Helle Damgaard Zacho

Absorption and metabolism of benzoic acid in growing pigs.

Dietary benzoic acid (BA) supplementation causes a pronounced reduction in urinary pH but only small changes in blood pH. The present study aimed to investigate the portal absorption profile, hepatic metabolism of BA, and renal excretion of hippuric acid (HA) underlying the relatively small impact of BA on systemic acid-base status. Eight growing pigs (BW = 63 +/- 1 kg at sampling) fitted with permanent indwelling catheters in the abdominal aorta, hepatic portal vein, hepatic vein, and mesenteric vein were allocated to 4 sampling blocks and randomly assigned to control (CON; nonsupplemented diet) or BA supplementation (B; control diet + 1% BA top-dressed). Feed intake was restricted to 3.6% of BW and the ration divided into 3 equally sized meals offered at 8-h intervals. Blood pH (7.465 and 7.486 +/- 0.004) and urinary pH (4.99 and 7.01 +/- 0.09) were less (P = 0.03 and P < 0.01) in B compared with CON. The arterial concentration, net portal flux, and net hepatic uptake of BA increased (P < 0.01) in B compared with CON. The net portal flux of BA increased (P < 0.01) after feeding with B, but remained positive (P < 0.01) at all sampling times (n = 8). Recovery of dietary BA as increased net portal flux and hepatic uptake of BA was 87 +/- 5% and 89 +/- 15%, respectively. The recovery of dietary BA as urinary excretion of BA and HA was 0.08 +/- 0.02% and 85 +/- 7%, respectively. It is concluded that the small impact of BA supplementation on systemic acid-base status was caused by a protracted BA absorption and efficient hepatic extraction and glycine conjugation in combination with efficient renal clearance of HA. Together, these physiological mechanisms prevented major BA and HA accumulation in body fluids.

Prospective Multicenter Study of Bone Scintigraphy in Consecutive Patients With Newly Diagnosed Prostate Cancer

Background International guidelines uniformly suggest no routine staging of bone metastasis in patients with bone scintigraphy (BS) in low-risk prostate cancer (PCa). These recommendations are based on retrospective investigations only. In addition, BS has most often been reported as a definitive investigation with no room for equivocal cases. Objective The objective of this study was to determine the diagnostic value of BS in a large cohort of consecutive patients with newly diagnosed PCa. Design, Setting, and Participants Over a period of 1.5 years in 2008 to 2009, consecutive patients with newly diagnosed PCa were enrolled in a noninterventional, multicenter, observational study. All patients had a whole-body, planar BS. Clinical history and clinical, pathological, and biochemical data were obtained from electronic patient files and questionnaires. Outcome Measurements and Statistical Analysis Bone scintigraphy was classified into 4 categories as nonmalignant, equivocal, likely malignant, or multiple metastasis. The primary end point was final imaging, which was a composite end point of BS and additional CT and MRI investigations. Results and Limitations A total of 635 eligible patients were recruited. Their median prostate-specific antigen (PSA) was 15 ng/mL, median Gleason was 7, and 80% of patients had local disease (T1 or T2). The proportion of nonmalignant BS was 61%, equivocal scans 26%, and likely or definitive metastasis 13%. A total of 154 patients had additional CT or MRI investigations. The final imaging diagnosis showed a prevalence of bone metastases in 87 (13.7%) of 635 patients. No bone metastases were observed in (1) patients with PSA of less than 10 ng/mL, independently of the clinical Tstage and Gleason score (n = 212) and (2) PSA of less than 20 ng/mL if Tstage is less than T3 and Gleason score is less than 8 (n = 97). Approximately 50% of the patients enrolled in this study met these criteria. Conclusion This is the first prospective trial to demonstrate that BS can be avoided in patients with low-risk PCa.

