Risk of fractures in primary hyperparathyroidism: a systematic review and meta-analysis.

An increased risk of fractures in primary hyperparathyroidism (PHPT) has been reported in a number of relatively small studies. Performing a systematic literature search, we identified available studies and calculated common estimates by pooling results from the individual studies in a meta-analysis. Searching EMBASE and PubMed, we identified published studies reporting the risk of fractures in PHPT compared to a control group. We calculated odds ratio (OR) with 95% confidence interval (CI). A total of 804 studies were identified of which 12 studies were included. Risk of any fracture was increased compared to controls (OR 2.01; 95% CI, 1.61-2.50; I2 46%, 5 studies). Analysis of fracture risk at specific sites showed an increased risk of fracture at the forearm (OR 2.36; 95% CI, 1.64-3.38; I2 0%, 4 studies) and spine (OR 3.00; 95% CI, 1.41, 6.37, I2 88%, 9 studies). Risk estimate for hip fractures was non-significantly increased (OR 1.27; 95% CI, 0.97-1.66; I2 0%, 3 studies). Risk of vertebral fractures (VFx) was also increased if analyses were restricted to only studies with a healthy control group (OR 5.76; 95% CI, 3.86-8.60; I2 29%, 6 studies), studies including patients with mild PHPT (OR 4.22; 95% CI, 2.20-8.12; I2 57%, 4 studies) or studies including postmenopausal women (OR 8.07; 95% CI, 4.79-13.59; I2 0%, 3 studies). PHPT is associated with an increased risk of fractures. Although a number of studies are limited-it seems that the risk is increased across different skeletal sites including patients with mild PHPT and postmenopausal women.

Decreased physical health-related quality of life-a persisting state for older women with clinical vertebral fracture.

In a population-based study of older Swedish women, we investigated if clinical vertebral fracture was associated with lower health-related quality of life (HRQoL) and determined whether the association remained over time. Clinical vertebral fracture was associated with lower HRQoL and the effect persisted for up to 18.9 years. INTRODUCTION: Vertebral fractures are often associated with back pain and reduced physical function, which might result in isolation and depression. As a result, women with vertebral fractures often have lower health-related quality of life (HRQoL), but during what time frame the decrease lingers is unclear. Therefore, the aim of this study was to investigate if clinical vertebral fracture and hip fracture were associated with lower HRQoL and to determine whether the associations remained over time. METHODS: Vertebral fracture assessments (VFA) were performed using dual-energy X-ray absorptiometry. Data regarding prior fractures, medications, medical history, and physical activity was collected using a questionnaire. Self-rated physical HRQoL was assessed using the 12-Item Short-Form Health Survey (SF-12). Women with clinical vertebral fractures were divided into tertiles according to time since fracture onset and their HRQoL was compared with non-fractured women. RESULTS: In a population-based cross-sectional study of 3028 women aged 77.8 ± 1.63 (mean ± SD), a total of 130 (4.3%) women reported at least one clinical vertebral fracture. Women with a clinical vertebral fracture, divided into tertiles (T1-T3) depending on time since the fracture occurred, had lower HRQoL (T1: 36.3 ± 10.8; T2: 41.0 ± 9.94; and T3:41.6 ± 11.4) than women without fracture (46.2 ± 10.6; p < 0.001). Using linear regression analysis, clinical vertebral fracture was associated with reduced physical HRQoL for up to 18.9 years, independently of covariates (age, height, weight, smoking, prior stroke, mental HRQoL, grip strength, and lumbar spine BMD). CONCLUSIONS: Clinical vertebral fracture was associated with lower self-rated physical HRQoL, for up to 18.9 years after time of fracture.

Recycling of MSWI-bottom ash in paved constructions in Sweden - A risk assessment.

