Clinical, quality of life, and economic value of acromegaly disease control.

Although acromegaly is a rare disease, the clinical, economic and health-related quality of life (HRQoL) burden is considerable due to the broad spectrum of comorbidities as well as the need for lifelong management. We performed a comprehensive literature review of the past 12 years (1998-2010) to determine the benefit of disease control (defined as a growth hormone [GH] concentration <2.5 µg/l and insulin-like growth factor [IGF]-1 normal for age) on clinical, HRQoL, and economic outcomes. Increased GH and IGF-1 levels and low frequency of somatostatin analogue use directly predicted increased mortality risk. Clinical outcome measures that may improve with disease control include joint articular cartilage thickness, vertebral fractures, left ventricular function, exercise capacity and endurance, lipid profile, and obstructive apnea events. Some evidence suggests an association between controlled disease and improved HRQoL. Total direct treatment costs were higher for patients with uncontrolled compared to controlled disease. Costs incurred for management of comorbidities, and indirect cost could further add to treatment costs. Optimizing disease control in patients with acromegaly appears to improve outcomes. Future studies need to evaluate clinical outcomes, as well as HRQoL and comprehensive economic outcomes achieved with controlled disease.

Unintentional exposure of neonates to conventional radiography in the Neonatal Intensive Care Units.

OBJECTIVE: To evaluate the extent of unintentional exposure to X-rays performed during routine diagnostic procedures in the Neonatal Intensive Care Units (NICUs). STUDY DESIGN: During a 1-month period, 157 consecutive neonates from five level-III NICUs were recruited for this study. The mean birth weight was 1747+/-911 g (range: 564-4080 g), and gestational age was 31.6+/-3.6 weeks (range: 24-41 weeks). A total of 500 radiographs were performed including chest (68%), abdomen (17%) and combined chest and abdomen (15%). The average number of radiographs taken per infant was 4.2+/-3.6 (range: 1-21). Unintentional inclusion of body regions other than those ordered was determined by comparing the areas that should be included in the radiation field according to International recommendations, to those that appeared in the actual radiograph. RESULT: A comparison of the recommended borders to the actual boundaries of the radiographs taken show an additional exposure to radiation in all three procedures: 85% of chest radiographs also included the whole abdomen, 64% of abdomen radiographs included both thigh and upper chest and 62% of chest and abdomen radiograph included the thigh. (The range in all procedures was from ankle to upper head.) Between 2 and 20% of the relevant targeted body tissues were not included in the exposed fields resulting in missing data. The gonads of both sexes were exposed in 7% in all chest X-rays. Among male infants, the testes were exposed in 31% of plain abdomen radiographs and 34% of chest and abdomen radiographs. CONCLUSION: In the NICUs participating in the study, neonates are currently being exposed to X-ray radiation in nonrelevant body regions. Higher awareness and training of the medical teams and radiographers are required to minimize unnecessary exposure of newborns to ionizing radiation.

Comparing Effective Doses During Image-Guided Core Needle Biopsies with Computed Tomography Versus C-Arm Cone Beam CT Using Adult and Pediatric Phantoms.

PURPOSE: To compare the effective doses of needle biopsies based on dose measurements and simulations using adult and pediatric phantoms, between cone beam c-arm CT (CBCT) and CT. METHOD: Effective doses were calculated and compared based on measurements and Monte Carlo simulations of CT- and CBCT-guided biopsy procedures of the lungs, liver, and kidney using pediatric and adult phantoms. RESULTS: The effective doses for pediatric and adult phantoms, using our standard protocols for upper, middle and lower lungs, liver, and kidney biopsies, were significantly lower under CBCT guidance than CT. The average effective dose for a 5-year old for these five biopsies was 0.36 ± 0.05 mSv with the standard CBCT exposure protocols and 2.13 ± 0.26 mSv with CT. The adult average effective dose for the five biopsies was 1.63 ± 0.22 mSv with the standard CBCT protocols and 8.22 ± 1.02 mSv using CT. The CT effective dose was higher than CBCT protocols for child and adult phantoms by 803 and 590% for upper lung, 639 and 525% for mid-lung, and 461 and 251% for lower lung, respectively. Similarly, the effective dose was higher by 691 and 762% for liver and 513 and 608% for kidney biopsies. CONCLUSIONS: Based on measurements and simulations with pediatric and adult phantoms, radiation effective doses during image-guided needle biopsies of the lung, liver, and kidney are significantly lower with CBCT than with CT.

