bluuebunny/crossref_metadata_2025 huggingface dataset:
A Dega-type osteotomy after closure of the triradiate cartilage in non-walking patients with severe cerebral palsy
Authors: Robb J. E. , Brunner R.
Published: June 2006

A total of 47 non-walking patients (52 hips) with severe cerebral palsy and with a mean age of 14 years, (9 to 27) underwent a Dega-type pelvic osteotomy after closure of the triradiate cartilage, together with a derotation varus-shortening femoral osteotomy and soft-tissue correction for hip displacement which caused pain and/or difficulties in sitting. The mean follow-up was 48 months (12 to 153). The migration percentage improved from a pre-operative mean of 70% (26% to 100%) to 10% (0% to 100%) post-operatively. In five hips the post-operative migration percentage was greater than 25%, which was associated with continuing pain in two patients. Three patients had persistent hip pain and a migration percentage less than 25%. In five hips a fracture through the acetabulum occurred, and in another there was avascular necrosis of the superior acetabular segment, but these had no adverse effect on functional outcome. We conclude that it is possible to perform a satisfactory pelvic osteotomy of this type in these patients after the triradiate cartilage has been closed.
The Thompson hemiarthroplasty
Authors: Lloyd J. M. , Calder J. D. F.
Published: June 2006

The Thompson hemiarthroplasty is a popular hip prosthesis. We present two case reports highlighting a significant alteration in the design of the implant which compromised the success of the operations.

In recent years the manufacturing process of this prosthesis has changed, with a resultant increase in the volume of the stem of 10 ml.

It is essential that manufacturers inform orthopaedic surgeons of any alteration in the design of the implant and supply compatible instrumentation to minimise surgical errors. Surgeons must remain vigilant when checking the compatibility of the trial and definitive prostheses.
Combined anterior cruciate reconstruction and Oxford unicompartmental knee arthroplasty
Authors: Pandit H. , Beard D. J. , Jenkins C. , Kimstra Y. , Thomas N. P. , Dodd C. A. F. , Murray D. W.
Published: June 2006

The options for treatment of the young active patient with isolated symptomatic osteoarthritis of the medial compartment and pre-existing deficiency of the anterior cruciate ligament are limited. The potential longevity of the implant and levels of activity of the patient may preclude total knee replacement, and tibial osteotomy and unicompartmental knee arthroplasty are unreliable because of the ligamentous instability. Unicompartmental knee arthroplasties tend to fail because of wear or tibial loosening resulting from eccentric loading. Therefore, we combined reconstruction of the anterior cruciate ligament with unicompartmental arthroplasty of the knee in 15 patients (ACLR group), and matched them with 15 patients who had undergone Oxford unicompartmental knee arthroplasty with an intact anterior cruciate ligament (ACLI group). The clinical and radiological data at a minimum of 2.5 years were compared for both groups.

The groups were well matched for age, gender and length of follow-up and had no significant differences in their pre-operative scores. At the last follow-up, the mean outcome scores for both the ACLR and ACLI groups were high (Oxford knee scores of 46 (37 to 48) and 43 (38 to 46), respectively, objective Knee Society scores of 99 (95 to 100) and 94 (82 to 100), and functional Knee Society scores of 96 and 96 (both 85 to 100). One patient in the ACLR group needed revision to a total knee replacement because of infection. No patient in either group had radiological evidence of component loosening. The radiological study showed no difference in the pattern of tibial loading between the groups.

The short-term clinical results of combined anterior cruciate ligament reconstruction and unicompartmental knee arthroplasty are excellent. The previous shortcomings of unicompartmental knee arthroplasty in the presence of deficiency of the anterior cruciate ligament appear to have been addressed with the combined procedure. This operation seems to be a viable treatment option for young active patients with symptomatic arthritis of the medial compartment, in whom the anterior cruciate ligament has been ruptured.
Tumor Necrosis Factor-α −308G>A Allelic Variant Modulates Iron Accumulation in Patients with Hereditary Hemochromatosis
Authors: Krayenbuehl Pierre-Alexandre , Maly Friedrich E , Hersberger Martin , Wiesli Peter , Himmelmann Andreas , Eid Karim , Greminger Peter , Vetter Wilhelm , Schulthess Georg
Published: June 2006

Background: In vitro and animal studies suggest that tumor necrosis factor α (TNF-α) modulates intestinal iron transport. We hypothesized that the effect of TNF-α might be particularly relevant if iron absorption is not effectively controlled by the HFE gene.