This paper presents results from a risk assessment of recycling pre-treated bottom ash from municipal solid waste incineration as a subbase layer in certain asphalt paved constructions in Sweden. Based on a model for assessing environmental and health risks at contaminated areas, previously developed by the Swedish EPA and by the Swedish Geotechnical Institute, target values for total content and porewater concentrations were calculated. Three different construction sizes and geometries were considered; a 1 km long road of 10 and 20 m width, respectively, and an application of 100 × 300 m. Additionally, different technical solutions of the use of bottom as in road embankments were considered. Compared to risk assessments conducted in other countries, target values are generally higher, but in the same order of magnitude. Total lead concentrations in dust potentially emitted during construction and demolition of the bottom ash is identified as a critical factor. It requires particular attention when planning for or carrying out groundwork constructions with pre-treated bottom ash. As exposure to dust and bioavailaibility of lead in bottom ash are likely to be overestimated by the underlying risk model, higher target values for lead in bottom ash should be possible for the envisaged construction purposes without affecting the general risk level. As no data is available on actual dust production and deposition by constructing and demolishing subbase layers of pre-treated bottom ash, this should be a part of future studies in order to narrow down lead target values.

The effects of person-centered or other supportive interventions in older women with osteoporotic vertebral compression fractures-a systematic review of the literature.

Vertebral compression fracture (VCF) is a common fragility fracture and the starting point of a lasting, painful, disabling condition. The aim was to summarize evidence of person-centered/non-medical interventions supporting women with VCF. Results show small numbers of studies with only probable effect on function, pain, QoL, fear of falling, and psychological symptoms. The vertebral compression fracture (VCF) caused by osteoporosis is the third most common fragility fracture worldwide. Previously, it was believed that the pain caused by VCF was self-subsiding within weeks or a few months post-fracture. However, this positive prognosis has been refuted by studies showing that, for the great majority of patients, the VCF was the starting point of a long-lasting, severely painful, and disabling condition. The low number of studies focusing on the experience of the natural course of VCF, and what support is available and how it is perceived by those affected, calls for further investigation. Strengthening older patients' sense of security and increasing confidence in their own abilities are of great importance for successful rehabilitation following VCF. More research is needed to identify resources, possibilities, and strategies that can assist older patients to reach their goals to improve well-being. The purpose of this systematic review was to identify and summarize the current evidence of person-centered or other structured non-medical/non-surgical interventions supporting older women after experiencing an osteoporotic VCF. A systematic literature search was conducted on the MeSH terms encompassing osteoporosis and vertebral compression fractures in the PubMed-MEDLINE and Cumulative Index for Nursing and Allied Health Literature (CINAHL) databases during March through June 2015. The initial search identified 8789 articles, but only seven articles (six randomized controlled trials and one observational study with a control group) met the inclusion criteria. It became evident from the current study that the availability of evidence on the effects of non-medical interventions aiming to support older women with VCF is limited, to say the least. The trials included in this review have few limitations and were mainly considered to be of moderate quality. This systematic literature review suggests that non-medical interventions aiming to support older women with VCF might decrease levels of pain and use of analgesic as well as promote improved physical mobility and function. These interventions would probably result in an improved difference in experiences of fear of falling and perceived psychological symptoms, but would only slightly improve quality of life. However, given the nature of the seven studies, potential biases in patient selection, issues around precision with small cohorts, and failure to control for confounders, makes it difficult to draw a definitive conclusion about the significant effects of non-medical interventions. Incurring a VCF is a complex and diverse event, necessitating equally complex interventions to identify new ways forward. However, to date, interventions struggle with a risk of selection bias in that only the needs of the healthiest of the population are addressed and the voices of the remaining majority of the people affected by VCF are unheard.

A painful, never ending story: older women's experiences of living with an osteoporotic vertebral compression fracture.

