Lars Højsgaard Andersen

Parathyroid glands, calcium, and vitamin D in experimental fluorosis in pigs

SummaryThe purpose of this study was to determine whether total serum calcium, parathyroid gland structure, and/or levels of parathyroid hormone, 1,25 and 24,25 DHCC, are altered in pigs with dental and skeletal fluorosis. Eight experimental animals receiving 2 mg F−/kg b.w. per day from age 8–14 months were compared with eight controls. Concentrations of plasma fluoride and total plasma calcium were assessed at intervals throughout the experiment and during a 48 hour period at day 110–111 of the experiment. At the same time, concentrations of immunoreactive parathyroid hormone were measured using a homologous labeled antibody for porcine hormone, and a radioimmunoassay was used to assess concentrations of 1,25 DHCC and 24,25 DHCC. Parathyroid tissue volumes were assessed at the end of the experiment by quantitative histology using volumetry and point counting. Plasma fluoride increased from 0.0007±0.0001 mmol/liter to 0.0127±0.002 mmol/liter in pigs receiving fluoride. In spite of this increase, total plasma calcium remained the same throughout the experiment. Volumes of parathyroid tissue, and levels of circulating parathyroid hormone 1,25 DHCC and 24,25 DHCC, were not significantly changed. It was therefore concluded that disturbance of calcium homeostasis is not an obligatory finding in dental and skeletal fluorosis and consequently does not play an essential role in the pathogenesis of these hard tissue lesions.

Effect of Electronic Monitoring on Social Welfare Dependence

Research Summary We studied the effect on social welfare dependence of serving a sentence under electronic monitoring rather than in prison using Danish registry data and two policy shifts that extended the use of electronic monitoring in Denmark. We found that electronic monitoring is less harmful than imprisonment, at least for younger offenders, whereas it does not leave older offenders worse off than imprisonment. Policy Implications As the United States moves toward noncustodial alternatives to imprisonment, policy makers might benefit from knowledge on experiences from other contexts. The experiences from Denmark are clear: Electronic monitoring is less harmful than imprisonment to the life-course outcomes of offenders. Because electronic monitoring could be less costly for the corrections administrations than imprisonment, efforts to extend the use of electronic monitoring in the United States could be accelerated.

Analgesic Treatment in Laparoscopic Gastric Bypass Surgery: a Systematic Review of Randomized Trials

This review aimed to present an overview of the randomized controlled trials investigating analgesic regimens used in laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. Literature search was performed in PubMed and EMBASE databases in August 2013 in accordance to PRISMA guidelines. The literature search identified nine studies eligible for inclusion. The administration of nonsteroidal anti-inflammatory drugs, local anesthetics (intraperitoneally or subfascially/subcutaneously), transversus abdominis plane block, dexmedetomidine, and ketamine may improve analgesia compared to placebo/controls in LRYGB. None of the studies incorporated multimodal procedure-specific analgesic regimens. The Oxford quality scoring system scores indicated a generally limited methodological quality of the included studies. This review documents a need for high-quality, procedure-specific literature concerning analgesic treatment in LRYGB surgery.

Pharmacokinetics of high‐dose intravenous melatonin in humans

This crossover study investigated the pharmacokinetics and adverse effects of high‐dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221,500.0 (185,637.5–326,175.0) pg/mL and 1,251,500.0 (864,375.0–1,770,500.0) pg/mL, respectively; mean (SD) t1/2 was 42.3 (5.6) minutes and 46.2 (6.2) minutes; mean (SD) Vd was 1.6 (0.9) L/kg and 2.0 (0.8) L/kg; mean (SD) CL was 0.0253 (0.0096) L/min · kg and 0.0300 (0.0120) L/min · kg; and median (IQR) AUC0‐∞, 8,997,633.0 (6,071,696.2–11,602,811.9) pg · min/mL and 54,685,979.4 (36,028,638.6–105,779,612.0) pg · min/mL. High‐dose intravenous melatonin did not induce sedation, evaluated as simple reaction times. No adverse effects were reported in the study.

Analgesic and antihyperalgesic effects of melatonin in a human inflammatory pain model: a randomized, double-blind, placebo-controlled, three-arm crossover study.