Methods: In patients with homozygous C282Y hemochromatosis, we investigated the influence of TNF-α −308G>A allelic variant on total body iron overload, determined in all patients by measuring iron removed during depletion therapy, and hepatic iron index and need for phlebotomy to prevent iron reaccumulation, measured in patient subgroups.

Results: Of 86 patients with hereditary hemochromatosis, 16 (19%) were heterozygous carriers and 1 (1%) was a homozygous carrier of the TNF-α promoter −308A allele. Mean (SD) total body iron overload was increased 2-fold in TNF-α −308A allele carriers [10.9 (7.6) g] compared with homozygous carriers of the G allele [5.6 (5.0) g, P <0.001]. Hepatic iron index differed markedly between TNF-α −308A allele carriers [5.6 (3.5) μmol/g/year] and homozygous G allele carriers [3.1 (2.2) μmol/g/year, P = 0.040, n = 30]. After iron depletion, the need for phlebotomy to prevent iron reaccumulation (maintenance therapy) was substantially higher in TNF-α −308A allele carriers than in homozygous G allele carriers (P = 0.014, n = 73). We used multiple regression analyses to exclude possible confounding effects of sex, age, family screening, body-mass index, and meat or alcohol intake.

Conclusion: TNF-α −308G>A allelic variant modulates iron accumulation in patients with hereditary (homozygous C282Y) hemochromatosis, but the effect of the TNF-α −308A allele on clinical manifestations of hemochromatosis was less accentuated than expected from the increased iron load associated with this allele.
Shared Material and Grammar: Toward A Dependency Grammar Theory of Non-Gapping Coordination for English and German
Authors: Osborne Timothy
Published: June 2006

The paper presents a dependency grammar theory of non-gapping coordination. The approach draws a distinction etween standard cases of coordination - called String Coordination - and gapping. Only small conjuncts are acknowledged. The core of the approach is expressed in terms of three constraints - the Contiguity Requirement (CR), the Parallelism Requirement (PR), and the Restriction on Shared Constituents (RSC) - that restrict which strings may be coordinated and in terms of the material that conjuncts may share. The claims made are valid for both English and German.
Neutron Damage in SiC Semiconductor Radiation Detectors in the GT-MHR
Authors: Blue TE , Lohan B , Khorsandi B , Miller DW
Published: June 2006

As a part of a U.S. Department of Energy Nuclear Engineering Research Initiative (NERI) project, we are evaluating the potential for using silicon carbide (SiC) semiconductor radiation detectors, operating in the pulse mode, as power monitors for gas turbine modular helium reactor (GT-MHR) [1]. Locations for the power monitors will be selected considering acceptable detector count rates and lifetimes. We have characterized the radiation environment at various locations in the GT-MHR, where detectors may be placed, in terms of the 1 MeV equivalent neutron flux in SiC (φeq,1 MeV, SiCTotal). Also, we have characterized the radiation field in beam part 1 (BP1) of the Ohio State University Research Reactor (OSURR) in these same terms, with the intent of correlating observed degradation of the SiC detectors in the OSURR to the degradation that can be expected for various detector locations in the GT-MHR. Comparing φeq,1 MeV, SiCTotal for the GT-MHR and for the OSURR, we conclude that SiC devices cannot be adequately tested in the characterization vessel in OSURR BP1 for the radiation damage that would be incurred over a refueling cycle for detectors placed in-core. Also, we note that the radiation environment in the OSURR BP1 is harder than the radiation environment in the GT-MHR.
Round Robin Test on Normalization Method under Static Loading Condition
Authors: Oh YJ , Hwang IS , Joyce JA
Published: June 2006

In 2001, the normalization method was approved as ASTM Method E 1820-01 [1] for use in high loading rate J-R tests. Prior to its approval, High Rate Round Robin was conducted under the coordination of ASTM Subcommittee E08.08.02 for the verification of accuracy and reproducibility of the method. However, the results of the normalization method cannot be verified against those of other well-established methods because no other method is available in the high loading rate condition. In this round robin test, J-R curves were measured under static loading conditions for A106Gr. C nuclear piping steel by the normalization method so that results can be compared with those obtained simultaneously by the unloading compliance method. The deviation of JIc by normalization and differences of JIc values from those of the unloading compliance method were quantified. The normalization method showed JIc deviation up to 60 % when tested with initial a/W=0.5. In order to seek ways to reduce the deviation, both offset method and tangent method were tried for normalization analysis, but with limited improvement. These partially modified normalization methods of the offset method and tangent method decreases the deviation of JIc, but increases the difference from those of the unloading compliance method. More fundamental approaches are warranted for adequate improvement.
Expression of adrenomedullin in adipose tissue of lean and obese women
Authors: Paulmyer-Lacroix O , Desbriere R , Poggi M , Achard V , Alessi M-C , Boudouresque F , Ouafik L’H , Vuaroqueaux V , Labuhn M , Dutourand A , Grino M
Published: June 2006

Objective: Adrenomedullin (AM), a potent vasodilatator and antioxidative peptide, was shown recently to be expressed by adipose tissue. The aim of our study was to investigate the precise localization of AM within human adipose tissue, and to examine AM regulation in obesity.

Design: Subcutaneous (SC) and omental (OM) adipose tissues from 9 lean and 13 obese women were profiled for AM expression changes. Preadipocytes from human adipose tissue were isolated and differentiated under defined adipogenic conditions.

Methods: AM expression was analyzed by immunohistochemistry, in situ hybridization and quantitative RT-PCR.

Results: A strong AM expression was observed in vessel walls, stromal cell clusters and isolated stromal cells, some of them being CD 68 positive, whereas mature adipocytes were not labeled. Calcitonin receptor-like receptor and receptor activity-modifying proteins (RAMP) 2 and RAMP 3 were expressed in vessel walls. In vitro, preadipocytes of early differentiation stages spontaneously secreted AM. No difference in AM localization was found between SC and OM adipose tissue. AM levels in SC tissue did not differ between lean and obese subjects. By contrast, AM levels in OM tissue were significantly higher in obese as compared with lean women. Moreover, we found a positive relationship between OM AM and tumor necrosis factor α mRNA levels and AM-immunoreactive area in OM tissue followed the features of the metabolic syndrome.

Conclusion: Stromal cells from human adipose tissue, including macrophages, produce AM. Its synthesis increased in the OM territory during obesity and paralleled the features of the metabolic syndrome. Therefore, AM should be considered as a new member of the adipokine family.
Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy
Authors: Lee Dae-Yeol , Kim Sun-Young , Jo Dae-Sun , Hwang Pyoung Han , Kang Kyung Pyo , Lee Sik , Kim Won , Park Sung Kwang
Published: June 2006

Objective: Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy.

Design: The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction.

Methods: Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure.

Results: The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P<0.01) than in patients with normal renal function (42.0%) or in the diabetes control group (40.6%). The Leu72Met polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P<0.05).

Conclusion: These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.
Clinical and biochemical description of a novel CYP21A2 gene mutation 962_963insA using a new 3D model for the P450c21 protein
Authors: Janner Marco , Pandey Amit V , Mullis Primus E , Flück Christa E
Published: June 2006

Objective: A severely virilized 46, XX newborn girl was referred to our center for evaluation and treatment of congenital adrenal hyperplasia (CAH) because of highly elevated 17α-hydroxyprogesterone levels at newborn screening; biochemical tests confirmed the diagnosis of salt-wasting CAH. Genetic analysis revealed that the girl was compound heterozygote for a previously reported Q318X mutation in exon 8 and a novel insertion of an adenine between nucleotides 962 and 963 in exon 4 of the CYP21A2 gene. This 962_963insA mutation created a frameshift leading to a stop codon at amino acid 161 of the P450c21 protein.

Aim and methods: To better understand structure–function relationships of mutant P450c21 proteins, we performed multiple sequence alignments of P450c21 with three mammalian P450s (P450 2C8, 2C9 and 2B4) with known structures as well as with human P450c17. Comparative molecular modeling of human P450c21 was then performed by MODELLER using the X-ray crystal structure of rabbit P450 2B4 as a template.

Results: The new three dimensional model of human P450c21 and the sequence alignment were found to be helpful in predicting the role of various amino acids in P450c21, especially those involved in heme binding and interaction with P450 oxidoreductase, the obligate electron donor.

