To Alfred Deakin

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Laparoscopic adrenalectomy (LA) was first performed in Iceland in 1997. Since then, all procedures for presumed benign lesions of the adrenals have been performed laparoscopically in a single center. Compared with conventional adrenalectomy, LA appears to achieve superior results in terms of recovery, hospital stay, and morbidity. This study aimed to evaluate the results of LA in Iceland. METHODS: The hospital records of all patients who underwent LA in Iceland from 1997 through 2005 were reviewed. The preoperative diagnosis was documented, as well as the pathologic diagnosis, operative details, complications, and length of hospital stay. RESULTS: In 49 operations, 53 adrenal glands were removed from 48 patients (37 women and 11 men). The mean patient age was 53.6 years (range, 24.4-78.8 years). The left adrenal was removed from 29 patients, the right adrenal from 14 patients, and both adrenals from 5 patients. The most common indications and diagnoses included 17 nonsecreting tumors (12 adenomas, 3 hyperplasias, 1 complex adrenal cyst, and 1 hemangioma), 12 aldosteronomas (10 aldosteronomas and 2 nodular hyperplasias), and 10 pheochromocytomas (9 confirmed, 1 adrenal hyperplasia). Other indications and diagnoses were less common. The mean operative time was 168 min (range, 87-370 min) for unilateral operations and 412 min (range, 345-480 min) for bilateral operations. The mean blood loss was 117 ml (range, 0-650 ml) for unilateral operations and 200 ml (range, 0-350 ml) for bilateral operations. The complications were mild pancreatitis (n = 1), urinary tract infection (n = 1), atelectasis (n = 1), mild congestive heart failure (n = 2), and transient corneal abrasion (n = 1). No conversion to open procedure was needed. The mean tumor size was 3.5 cm (range, 1.5-6.2 cm), and the mean postoperative hospital stay was 2.6 days (range, 1-6 days). CONCLUSION: The results of laparoscopic adrenalectomies in Iceland for benign lesions of the adrenals are comparable with published results from large referral centers

To Lord Hopetoun

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldIcelandic surgeons provide a wide range of modern surgical services with excellent results. How can a nation of fewer than 300,000 persons accomplish this? The main reasons are a thriving economy, a high standard of living and education, and the training of surgeons. All Icelandic surgeons receive their training overseas, many at university hospitals in the other Nordic countries, particularly Sweden. Others receive training in the United States and Great Britain. Almost 50% of the general and orthopedic surgeons hold PhD degrees from major universities in the Nordic countries. In some other surgical subspecialties, an even greater number possess a PhD degree. This diverse background of training creates a stimulating and international outlook among the surgeons. All types of surgery are performed in Iceland, with the exception of surgery for complicated congenital heart disease and transplantation. Recently a living related renal transplant program was started with promising results

Urinary 2,8-dihydroxyadenine excretion in patients with adenine phosphoribosyltransferase deficiency, carriers and healthy control subjects.

To access publisher's full text version of this article click on the hyperlink belowBACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of adenine metabolism that results in excessive urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. The purpose of this study was to assess urinary DHA excretion in patients with APRT deficiency, heterozygotes and healthy controls, using a recently developed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) assay. METHODS: Patients enrolled in the APRT Deficiency Registry and Biobank of the Rare Kidney Stone Consortium (http://www.rarekidneystones.org/) who had provided 24-h and first-morning void urine samples for DHA measurement were eligible for the study. Heterozygotes and healthy individuals served as controls. Wilcoxon-Mann-Whitney test was used to compare 24-h urinary DHA excretion between groups. Associations were examined using Spearman's correlation coefficient (rs). RESULTS: The median (range) 24-h urinary DHA excretion was 138 (64-292) mg/24 h and the DHA-to-creatinine (DHA/Cr) ratio in the first-morning void samples was 13 (4-37) mg/mmol in APRT deficiency patients who were not receiving xanthine oxidoreductase inhibitor therapy. The 24-h DHA excretion was highly correlated with the DHA/Cr ratio in first-morning void urine samples (rs = 0.84, p < .001). DHA was detected in all urine samples from untreated patients but not in any specimens from heterozygotes and healthy controls. CONCLUSIONS: High urinary DHA excretion was observed in patients with APRT deficiency, while urine DHA was undetectable in heterozygotes and healthy controls. Our results suggest that the UPLC-MS/MS assay can be used for diagnosis of APRT deficiency.Rare Kidney Stone Consortium, a part of the National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Center for Advancing Translational Sciences (NCATS) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK

Comparison of the effect of allopurinol and febuxostat on urinary 2,8-dihydroxyadenine excretion in patients with Adenine phosphoribosyltransferase deficiency (APRTd): A clinical trial.