UNLABELLED: Vertebral compression fractures (VCF) cause pain and decreased physical ability, with no known well-established treatment. The aim of this study was to illuminate the experience of living with a VCF. The results show that fear and concerns are a major part of daily life. The women's initial contact with health-care providers should focus on making them feel acknowledged by offering person-centered and tailored support. INTRODUCTION: In the past decade, osteoporotic-related fractures have become an increasingly common and costly public health problem worldwide. Vertebral compression fracture (VCF) is the second most common osteoporotic fracture, and patients with VCF describe an abrupt descent into disability, with a subsequent desire to regain independence in everyday life; however, little is known of their situation. The aim of this study was to illuminate the lived experience of women with an osteoporotic VCF. METHODS: Ten women were interviewed during 2012-2013, starting with an open-ended question: could you tell me what it is like to live with a vertebral compression fracture? The verbatim transcribed interviews were analyzed using a phenomenological hermeneutical approach. RESULTS: The narrative provided descriptions of living in turmoil and chaos, unable to find stability in their life with little improvement regarding pain and physical function. Shifts from periods of constant pain to periods of fear of constant pain created a loss of confidence and an increased sense of confinement. The structural analysis revealed fear and concerns as the most prominent experience building on five themes: struggling to understand a deceiving body, breakthrough pain fueling fear, fearing a trajectory into isolation, concerns of dependency, and fearing an uncertain future. CONCLUSIONS: Until researchers find a successful prevention or medical/surgical treatment for osteoporotic VCFs, health-care providers and society abandon these women to remain in a painful and never ending story.

Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance.

BACKGROUND/OBJECTIVES: Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. SUBJECTS/METHODS: Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. RESULTS: Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R(2)=0.751, P<0.001). CONCLUSIONS: During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance.

Monitoring meticillin resistant Staphylococcus aureus and its spread in Copenhagen, Denmark, 2013, through routine whole genome sequencing.

Typing of meticillin resistant Staphylococcus aureus (MRSA) by whole genome sequencing (WGS) is performed routinely in Copenhagen since January 2013. We describe the relatedness, based on WGS data and epidemiological data, of 341 MRSA isolates. These comprised all MRSA (n = 300) identified in Copenhagen in the first five months of 2013. Moreover, because MRSA of staphylococcal protein A (spa)-type 304 (t304), sequence type (ST) 6 had been associated with a continuous neonatal ward outbreak in Copenhagen starting in 2011, 41 t304 isolates collected in the city between 2010 and 2012 were also included. Isolates from 2013 found to be of t304, ST6 (n=14) were compared to the 41 earlier isolates. In the study, isolates of clonal complex (CC) 22 were examined in detail, as this CC has been shown to include the hospital-acquired epidemic MRSA (EMRSA-15) clone. Finally, all MRSA ST80 were also further analysed, as representatives of an important community-acquired MRSA in Europe. Overall the analysis identified 85 spa-types and 35 STs from 17 CCs. WGS confirmed the relatedness of epidemiologically linked t304 neonatal outbreak isolates. Several non-outbreak related patients had isolates closely related to the neonatal isolates suggesting unrecognised community chains of transmission and insufficient epidemiological data. Only four CC22 isolates were related to EMRSA-15. No community spread was observed among the 13 ST80 isolates. WGS successfully replaced conventional typing and added information to epidemiological surveillance. Creation of a MRSA database allows clustering of isolates based on single nucleotide polymorphism (SNP) calling and has improved our understanding of MRSA transmission.

Preoperative CT angiography versus Doppler ultrasound mapping of abdominal perforator in DIEP breast reconstructions: A randomized prospective study.

Is there a difference in surgery time and complication rate when Doppler ultrasound (US) is used for the preoperative mapping of perforators in comparison with computer tomography angiography (CTA)? Women who were candidates for breast reconstruction using the deep inferior epigastric perforator (DIEP) free flap were enrolled in a prospective randomized study. The operating time was 249 ± 62 min (mean ± SD) in the CTA group (n = 32) and 255 min ± 75 in the US group (n = 31)--hence a difference of 6 min on average. No flaps were lost. Sixteen complications occurred in 15 patients: seven in the CTA group and nine in the US group. Complications were remedied without delay and all patients came through with a favorable reconstruction. Preoperative mapping of perforators with US is satisfactory enough provided the microsurgery team has proper experience in breast reconstruction with the DIEP flap.

