Jan L. Madsen

Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and β-cell function in type 2 diabetes: a parallel-group study

BACKGROUND Glucagon-like peptide 1 (GLP-1) has been proposed as a treatment for type 2 diabetes. We have investigated the long-term effects of continuous administration of this peptide hormone in a 6-week pilot study. METHODS 20 patients with type 2 diabetes were alternately assigned continuous subcutaneous infusion of GLP-1 (n=10) or saline (n=10) for 6 weeks. Before (week 0) and at weeks 1 and 6, they underwent beta-cell function tests (hyperglycaemic clamps), 8 h profiles of plasma glucose, insulin, C-peptide, glucagon, and free fatty acids, and appetite and side-effect ratings on 100 mm visual analogue scales; at weeks 0 and 6 they also underwent dexascanning, measurement of insulin sensitivity (hyperinsulinaemic euglycaemic clamps), haemoglobin A(1c), and fructosamine. The primary endpoints were haemoglobin A(1c) concentration, 8-h profile of glucose concentration in plasma, and beta-cell function (defined as the first-phase response to glucose and the maximum insulin secretory capacity of the cell). Analyses were per protocol. FINDINGS One patient assigned saline was excluded because no veins were accessible. In the remaining nine patients in that group, no significant changes were observed except an increase in fructosamine concentration (p=0.0004). In the GLP-1 group, fasting and 8 h mean plasma glucose decreased by 4.3 mmol/L and 5.5 mmol/L (p<0.0001). Haemoglobin A(1c) decreased by 1.3% (p=0.003) and fructosamine fell to normal values (p=0.0002). Fasting and 8 h mean concentrations of free fatty acids decreased by 30% and 23% (p=0.0005 and 0.01, respectively). Gastric emptying was inhibited, bodyweight decreased by 1.9 kg, and appetite was reduced. Both insulin sensitivity and beta-cell function improved (p=0.003 and p=0.003, respectively). No important side-effects were seen. INTERPRETATION GLP-1 could be a new treatment for type 2 diabetes, though further investigation of the long-term effects of GLP-1 is needed.

Effect of nonabsorbed amounts of a fructose-sorbitol mixture on small intestinal transit in healthy volunteers.

Although malabsorption of small amounts of fructose–sorbitol mixtures occurs frequently in healthy humans, insights into their effects on gastrointestinal motility are poor. The present study addresses the hypothesis that malabsorption of a fructose–sorbitol challenge changes the small intestinal transit rate. Eleven healthy volunteers participated in a double-blind crossover investigation. In random order, the subjects ingested 30 g glucose or a mixture of 25 g fructose and 5 g sorbitol as 10% solutions. As a radiolabeled marker, 99mTc-diethylenetriaminepentaacetic acid was added to each test solution. Breath hydrogen and methane concentrations and gastrointestinal progress of the radiolabeled marker were followed for the next 6-hr period. Malabsorption of small amounts of the fructose–sorbitol mixture was evident in all subjects. The area under the gastric radioactivity–time curve after ingestion of glucose did not differ from that after ingestion of the fructose–sorbitol mixture (P = 0.7897). However, the mouth-to-cecum transit of the radiolabeled marker was faster (P = 0.0033) and the percentage content of the marker in colon was higher after ingestion of the fructose–sorbitol mixture than after ingestion of glucose (P = 0.0128). In healthy humans, malabsorption of small amounts of a fructose–sorbitol mixture accelerates small bowel transit.

The role of bone SPECT/CT in the evaluation of lumbar spinal fusion with metallic fixation devices.

Purpose: It is difficult to evaluate the stability of the lumbar spondylodesis with metallic fixation devices by conventional imaging methods such as radiography or magnetic resonance imaging. It is unknown whether single photon emission computed tomography/computed tomography (SPECT/CT) may be useful to detect a lack of fixation of the pedicle screws and hence to predict instability of the fused vertebral segments. Materials and Methods: A retrospective analysis of 9 patients who were referred to bone scintigraphy, including combined SPECT/CT, due to persistent pain or discomfort after stabilizing lumbar surgery with metallic implants. The SPECT/CT findings were compared with observations from subsequent surgical reexploration. Results: In 6 of 9 patients, the SPECT/CT fully or partially detected the vertebral level of loose pedicle screws. Of 9 cases, 2 were considered inconclusive, whereas in 1 case loose pedicle screws were detected at a wrong vertebral level. Conclusion: SPECT/CT may be useful to detect a lack of fixation of the metallic implants, and hence instability of the spondylodesis by evaluating the focal bone mineralization activity in relation to the pedicle screws.

Meal-induced changes in splanchnic blood flow and oxygen uptake in middle-aged healthy humans

Objective. For decades, the determination of changes in splanchnic blood flow and oxygen uptake after a meal has been used in the management of patients with suspected chronic intestinal ischaemia. However, little is known about the normal meal-induced responses. The aim of the present study was therefore to measure the splanchnic blood flow and oxygen uptake before and after a standardized meal in a group of middle-aged normal volunteers. Material and methods. Splanchnic blood flow and oxygen uptake were determined at baseline and after a 3600-kJ mixed meal in 8 healthy women (50–70 years) and 10 healthy men (52–76 years). Splanchnic blood flow was measured during hepatic vein catheterization by indirect Fick principle with indocyanine green as the indicator. Splanchnic oxygen uptake was calculated from splanchnic blood flow and the arteriovenous oxygen difference. Results. The meal induced a significant peak increase in splanchnic blood flow of 0.60 (0.26–1.07) l×min−1 (mean, range) from a baseline level of 1.05 (0.66–1.33) l×min−1. Splanchnic oxygen uptake showed a significant peak increase of 1.40 (0.44–4.13) mmol×min−1 from a baseline level of 2.18 (1.41–3.31) mmol×min−1. A close association was found between the meal-induced peak increases in splanchnic blood flow and oxygen uptake, but the variables were not related to gender or body surface area of the subjects. Conclusions. A 3600-kJ mixed meal induces a significant increase in splanchnic blood flow and oxygen uptake in middle-aged healthy humans. Our data may be relevant for the evaluation of corresponding data from patients with suspected chronic intestinal ischaemia.

The SNMMI and EANM Practice Guideline for Small-Bowel and Colon Transit 1.0

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. Its 18,000 members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine. In addition to publishing journals, newsletters, and books, the SNMMI also sponsors international meetings and workshops designed to increase the competencies of nuclear medicine practitioners and to promote new advances in the science of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The SNMMI/EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and to improve the quality of service to patients. Existing practice guidelines will be reviewed for revision or renewal as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI/EANM recognizes that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as described in each document. The EANM and SNMMI have written and approved these guidelines to promote the use of nuclear medicine procedures with high quality. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI/EANM cautions against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Wound spread of radiolabeled saline with multi- versus few-hole catheters.

Background and Objectives: Continuous wound infusion of local anesthetics is effective in postoperative pain management and may be useful in major joint arthroplasty, but the optimal technique for postoperative administration of local anesthetics in the wound awaits trials evaluating the optimal type of catheter (single-, few-, or multiholed catheters). Methods: Sixteen patients undergoing total hip arthroplasty were randomized to intraoperative subfascial placement of a triple-orifice epidural catheter or a 15-cm multiholed catheter. Twenty milliliters of technetium Tc 99m diethylenetriaminepentaacetic acid-labeled saline was injected postoperatively and wound spread for 10 mins was recorded with a double-head gamma camera. Results: Mean (SD) wound spread (cm2) was the same with administration through a multiholed catheter versus the epidural catheter in both anterior (89 [15] versus 82 [20], P = 0.4) and lateral (68 [19] versus 60 [11], P = 0.3) projections. Conclusions: Wound spread of a bolus injection through 15-cm multiholed catheters versus triple-orifice epidural catheters is similar with subfascial catheter placement in total hip arthroplasty. Procedure-specific trials are required to evaluate the analgesic efficacy of postoperative administration of local anesthetic in the wound with different types of catheter before general recommendations can be made.

Small-bowel permeability in collagenous colitis.