A Case Report: Cytogenetic Dosimetry after Accidental Radiation Exposure during (192)Ir Industrial Radiography Testing.

The accidental gamma radiation exposure of an industrial radiography worker and the cytogenetic examination of the worker's blood lymphocytes are described here. The exposure of the worker was due to a malfunction at the entrance into the depleted uranium-shielding device of a (192)Ir source during operation. Because the source was sealed no additional beta radiation exposure was assumed. The worker's thermoluminescent dosimeter indicated an absorbed dose of 0.078 Sv, which presumably took place in December 2013. No clinical symptoms were reported in the case history after the potential exposure to radiation. Four months after the incident it was decided that biological dosimetry using dicentric chromosome and micronucleus analysis would be performed to follow radiation protection aspects and to clarify the radiation dose uncertainties for the exposed worker. Micronucleus frequency was not increased above the laboratory's control value of micronucleus background frequency of unexposed individuals. However, the observed dicentric frequency (0.003 dicentric/cell) differs significantly from the laboratory's background level of dicentric chromosomes in unexposed individuals (0.0007 dicentric/cell). Dicentric analysis in 2,048 metaphase cells resulted in an estimated dose of no more than 0.181 Gy (95% upper confidence level), not less than 0.014 Gy (95% lower confidence level) and a mean dose of 0.066 Gy (photon-equivalent whole-body exposure) based on interpolation from the laboratory's calibration curve for (60)Co gamma radiation. Since overdispersion of dicentric chromosomes (u = 9.78) indicated a heterogeneous (partial-body) exposure, we applied the Dolphin method and estimated an exposure of 2.1 Sv affecting 21% of the body volume. Because the overdispersion of dicentric chromosomes was caused by only one heavily damaged cell containing two dicentrics, it is possible that this was an incidental finding. In summary, a radiation overexposure of the radiography worker must be assumed and this case considered as a potential partial-body exposure scenario.

Acromegaly.

Acromegaly is a slow developing disease caused by hypersecretion of growth hormone and insulin-like growth factor 1. Increased morbidity and mortality associated with the disease make early diagnosis and treatment crucial. This article reviews the etiology, clinical manifestations, and diagnosis of acromegaly, with an emphasis on newly available therapeutic options.

Early postmenopausal bone loss in hyperthyroidism.

OBJECTIVES: To evaluate the effect of hyperthyroidism on bone in relation to the menopausal state. METHODS: Fifty-nine hyperthyroid (HYPER), 40 hypothyroid (HYPO), and 51 control euthyroid (EUTH) women were studied. Bone mineral density (BMD) was assessed by dual X-rays absorptiometry (DXA) at the lumbar spine, and at the femoral neck. A multi-site QUS device evaluated speed of sound (SOS) at the radius (RAD), tibia (TIB), metatarsus (MTR), and phalanx (PLX). Bone markers used were serum bone specific alkaline phosphatase (BSAP) and urinary deoxypyridinoline (DPD). RESULTS: At all sites, SOS was lower in HYPER than in EUTH (RAD P<0.05, TIB P<0.01, MTR P<0.05, PLX P=0.01). The low SOS was only noted at the early postmenopausal period. BMD at the femoral neck but not at the lumbar spine was lower in HYPER as compared to EUTH (P<0.05). Both femoral neck and tibia were the sites with the highest odds ratio for being hyperthyroid (2.3 and 2.04, respectively). There was no correlation between BMD or SOS and FT(4), TT(3) or duration of hyperthyroidism. BSAP and DPD positively correlated with FT(4) and TT(3) (P<0.05). CONCLUSIONS: This study suggests that hyperthyroidism affects bone mineralization especially during the early postmenopausal period, and the effect is mainly at the cortical bone.

Effect of estrogen replacement therapy on speed of sound at multiple skeletal sites.

OBJECTIVES: To evaluate the effect of estrogen replacement therapy (ERT) on postmenopausal bone loss by multi-site ultrasound measurement. METHODS: A cross-sectional comparison of postmenopausal women, ERT users and non-users. The two study groups were enrolled for the reference database collection for the Sunlight Omnisense (Omnisense) and were matched by years since menopause. Speed of sound (SOS) was measured at the distal radius (RAD), mid-shaft tibia (TIB), fifth metatarsus (MTR) and proximal phalanx (PLX). RESULTS: 143 ERT users for 5.2+/-3.6 years were compared with 139 ERT non-users (age: 57.0+/-5.3 and 57.5+/-5.5, respectively). Both groups were 7.1+/-5.0 years since menopause. SOS, expressed in T-score units, was higher at the RAD in ERT users as compared to ERT non-users (-0.55+/-1.30 and -1.36+/-1.60, respectively, P<0.0001), and at the TIB (-0.73+/-1.34 and -1.28+/-1.45, respectively, P=0. 003). Same trend was observed at the MTR and PLX, but not statistically significant because of fewer observations. In early post menopause period, the ERT-non users RAD data shows an annual SOS decrease of 0.17 versus annual increase of 0.12 T-score units (P=0.037). Similar effect is observed at the TIB, though not statistically significant (non-users decrease of 0.20 vs. users increase of 0.08 T-score units/year, P=0.086). CONCLUSIONS: SOS measurements by Omnisense at multiple skeletal sites support the ERT protective effect on bone.

Bone mineral density and turnover in children with attention-deficit hyperactivity disorder receiving methylphenidate.

Attention-deficit hyperactivity disorder (ADHD) is the most common behavior disorder among children; methylphenidate is a drug frequently prescribed for the control of its symptoms. One of the potential side effects of methylphenidate that concerns parents is its impact on the growth of children, since the mechanism by which methylphenidate might influence growth is not known. As linear growth is associated with an increase in bone mineral density and turnover, this study was undertaken to evaluate bone mineral density by dual photon absorptiometry and bone turnover by measuring serum bone-specific alkaline phosphatase and the urinary deoxypyridinoline excretion rate in children treated with methylphenidate for 1 to 2 years as compared to a control group. There were no significant differences in bone mineral density at either the lumbar spine or femoral neck in the study group (0.662 +/- 0.04 and 0.735 +/- 0.07 g/cm2, respectively) as compared to the controls (0.675 +/- 0.05 g/cm2 and 0.734 +/- 0.07 g/cm2, respectively). Furthermore, there were no significant differences in serum bone-specific alkaline phosphatase in the study group (58 +/- 22 U/L) as compared to the control children (71 +/- 34 U/L) or in urinary deoxypyridinoline in the study group (34 +/- 38 nM/mM), as compared to the control group (27 +/- 12 nM/mM). In conclusion, our data do not support a significant effect of methylphenidate on bone mineral density turnover in children when used for 1 to 2 years.

An economic evaluation of the use of rare earth screens to reduce the radiation dose from diagnostic X-ray procedures in Israel.

In Israel the diffusion of rare earth screen technology has been limited. These screens could halve the radiation dose to the patient from diagnostic X-ray radiography, with little managerial effort and without being detrimental to the quality of the diagnostic image. We estimated the total effective dose from diagnostic film radiography capable of reduction by the use of rare earth screens, based on the number of hospital and ambulatory diagnostic X-ray procedures. This number was multiplied by the computed radiation dose per body site for a series of diagnostic procedures. The annual dose was approximately 0.53 mSv per head, approximately half of which could be averted by the introduction of rare earth screen technology. Based on a fatality risk of 3% Sv-1, it is estimated that the adoption of rare earth screen technology might reduce the annual incidence of cancer by some 93 cases, half of which would be fatal after an average latency period of 18.4 years. The cost of purchasing rare earth screens on a nationwide basis is approximately $3.0 million. This cost is outweighed by a saving of $9.6 million in X-ray tube replacement costs over the period 1997-2006. Government legislation enforcing the use of rare earth screens is essential, because of the lack of prestige associated with acquiring rare earth technology, as well as institutional reluctance to accept the external benefits of reduced morbidity and mortality and/or to extend budgetary time horizons.

Diagnosis of polycystic ovary disease in obese women with a 24-hour hormone profile after buserelin stimulation.

OBJECTIVE: To evaluate the 24-hour hormone response to GnRH agonist stimulation in the diagnosis of polycystic ovary disease (PCOD) in obese women. STUDY DESIGN: Forty-three obese PCOD patients and 23 controls were randomized to 1 mg buserelin (BSRL) stimulation (PCOD group P-1, n = 31; control group C-1, n = 12) or 0.1 mg (PCOD group P-0.1, n = 12; control group C-0.1, n = 11). RESULTS: Whereas following 1 mg BSRL administration, serum levels of 17 hydroxyprogesterone (17OHP), delta 4 androstenedione, estradiol (E2) and luteinizing hormone increment (delta LH) as well as the delta LH/delta follicle stimulating hormone ratio were all higher in group P-1 than in group C-1 (P < .001, < .01, < .01, = .08 and < .001, respectively), only 17OHP and E2 serum levels were higher in group P-0.1 than in group C-0.1 (P < .001, and = .01, respectively). Whereas 24-hour LH inversely correlated with body mass index (r = .37, P = .04), 24-hour hormone profile, and basal or glucose-stimulated serum insulin levels did not correlate in group P-1. CONCLUSION: The 1-mg BSRL stimulation test is a convenient diagnostic means in obesity-associated PCOD. The hormone response to BSRL administration is related to obesity, not to insulin resistance.

Androgen suppression and clinical improvement with dopamine agonists in hyperandrogenic-hyperprolactinemic women.

OBJECTIVE: To examine the effect of dopamine agonist (DA) treatment on clinical and biochemical features in hirsute, hyperprolactinemic (HPRL) women and the relationship between prolactin (PRL) and androgens. STUDY DESIGN: We evaluated 80 hirsute HPRL women (age, 27 +/- 1 years [mean +/- SE]) with neuroleptic treatment, prolactinoma and idiopathic HPRL (12, 13 and 55, respectively). DA, mainly bromocriptine, was administered for 11 +/- 1 months. Response indicators were Ferriman-Gallwey hirsutism (FGS) and Leeds acne (LAS) scores, circulating PRL, dehydroepiandrosterone sulfate (DHEAS), free and total testosterone, and androstenedione. RESULTS: Baseline PRL correlated positively with DHEAS (r = .23, P = .03) and free testosterone (r = .36, P < .001). In all women, FGS, LAS, PRL, free testosterone, DHEAS and androstenedione decreased by 40-85% during DA treatment (P < .001). The decline in free testosterone was higher when PRL was > or = 65 ng/mL than when PRL was < 65 (P = .03) and correlated positively with basal DHEAS (r = .40, P < .001). CONCLUSION: Our data suggest a modulation by PRL of adrenal androgen production. DA treatment reduces PRL and serum androgens. It results in a significant clinical improvement in acne and hirsutism. Therefore, DA is recommended as monotherapy for hyperandrogenic.

[Evaluation of radiation dose and radiation risk for dental patients].

1. The collective dental radiation dose in Israel in 1998 is 42.86 Sv. 2. The collective dental radiation is responsible for a mortality of about 2.14 people per year in Israel, and a similar number of morbidity from non-lethal cancer. 3. It seems that the quality of the picture in dental radiographs in Israel is not satisfactory, so is the dentists' level of knowledge about it. 4. Exposure to dental radiographs may be reduced by half if measures are taken to ensure the quality of the radiographs and the knowledge of dentists on the subject.

Pituitary tumor transforming gene 1 regulates Aurora kinase A activity.

Pituitary tumor transforming gene 1 (PTTG1), a transforming gene highly expressed in several cancers, is a mammalian securin protein regulating both G1/S and G2/M phases. Using protein array screening, we showed PTTG1 interacting with Aurora kinase A (Aurora-A), and confirmed the interaction using co-immunoprecipitation, His-tagged pull-down assays and intracellular immunofluorescence colocalization. PTTG1 transfection into HCT116 cells prevented Aurora-A T288 autophosphorylation, inhibited phosphorylation of the histone H3 Aurora-A substrate and resulted in abnormally condensed chromatin. PTTG1-null cell proliferation was more sensitive to Aurora-A knock down and to Aurora kinase Inhibitor III treatment. The results indicate that PTTG1 and Aurora-A interact to regulate cellular responses to anti-neoplastic drugs. PTTG1 knockdown is therefore a potential approach to improve the efficacy of tumor Aurora kinase inhibitors.