Tagging fast neutrons from an (241)Am/(9)Be source.

Shielding, coincidence, and time-of-flight measurement techniques are employed to tag fast neutrons emitted from an (241)Am/(9)Be source resulting in a continuous polychromatic energy-tagged beam of neutrons with energies up to 7MeV. The measured energy structure of the beam agrees qualitatively with both previous measurements and theoretical calculations.

Angiogenic factors in relation to clinical effect in a phase II trial of weekly paclitaxel.

BACKGROUND: Several anticancer agents including paclitaxel have an inhibitory effect on angiogenesis. AIMS: To compare the overall response rate and time to progression with changes in circulating angiogenic factors during palliative treatment with weekly paclitaxel. MATERIAL AND METHODS: Patients with metastatic BC, ECOG 0-2, received weekly paclitaxel, concomitant with trastuzumab if HER2+ BC (n = 7). Circulating vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were determined at base-line and before start of new course. RESULTS: Fifty-five of 63 included patients were evaluable. The overall response rate including stable disease ≥24 weeks (CR + PD + SD) was obtained in 25 of the evaluable patients (45%). The median time to progression (TTP) was 5.3 months and overall survival (OS) 16.7 months. Patients with triple negative breast cancer (TNBC) showed a trend towards higher base-line VEGF compared with hormone receptor positive or HER2+ tumours and had shorter TTP. Significant differences in VEGF and bFGF levels at 12 weeks were found between patients with longer versus shorter TTP (VEGF: p = 0.046, bFGF: p = 0.005) and between patients gaining versus lacking clinical benefit (VEGF: p = 0.05, bFGF: p = 0.02). CONCLUSIONS: The clinical utility of circulating VEGF may be a useful tool for monitoring treatment efficacy.

Neuropeptide levels in Dercum's disease (adiposis dolorosa).

Dercum's disease (adiposis dolorosa) is characterised by adiposity and chronic pain in the adipose tissue. It has been proposed that conditions encompassing chronic pain have altered concentrations of neuropeptides involved in pain transmission. The aim of this investigation was to examine whether patients with Dercum's disease have abnormal concentrations of different neuropeptides. In cerebrospinal fluid (CSF) and in plasma (P) from 53 patients with Dercum's disease substance P-like immunoreactivity (SP-LI), neuropeptide Y-like immunoreactivity (NPY-LI), ß-endorphin-like immunoreactivity (ß-END-LI), calcitonin gene-related peptidelike immunoreactivity (CGRP-LI), met-enkephalin-like immunoreactivity (m-ENK-LI), vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI), somatostatin (SOM-LI), γ2-melanocyte-stimulating hormone-like immunoreactivity (γ2-MSH-LI), and dynorphin-like immunoreactivity (DYN-LI) were measured. Three of the substances were also measured in a control group. The CSF concentration of SP was statistically significantly lower in the Dercum group than in the control group, whereas NPY-LI and b-END-LI were borderline statistically significantly lower and higher, respectively, in Dercum patients compared to controls. Compared with reference values, CSF-MSH-LI levels were slightly elevated and CSF-NPY-LI levels were slightly lowered in the Dercum group. The other substances in both CSF and plasma were within the reference values with a high degree of statistical significance. In conclusion, altered levels of neuropeptides that have previously been seen in different pain conditions cannot clearly be demonstrated in Dercum's disease.

Individually tailored treatment with epirubicin and paclitaxel with or without capecitabine as first-line chemotherapy in metastatic breast cancer: a randomized multicenter trial.