To access publisher's full text version of this article click on the hyperlink belowAdenine phosphoribosyltransferase (APRT) deficiency is a rare, but significant, cause of kidney stones and progressive chronic kidney disease. The optimal treatment has not been established. The purpose of this pilot study was to compare the effect of the xanthine oxidoreductase inhibitors allopurinol and febuxostat on urinary 2,8-dihydroxyadenine (DHA) excretion in APRT deficiency patients. Patients listed in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, currently receiving allopurinol therapy, were invited to participate. The trial endpoint was the 24-h urinary DHA excretion following treatment with allopurinol (400mg/day) and febuxostat (80mg/day). Urinary DHA was measured using a novel ultra-performance liquid chromatography - electrospray tandem mass spectrometry assay. Eight of the 10 patients invited completed the study. The median (range) 24-h urinary DHA excretion was 116 (75-289) mg at baseline, and 45 (13-112) mg after 14days of allopurinol therapy (P=0.036). At the end of the febuxostat treatment period, 4 patients had urinary DHA below detectable limits (<20ng/mL) compared with none of the participants following allopurinol treatment (P=0.036). The other 4 participants had a median 24-h urinary DHA excretion of 13.2 (10.0-13.4) mg at the completion of febuxostat therapy (P=0.036). Urinary DHA excretion in APRT deficiency patients decreased with conventional doses of both allopurinol and febuxostat. Febuxostat was, however, significantly more efficacious than allopurinol in reducing DHA excretion in the prescribed doses. This finding, which may translate into improved outcomes of patients with APRT deficiency, should be confirmed in a larger sample.Rare Kidney Stone Consortium, part of the Rare Diseases Clinical Research Network (RDCRN), which is an initiative of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS) NCATS National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK

Correction

To access publisher's full text version of this article click on the hyperlink belowNIDDK NIH HH

Quantitative UPLC-MS/MS assay of urinary 2,8-dihydroxyadenine for diagnosis and management of adenine phosphoribosyltransferase deficiency.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageAdenine phosphoribosyltransferase (APRT) deficiency is a hereditary disorder that leads to excessive urinary excretion of 2,8-dihydroxyadenine (DHA), causing nephrolithiasis and chronic kidney disease. Treatment with allopurinol or febuxostat reduces DHA production and attenuates the renal manifestations. Assessment of DHA crystalluria by urine microscopy is used for therapeutic monitoring, but lacks sensitivity. We report a high-throughput assay based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for quantification of urinary DHA. The UPLC-MS/MS assay was optimized by a chemometric approach for absolute quantification of DHA, utilizing isotopically labeled DHA as an internal standard. Experimental screening was conducted with D-optimal design and optimization of the DHA response was performed with central composite face design and related to the peak area of DHA using partial least square regression. Acceptable precision and accuracy of the DHA concentration were obtained over a calibration range of 100 to 5000ng/mL on three different days. The intra- and inter-day accuracy and precision coefficients of variation were well within ±15% for quality control samples analyzed in replicates of six at three concentration levels. Absolute quantification of DHA in urine samples from patients with APRT deficiency was achieved wihtin 6.5min. Measurement of DHA in 24h urine samples from three patients with APRT deficiency, diluted 1:15 (v/v) with 10mM ammonium hydroxide (NH4OH), yielded a concentration of 3021, 5860 and 10563ng/mL and 24h excretion of 816, 1327 and 1649mg, respectively. A rapid and robust UPLC-MS/MS assay for absolute quantification of DHA in urine was successfully developed. We believe this method will greatly facilitate diagnosis and management of patients with APRT deficiency.Rare Kidney Stone Consortium (U54DK083908), Rare Diseases Clinical Research Network (RDCRN), National Center for Advancing Translational Sciences (NCATS). National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK