response to tilt test after intervention stayed unchanged between groups (P = 0·38), but declined in the group Cardi04-300 from 2·01 ± 0·93 nmol l−1 at baseline to 1·49 ± 0·74 nmol l−1 after 8 weeks (P = 0·002). There was no change in 24-h ambulatory blood pressure or heart rate between groups. Conclusions: Despite a known ACE inhibitory effect in vitro and in animals, milk fermented with Lb. helveticus did not inhibit ACE in humans. Our results suggest that the intake of fermented milk decreases sympathetic activity, although not to an extent mediating reductions of blood pressure and heart rate in borderline-hypertensive subjects.

A noninvasive method allowing measurements of the propeptides of collagen type III (PIIINP) and type I (PICP) in ulcer washings was developed. The response to topical human growth hormone was examined. Fourteen patients with venous ulcers were treated sequentially with human growth hormone (0.1, 0.25, and 1 IU/cm2/day), each dose for 1 week, followed by 1 week washout. On alternate days, three and two times during treatment and washout periods, respectively, the ulcers were washed and incubated for 30 minutes with sterile water. No changes in healing rates in relation to growth hormone application were observed. In contrast, PIIINP increased significantly to 168% (154% to 184%) (mean, 95% confidence interval) and 195% (179% to 218%) 5 and 9 days, respectively, after start of treatment, (p < 0.01). Propeptides of collagen type I reached a significant increase, to 196% (172% to 232%), in the fourth week, (p < 0.01). The areas under the curves of PICP and PIIINP correlated significantly with the healing rates (r = 0.57, p = 0.04; and r = 0.64, p = 0.01, respectively). The authors conclude that propeptide measurements may be useful markers of healing in clinical studies.