Anthracyclines and taxanes are active cytotoxic drugs in the treatment of early metastatic breast cancer. It is yet unclear whether addition of capecitabine to the combination of these drugs improves the treatment outcome. Patients with advanced breast cancer were randomized to first-line chemotherapy with a combination of epirubicin (Farmorubicin(®)) and paclitaxel (Taxol(®)) alone (ET) or in combination with capecitabine (Xeloda(®), TEX). Starting doses for ET were epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2), and for TEX epirubicin 75 mg/m(2), paclitaxel 155 mg/m(2), and capecitabine 825 mg/m(2) BID for 14 days. Subsequently, doses were tailored related to side effects. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), time to treatment failure (TTF), objective response (OR), safety and quality of life (QoL). 287 patients were randomized, 143 to ET and 144 to TEX. Median PFS was 10.8 months for patients treated with ET, and 12.4 months for those treated with TEX (HR 0.84, 95% CI 0.65-1.07, P = 0.16); median OS was 26.0 months for women in the ET versus 29.7 months in the TEX arm (HR 0.84, 95% CI 0.63-1.11, P = 0.22). OR was achieved in 44.8% (ET) and 54.2% (TEX), respectively (χ(2) 3.66, P = 0.16). TTF was significantly longer for patients treated with TEX, 6.0 months, versus 5.2 months following ET (HR 0.73, 95% CI 0.58-0.93, P = 0.009). Severe hematological side effects related to epirubicin and paclitaxel were evenly distributed between the treatment arms, mucositis, diarrhea, and Hand-Foot syndrome were significantly more frequent in the TEX arm. Toxicity-adjusted treatment with ET and TEX showed similar efficacy in terms of PFS, OS, and OR. In this trial with limited power, the addition of capecitabine to epirubicin and paclitaxel as first-line treatment did not translate into clinically relevant improvement of the outcome.

Minor amputation in patients with diabetes mellitus and severe foot ulcers achieves good outcomes.

OBJECTIVE: To analyse the outcome of minor amputations (through, or distal to, the ankle joint) in patients with diabetes. METHOD: All diabetic patients in a defined population undergoing one or more minor amputation between 1982 and 2006 were investigated according to a standardised protocol and were followed until final outcome (healing or death). A total of 410 consecutive amputations in 309 patients with a median age of 73 (32-93) years were identified. RESULTS: In 94% of amputations, deep infection (39%) and/or gangrene (55%) was present. Severe peripheral vascular disease or critical limb ischaemia was present in 61% of amputations. 261/410 (64%) of the amputations healed at a level below the ankle joint; 69/410 (17%) healed after a re-amputation above the ankle joint; in 76/410 of amputations (19%), the patient died before healing could occur. In surviving patients, 79% of the amputations healed below the ankle. Median healing time for amputations that healed below the ankle was 26 (2-250) weeks; 21% of amputations required a re-amputation above the ankle. None of the analysed parameters excluded the possibility of healing below the ankle. CONCLUSION: In this population-based survey, the goal of avoiding major amputation was achieved in almost two thirds of minor amputations, but at the price of long healing times. In almost all amputations, the patient had deep infection and/or gangrene. In spite of this, 64% of all amputations, and 79% of amputations in surviving patients, healed at a level below the ankle. This indicates that minor amputations in these patients are worthwhile. DECLARATION OF INTEREST: None.

Controlled compression and liposuction treatment for lower extremity lymphedema.

In 1987 we noticed excess adipose tissue in a patient with arm lymphedema and later, objective studies confirmed this clinical finding in patients with non-pitting arm lymphedema following breast cancer. A prospective study was begun in 1993, and its long-term results (15 years) shows overall complete reduction of the excess volume in patients with non-pitting arm lymphedema and that adipose tissue dominates the excess volume. Encouraged by these results we operated on a patient with primary and secondary elephantiasis of the leg. The edema was first transferred from a pitting to a non-pitting state by controlled compression therapy. Then liposuction was performed to remove the remaining excess adipose tissue, and complete reduction was finally achieved. The patient wears compression garments continuously and during the 11 years of followup, no recurrence has occurred. This paper explains our philosophical approach: a pitting lymphedema first should be treated conservatively to remove excess fluid, then liposuction can be performed to remove remaining excess volume bothersome to the patient.