Incidental Detection of Thyroid Metastases From Renal Cell Carcinoma Using 68Ga-PSMA PET/CT to Assess Prostate Cancer Recurrence

Ga-PSMA PET/CT is increasingly used to assess prostate cancer. Avid Ga-PSMA uptake by thyroid cancer and renal cell carcinoma (RCC) has been reported in few cases. A 75-year-old man who received a diagnosis of RCC in 2006 and prostate cancer in 2009 presented with elevated prostate-specific antigen levels (0.7 ng/mL) following prostatectomy. Ga-PSMA PET/CT showed avid Ga-PSMA uptake in 1 pelvic and 1 retroperitoneal lymph node and focal Ga-PSMA accumulation in the thyroid. Excised retroperitoneal lymph node and thyroid tissues showed metastases from RCC, whereas the pelvic lymph node exhibited metastasis from prostate cancer.

Tissue viability imaging for assessment of pharmacologically induced vasodilation and vasoconstriction in human skin

Tissue viability imaging (TIVI) is a novel polarization spectroscopy method for assessing dermal vascular viability. The purpose of the present study was to compare TIVI with laser Doppler flowmetry (LDF) for assessment of pharmacologically induced vasodilation and vasoconstriction in human skin. Eight individual skin sites on the backs of seven healthy volunteers were randomized to receive an intradermal injection of prostaglandin E2 (PGE2, 10(-6) to 10(-9)M), norepinephrine (NE, 10(-5) to 10(-7)M), or vehicle. Vascular responses were measured by TIVI and LDF at the injection sites at 1-min intervals starting 2min before and ending 15min after the skin challenge. TIVI and LDF demonstrated significant dose-dependent and time-related vasodilator responses to PGE2 and vasoconstrictor responses to NE, respectively (p<0.001). The time course and dose-response functions for LDF and TIVI showed notable differences. Dose-response data showed a significant reduction in TIVI signal with NE 10-7M (10(-6) NE with LDF) whereas PGE2 10(-6)M was required to elicit a significant increase in TIVI signal (10(-8)M PGE2 with LDF). TIVI demonstrated relative vascular response changes of 0.79 to 1.63 of baseline values at 15min with NE 10(-5)M or PGE2 10(-6)M compared to values of 0.59 to 8.38 with LDF. There was a modest though significant correlation between relative changes in vascular responses measured by the two methods (p<0.0001, r(2)=0.521). A Bland-Altman difference plot demonstrated significant underestimation of relative increase versus baseline measured by TIVI (r(2)=0.99, p<0.0001). We conclude that TIVI polarization spectroscopy is a sensitive method for measurement of NE-induced vascular responses but that it is less sensitive than LDF for measurement of the PGE2-induced reactions.

Chronic intestinal ischaemia: diagnosis.

Chronic intestinal ischaemia is a relatively rare but very important clinical entity, which is caused by a reduction in the splanchnic blood flow, most often because of atherosclerosis. Intestinal angina is postprandial abdominal pain developing when the genuine and collateral vessels no longer are able to accommodate the postprandial increasing demand from the gastrointestinal tract and the liver. In addition, the clinical picture very often includes sitophobia and weight loss. In daily clinical practice, conventional angiography is considered as the gold standard, but ultra sonography, computerized tomography and magnetic resonance angiography are gaining momentum when investigating for chronic intestinal ischaemia. These methods depend on imaging of the stenotic vessels not taking into consideration the possibility of sufficient splanchnic perfusion in spite of severely stenotic or occluded vessels. Only a few papers address the physiological consequence of stenotic or occluded vessels – the lack of postprandial increase in splanchnic blood flow.

Large pore dermal microdialysis and liquid chromatography-tandem mass spectroscopy shotgun proteomic analysis: a feasibility study

The purpose of the present pilot study was to investigate the feasibility of combining large pore dermal microdialysis with shotgun proteomic analysis in human skin.

Functional versus radiological assessment of chronic intestinal ischaemia

Introduction:  The diagnosis chronic intestinal ischaemia (CII) is based on the clinical symptoms postprandial pain and weight loss combined with abnormal findings during angiography. Despite the well‐known poor correlation between symptoms and morphology, physiological tests are rarely performed.