Abstract Antinociceptive effects of melatonin have been documented in a wide range of experimental animal models. The aim of this study was to investigate the analgesic, antihyperalgesic, and anti-inflammatory properties of melatonin using a validated burn injury (BI) model in healthy male volunteers. The design was a randomized, double-blind, placebo-controlled, three-arm crossover study. Each volunteer participated in 3 identical study sessions with intravenous administration of placebo, melatonin 10 mg, or melatonin 100 mg. Sixty minutes after bolus injection of study medication, a BI was induced by a computerized contact thermode (47.0°C, 420 seconds, 5.0 × 2.5 cm2). Pain ratings during the BI and quantitative sensory testing at baseline and at 1, 2, 4, and 6 hours after the BI were performed. Quantitative sensory testing included assessments of secondary hyperalgesia areas, mechanical and thermal thresholds in the BI area, and pressure algometry. Furthermore, markers of inflammation, skin-reflectance spectrophotometry, and high-resolution ultrasonography were applied to measure skin erythema and dermal thickness in the BI area. Pain during the BI and secondary hyperalgesia areas were defined as primary outcomes. Twenty-nine volunteers were randomized and completed the study. While the BI induced large secondary hyperalgesia areas and significantly increased the markers of inflammation, no significant effects of melatonin were observed with respect to primary or secondary outcomes, compared with placebo. The administration of melatonin was not associated with any adverse effects. Melatonin did not demonstrate any analgesic, antihyperalgesic, or anti-inflammatory properties in the BI model.

Effect of Marriage and Spousal Criminality on Recidivism

The authors analyzed whether the effect of marriage on recidivism varied by spousal criminality. For this purpose, they used propensity score matching and full population data from Statistics Denmark on all unmarried and previously convicted men from birth cohorts 1965–1985 (N = 102,839). The results showed that marriage reduced recidivism compared to nonmarriage only when the spouse had no criminal record. Similarly, marriage to a nonconvicted spouse reduced recidivism significantly more than marriage to a convicted spouse. These findings not only underline how important marriage is for social integration but also stress the heterogeneous nature of the protective effects of marriage.

Optimized Anesthesia and Analgesic Regimen for Robotic Colorectal Surgery

Robotic surgery has recently been introduced for colorectal procedures. In robotic colorectal surgery, only a few low-powered randomized studies have been performed, demonstrating equal short-term surgical outcomes. Robotic surgery offers specific technical advantages; however, studies have documented increased operative time and economic costs compared to both open and laparoscopic colorectal surgery. At the moment, no randomized studies, cohort studies or case-series have investigated outcomes related to anesthesia or analgesic treatment in robotic colorectal surgery. Experience and transferable evidence from laparoscopy and other fields of robotic surgery, such as urology and gynecology may provide valuable information when introducing this new technique. This review presents an overview of the anesthesiological challenges during robotic colorectal surgery. Furthermore, clinical recommendations are presented in relation to patient preparation, patient safety, anesthetic treatment, and postoperative pain management. This review recommends total intravenous anesthesia, including propofol and ultra-fast acting opioids. Moreover, neuromuscular blocking agents for complete (deep) block are mandatory. For postoperative analgesic treatment, a multimodal regimen including dexamethasone, paracetamol, COX-1selective NSAIDs, oral opioids is recommended. Clinical effects and the administration routes of local anesthetics must be investigated further. In general, focus of the clinician should be drawn towards the preparation phase before surgery and knowledge of the physiological changes and patient handling in relation to Trendelenburg positioning and pneumoperitoneum. Lessons learned from laparoscopic colorectal surgery can be applied with respect to anesthetic- and postoperative analgesic treatment until further evidence is provided.

Melatonin in Surgery and Critical Care Medicine

Administration of exogenous melatonin in surgical and critical care patients has been investigated for various clinical purposes. Studies have demonstrated that melatonin can be used for treatment of preoperative anxiety. The analgesic effect of melatonin is well documented in experimental studies, but still needs to be established further in human clinical studies. The sleep-regulating effects of melatonin in surgical and critical care patients remain unclear. Melatonin has been shown to reduce emergence delirium in the early postoperative period, but no evidence exists in relation to postoperative and intensive care delirium. Limited evidence exists with respect to reduction of oxidative stress in surgical patients. Melatonin has been shown to improve outcome in experimental sepsis models, but still needs to be documented further in human clinical studies. Mechanisms of actions need to be clarified and most importantly dose-response relationships should to be established within the specific procedures and indications. Finally, paramount issues remain in relation to administration form, dosage, timing of administration, and pharmacokinetics of melatonin in surgical and critical care patients.