Quality of life following liposuction and conservative treatment of arm lymphedema.

Arm lymphedema can produce an additional burden from a psychosocial point of view. Although edema reduction through treatment can be an advantage in terms of reduced weight of the arm and simplified clothing needs, the purpose of the present study was to register changes in psychosocial parameters during one year after treatment. Thirty-five patients underwent liposuction combined with postoperative CCT (Controlled Compression Therapy), while 14 received CCT alone. Edema volume and range of motion in the shoulder joint were measured and effects on quality of life were assessed with various questionnaires. Liposuction+CCT removed the arm lymphedema completely, whereas CCT alone reduced it by half. The treatments improved range of motion in the shoulder joint and patients' quality of life in relationship to the volume reduction. Liposuction+CCT improves patients' quality of life, particularly qualities related to the volume reduction and hence qualities associated with everyday activities. CCT is beneficial too, but the effect is less obvious than when combined with surgery, probably because the edema reduction is less. The consequences of arm lymphedema for more psychologically oriented qualities and social life in general seem to be less serious and we found few notable effects of treatment in these domains.

A two-year follow-up of work capacity in early rheumatoid arthritis: a study of multidisciplinary team care with emphasis on vocational support.

OBJECTIVE: To explore changes in sick leave patterns and work ability in patients with early rheumatoid arthritis (RA). The patients received active team support focusing on vocational rehabilitation, in addition to treatment with disease-modifying anti-rheumatic drugs (DMARDs). METHODS: This is an observational study of 110 patients with early RA aged 18-60 years and not permanently disabled. All patients were monitored regularly during a 2-year period by a team comprising a nurse, an occupational therapist, a physiotherapist, a rheumatologist, and a social worker. Intervention included work-site visits and rehabilitation meetings with the employer and the official from the local social insurance office in addition to DMARD treatment and different individual treatments, and support from the team members. RESULTS: The number of patients working full-time increased from 65 to 74 (14%), those with full-time work disability decreased from 37 to 13 (65%), and patients working part-time increased from 8 to 23 (65%). This change was already evident during the first year. CONCLUSION: Active vocational support in addition to DMARD treatment may prevent or delay work disability in patients with early RA.

[The EQUAL-ESTRO external quality control laboratory in France]. / Le laboratoire de contrôle de qualité externe EQUAL-ESTRO en France.

PURPOSE: The EQUAL-ESTRO laboratory was set up in 1998 to perform external audits of radiotherapy beams for all the European centres. Until the end of the year 2003, it was funded by EC projects. The external quality control is based on measurements performed with thermoluminescent dosimeters (TLD) sent by postal mail to the participating centre in order to be irradiated on axis in reference conditions and in conditions close to clinical conditions for photon and electron beams. The EQUAL-ESTRO laboratory also started in 2002, a new TLD control allowed to check the dosimetry of complex clinical fields for photon beams with multileaf collimator (MLC). New geometric and dosimetric checks have also been developed for brachytherapy. MATERIAL AND METHODS: The participating centre irradiates TLDs (7LiF: Na, mg, Ti, TLD 937 [Philitec]) in water at a dose of 2 Gy, calculated with the TPS used clinically, following the EQUAL-ESTRO protocol. RESULTS: Since the beginning of the activities, 46% of the French radiotherapy centres and 55% of the European radiotherapy centres applied to participate to the EQUAL quality control programme. In France, the EQUAL-ESTRO laboratory checked, from 1998 and June 2004, 283 photon beams, 180 electron beams and 61 photon beams with MLC. For all the French beams checks, the following results have been observed: for the photon beams, the results show that about 1% of the measured doses in the reference conditions on axis have been detected outside the tolerance level (deviation between the measured dose and the stated dose > +/- 5%) after a first or a second check. For points checked in photon beams with wedge filter, 2.5% of the beams checked show a deviation > +/- 5% after a first or a second check. For the electron beams, the check has been set up in January 1999. For the 180 electron beams checked, 5% of the measured doses in the reference conditions have been found outside the tolerance level (> +/- 5%). CONCLUSION: These results show clearly the importance of the quality control in radiotherapy in the frame of an external audit. This audit should now be a part of a quality assurance programme in the radiotherapy centres in addition to the internal quality control as planned in the French law (02/03/2004) concerning the external quality control conditions of the radiotherapy treatment units.