Reference database for bone speed of sound measurement by a novel quantitative multi-site ultrasound device.

The nonuniform skeletal involvement in osteoporosis argues for multi-site evaluation. The Sunlight Omnisense (Sunlight Ultrasound Technologies, Israel) is a multi-site device that measures speed of sound (SOS) at the appendicular skeleton. We report the reference database for SOS at the radius (RAD), tibia (TIB), metatarsus (MTR) and phalanx (PLX). The database was obtained from 1521 healthy Israeli women (age 20-90 years) out of 2051 respondents. SOS was determined in 97.6% of the participants at the PLX, 96.4% at the TIB, 93.6% at the RAD and 85.1% at the MTR; it was not measurable in 0.5%. Short-term coefficient of variation was lowest at the RAD and always less than 1%. Maximal SOS was noted at 35-45 years of age in three of the sites (RAD 4169 m/s, MTR 3663 m/s, PLX 4047 m/s, respectively) but 10 years earlier at the TIB (3939 m/s). In the perimenopausal period (age 46-55 years), SOS was always lower in post- as compared with premenopausal women (p<0.05). Immediately following the menopause, SOS annually declined close to the short-term CV: 16, 34, 37 and 13 m/s at the RAD, PLX, MTR and TIB, respectively. The average age-stratified SOS values at various measurement sites were highly correlated at the population level (0.96-0.99), but less so at the individual level (0.40-0.57). Therefore, multi-site SOS measurements are better than single-site assessment. After 79 years of age, the average T-score at the RAD and PLX was <--2.5. This is similar to that of dual-energy X-ray absorptiometry (DXA)-determined spine bone mineral density (BMD) and somewhat lower than hip BMD. Equivalent T-score curves obtained by percentile adjustment of SOS at various sites to that of the RAD (at age group 60-69 years) reveal convergence and indicate that 52-68% of women older than 79 years are osteoporotic. In conclusion, multi-site peripheral SOS measurements reveal age-dependent bone changes with a high degree of measurement precision and indicate a prevalence of osteoporosis similar to that obtained by DXA.

Discrimination of proximal hip fracture by quantitative ultrasound measurement at the radius.

Osteoporosis is a disease that culminates in fragility fractures and, therefore, imposes major burden on the health economy. In dealing with this worldwide condition, it is prudent to use a reliable, inexpensive, portable diagnostic means that does not use ionizing radiation and is capable of measuring bone properties at several sites. Recently, a quantitative ultrasound device (Omnisense) that measures speed of sound (SOS) at multiple skeletal sites was introduced. The Omnisense combines the 'axial transmission' mode and the critical angle concept. Preliminary reports suggested that of the different skeletal sites measured by this device, the distal third of the radius is the preferred measurement site for osteoporosis. In this cross-sectional study, SOS was determined at the radius using Omnisense in 50 hip-fractured elderly women (group F, age 76.1 +/- 6.0 years), 130 elderly controls (group NF, age 71.5 +/- 5.2 years) and 185 young healthy controls (group YH, age 40.6 +/- 3.0 years). Actual SOS was significantly lower in group F compared with group NF (p = 0.0001). Whereas SOS T-scores calculated for each woman and stratified into age subgroups within each of the study groups indicate decline from -2.22 to -3.56 in group F and from -1.56 to -3.17 in group NF, there was an increase from -0.02 to 0.03 in group YH. Age- and BMI-adjusted logistic regression for hip fracture discrimination indicated an area under the receiver operating characteristic curve for hip fracture of 0.79 (95% CI, 0.73-0.86; p = 0.005) and an odds ratio of 1.92 (95% CI, 1.22-3.02; p = 0.005). We conclude that SOS measured at the radius by Omnisense discriminates subjects with hip fracture. from controls. Prospective studies are needed to support the role of Omnisense in assessing the risk of hip fracture.