Objective. Collagenous colitis (CC) is a chronic inflammatory bowel disease that affects the colon. However, some patients with CC present with accompanying pathologic small-bowel manifestations such as coeliac disease, defects in bile acid absorption and histopathologic changes in small-intestinal biopsies, indicating that CC is a pan-intestinal disease. In small-intestinal disease, the intestinal barrier function may be impaired, and the permeability of the small intestine altered. The purpose of this research was to study small-bowel function in patients with CC as expressed by intestinal permeability. Material andmethods. Ten patients with CC and chronic diarrhoea participated in the study. Coeliac disease was excluded by small-bowel biopsy and/or serology. Intestinal permeability was assessed as urinary excretion (ratios) 2, 4 and 6 h after ingestion of 14C-labelled mannitol (14C-mannitol) and 99mTc-labelled diethylenetriamine-pentaacetic acid (99mTc-DTPA). Data were compared with the results from healthy controls. Results. No difference was found between groups in urinary excretion of 14C-mannitol and 99mTc-DTPA after 2, 4 or 6 h, respectively. Likewise, no significant differences in the 99mTc-DTPA/14C-mannitol ratios between patients and controls were detected after 2 h: 0.030 (0.008–0.130) versus 0.020 (0.007–0.030), p=0.19, after 4 h: 0.040 (0.009–0.180) versus 0.020 (0.008–0.040), p=0.14 or after 6 h: 0.040 (0.012–0.180) versus 0.020 (0.010–0.040), p=0.17. Conclusions. No alterations in intestinal permeability in patients with CC could be demonstrated. Impairment of the integrity of the mucosa of the small bowel and the presence of a general dysfunction of the small intestine in patients with CC seem unlikely.

Scintigraphic assessment of gastrointestinal motility: a brief review of techniques and data interpretation

Gastrointestinal transit reflects overall gastrointestinal motor activity and is regulated by a complex interplay between neural and hormonal stimuli. Thus, transit measurements provide a measure of the combined effects of gastrointestinal muscular activity and feedback from the gut and brain. Dysmotility in the different major segments of the gastrointestinal tract may give rise to similar symptoms; hence, localizing transit abnormalities to a specific segment is a valuable element of diagnostic evaluation. Scintigraphy is an effective noninvasive tool to assess gastric emptying as well as small intestinal and colonic transit. This article reviews current imaging techniques, methods for data processing and principles for evaluating results when scintigraphy is used to assess gastrointestinal motility. Furthermore, clinical indications for performing scintigraphy are reviewed.

Bone SPECT/CT detection of a sequestrum in chronic-infected nonunion of the tibia.

Abstract:Sequestra are dead pieces of bone most often seen in long bones affected with prior or current infection. In addition to antibiotic therapy, chronic osteomyelitis with sequestration requires surgical debridement for cure. The author presents a case of tibial fracture associated with chronic

Bone marrow perfusion in healthy subjects assessed by scintigraphy after application of a tourniquet.

By means of a gamma camera technique involving a bolus injection of autologous 99mTc-labeled erythrocytes, we found that despite a tourniquet on the limb, the erythrocytes entered the bone marrow, and caused oozing in both lower (10 subjects) and upper limbs (14 subjects). The 24 healthy volunteers, 18 men, had a mean age of 50 (range 20-86) years. The activity reached the distal femur in a median of 365 (quartile 278-560) seconds and the distal humerus in a median of 280 (quartile 208-370) seconds. The median velocity for movement of erythrocytes in the femur was 3.7 (quartile 2.7-4.4) cm/min and in the humerus, it was 4.0 (quartile 3.1-5.3) cm/min. In 21 subjects, this activity reached the periarticular soft tissue. After 15 min with the tourniquet inflated, the activity in the distal femur of the tourniquet limb was 9 (quartile 5-18)% of that in the limb without a tourniquet. This study shows that although a tourniquet effectively occludes the extra-osseous blood supply, some intra-osseous blood supply is retained, which makes it difficult to obtain a bloodless field in some patients, despite the use of a tourniquet.