Effect of thyroid hormone supplementation on survival of euthyroid dogs with congestive heart failure due to systolic myocardial dysfunction: a double-blind, placebo-controlled trial.

Nineteen euthyroid dogs of 12 breeds with echocardiographic signs of dilated cardiomyopathy (DCM) and radiographic and clinical signs of congestive heart failure (CHF) were evaluated in a randomised, double-blind, and placebo-controlled study. The dogs received either thyroxine or placebo as an adjunct to digoxin, furosemide and propranolol. The group assignment of individual dogs and serum concentrations of thyroid hormones remained unknown to owners and investigators during the entire study period. Dogs were evaluated clinically and with electrocardiography (ECG), thoracic radiography, echocardiography and measurement of total thyroxine (tT4) and thyroid stimulating hormone (TSH) before beginning of the trial, and then one week, 2 months, 6 months and yearly after initial examination, and, when applicable, at the time of euthanasia. End-point of the study was euthanasia (n = 17) due to severe congestive heart failure or sudden death (n = 2). Survival times ranged from 17 to 1030 days (median 187 days) in the placebo group, and from 18 to 1000 days (median 73 days) in the treatment group. There was no statistically significant difference in survival times between the treatment group and the placebo group (p = 0.46). Post mortem and histopathologic examinations revealed the attenuated wavy fiber type of DCM in 11 dogs, and myocardial infarcts, arteriosclerosis and chronic valvular disease in one dog. In conclusion, there was a wide range in survival times of dogs treated with digoxin, furosemide and propranolol. Adding thyroid hormones to the treatment did not significantly influence survival.

The ghrelin cell: a novel developmentally regulated islet cell in the human pancreas.

OBJECTIVES: Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), was recently identified in the stomach. Ghrelin is produced in a population of endocrine cells in the gastric mucosa, but expression in intestine, hypothalamus and testis has also been reported. Recent data indicate that ghrelin affects insulin secretion and plays a direct role in metabolic regulation and energy balance. On the basis of these findings, we decided to examine whether ghrelin is expressed in human pancreas. Specimens from fetal to adult human pancreas and stomach were studied by immunocytochemistry, for ghrelin and islet hormones, and in situ hybridisation, for ghrelin mRNA. RESULTS: We identified ghrelin expression in a separate population of islet cells in human fetal, neonatal, and adult pancreas. Pancreatic ghrelin cells were numerous from midgestation to early postnatally (10% of all endocrine cells). The cells were few, but regularly seen in adults as single cells at the islet periphery, in exocrine tissue, in ducts, and in pancreatic ganglia. Ghrelin cells did not express any of the known islet hormones. In fetuses, at midgestation, ghrelin cells in the pancreas clearly outnumbered those in the stomach. CONCLUSIONS: Ghrelin is expressed in a quite prominent endocrine cell population in human fetal pancreas, and ghrelin expression in the pancreas precedes by far that in the stomach. Pancreatic ghrelin cells remain in adult islets at lower numbers. Ghrelin is not co-expressed with any known islet hormone, and the ghrelin cells may therefore constitute a new islet cell type.