Observer agreement and accuracy in the evaluation of bone scans in newly diagnosed prostate cancer

ObjectiveThe aim of the study was to assess the agreement in the interpretation of bone scintigraphy (BS) in a newly diagnosed prostate cancer. Materials and methodsA total of 635 consecutive patients had their planar whole-body BS independently reviewed by three nuclear medicine physicians and classified by two grading systems: (a) a four-category scale (1: benign; 2: equivocal; 3: most likely malignant; and 4: multiple metastases) and (b) a dichotomous scale (bone metastasis present or absent). ResultsAgreement in the same category, or with one or two categories of differences, was found in 66, 34, and 1.3% of the readings, respectively. Average &kgr;-values were 0.59, 0.72, and 0.83 for unweighted, linear, and quadratic weighted variants, respectively. Very high agreement was observed (96% of the readings) with the dichotomous scale (average &kgr;=0.87); a comparison with a final imaging diagnosis with additional CT or MRI showed a sensitivity of 83% and a specificity of 98%. BS categories 1, 3, and 4 were consistent with the final imaging diagnosis in 96–99% of cases. The prevalence of metastasis was 10% in category 2. To optimize the diagnostic characteristics, category 2 should be regarded as a separate option. ConclusionClose agreement was found among trained observers for the evaluation of BS in prostate cancer. The high level of agreement with a dichotomous scale was hampered by diagnostic misclassification. A scale with equivocal findings on planar BS is considered important to allow for additional imaging and correct staging at the bone level of BS in a population with newly diagnosed prostate cancer.

68Ga-PSMA PET/CT for the detection of bone metastases in prostate cancer: A systematic review of the published literature

68Ga‐labelled prostate‐specific membrane antigen (PSMA) is a promising PET ligand for the detection of prostate cancer. Little attention has been given to the ability of 68Ga‐PSMA PET/CT to detect malignant bone lesions and whether this approach is superior to existing bone imaging modalities.

A comprehensive safety evaluation of 68Ga-PSMA-11 PET/CT in prostate cancer the results of 2 prospective, multicenter trials

Purpose The aim of this study was to evaluate the clinical safety profile of the 68Ga-PSMA-11 ligand for PET/CT imaging in prospective clinical trials. Methods Eighty-eight patients with newly diagnosed or recurrent prostate cancer participated in 2 prospective trials. Safety reporting was identical in the 2 trials. The 68Ga-PSMA-11 ligand was administered as 2 MBq/kg body weight (mean, 9.2 &mgr;g, 9.7 nmol). The reporting of clinical adverse events (AEs) and the measurement of blood pressure (BP) and heart rate (HR) were performed prior to injection (baseline); immediately after injection of 68Ga-PSMA-11 (postinjection); at 1, 10, and 60 minutes after injection; and after acquisition of the PET/CT scan (postscan). All hemodynamic assessments were performed in the supine position, except for the postscan measurement (sitting). The patients were interviewed regarding any AEs at baseline, postinjection, or postscan. In addition, the patients were instructed to report any AEs during the investigation and to contact the investigator if AEs occurred during the rest of the day. Adverse events were classified as mild, moderate, or severe by the patients and categorized by the investigator using the CTCAE (Common Terminology Criteria for Adverse Events) version 4.0. Results There were no reported clinical AEs. There were significant decreases in systolic BP (P < 0.001) and HR (P < 0.001) over time. In comparison, the diastolic BP increased significantly (P < 0.001). After removal of the last observation (supine position), there was no time-dependent change in systolic or diastolic BP, but the significant change in HR remained. The mean changes over the entire observation period were minimal (systolic BP, −6 to 5 mm Hg; diastolic BP, −2 to 3 mm Hg; HR, decrease of 5 beats/min). No patients developed hypotension. Fifty-five patients presented with hypertension at baseline, which increased by 1 CTCAE grade in 15 patients and by 2 grades in 2 patients. A large number of cases of asymptomatic (grade 1) bradycardia were observed, primarily in patients with preexisting bradycardia. One patient developed transient grade 1 tachycardia. No patients required medical intervention for cardiovascular perturbations. Conclusions 68Ga-PSMA-11 PET/CT was very well tolerated. We consider 68Ga-PSMA-11 to be safe for human application.