Conclusion: Our model will help in analyzing the genotype–phenotype relationship of P450c21 mutations which have not been tested for their functional activity in an in vitro assay.
Early textural and functional alterations of left ventricular myocardium in mild hypothyroidism
Authors: Fabrizio Aghini-Lombardi , Vitantonio Di Bello , Enrica Talini , Andrea Di Cori , Fabio Monzani , Lucia Antonangeli , Caterina Palagi , Nadia Caraccio , Grazia Delle Donne Maria , Carmela Nardi , Angela Dardano , Alberto Balbarini , Mario Mariani , Aldo Pinchera
Published: June 2006

The aim of the present study was to evaluate cardiac function and texture in patients with subclinical hypothyroidism (sHT) both by conventional and new ultrasonic intramyocardial tissue techniques. sHT was characterized by normal serum free tetraiodotironine and free triiodotironine levels and slightly increased serum TSH level. Twenty-four patients affected by sHT and 24 sex- and age-matched healthy volunteers were studied. All subjects were submitted to conventional two-dimensional (2D)-color Doppler echocardiography, pulsed wave tissue Doppler imaging (PWTDI) for the analysis of the diastolic function, color Doppler myocardial imaging (CDMI) for the analysis of regional strain and strain-rate and integrated backscatter (IBS) for the evaluation of intrinsic contractility and tissue characterization. The results of the present study were: (a) the detection in sHT subjects of a lower cyclic variation index (CVI) indicating an altered myocardial intrinsic contractility; (b) a higher ultrasonic myocardial reflectivity indicating an altered myocardial texture; (c) the detection of lower systolic strain and strain-rate indicating an alteration of myocardial regional deformability; (d) an initial impairment of left ventricular diastolic function indicated by a decrease of peak E mitral flow velocity and an increase of peak A mitral flow velocity. All parameters studied with conventional 2D-echo in sHT patients were comparable with controls, except for a mild alteration in diastolic function. A significant correlation among systo-diastolic modifications detected by CDMI and IBS and serum TSH levels were found. The CVI at septum, the PWDTI S-peak wave and the systolic strain at septum were inversely related to the serum TSH levels. In conclusion, the new intramyocardial ultrasonic techniques confirm and extend the previous knowledge on the effect of the sHT on the heart, allowing the detection of early ultrastructural and regional functional systolic and diastolic abnormalities.
Does long-term GH replacement therapy in hypopituitary adults with GH deficiency normalise quality of life?
Authors: Koltowska-Häggström Maria , Mattsson Anders F , Monson John P , Kind Paul , Badia Xavier , Casanueva Felipe F , Busschbach Jan , Koppeschaar Hans P F , Johannsson Gudmundur
Published: June 2006

Objective: To determine whether impaired quality of life (QoL) in adults with GH deficiency (GHD) is reversible with long-term GH therapy and whether the responses in QoL dimensions differ from each other.

Methods: QoL was measured by the Quality of Life–Assessment for Growth Hormone Deficiency in Adults (QoL-AGHDA) in general population samples in England & Wales, The Netherlands, Spain and Sweden (n = 892, 1038, 868 and 1682 respectively) and compared with corresponding patients’ data from KIMS (Pfizer International Metabolic Database) (n = 758, 247, 197 and 484 respectively) for 4–6 years a follow-up. The subsets of patients from England and Wales, and Sweden with longitudinal data for 5 years’ follow-up were also analysed. The change of the total QoL-AGHDA scores and responses within dimensions were evaluated. Subanalyses were performed to identify any specificity in response pattern for gender, age, disease-onset and aetiology.

Results: Irrespective of the degree of impairment, overall QoL improved dramatically in the first 12 months, with steady progress thereafter towards the country-specific population mean. Problems with memory and tiredness were the most serious burden for untreated patients, followed by tenseness, self-confidence and problems with socialising. With treatment, these improved in the reverse order, normalising for the latter three.

Conclusions: Long-term GH replacement results in sustained improvements towards the normative country-specific values in overall QoL and in most impaired dimensions. The lasting improvement and almost identical pattern of response in each patient subgroup and independent of the level of QoL impairment support the hypothesis that GHD may cause these patients’ psychological problems.
Thyroid nodule shape suggests malignancy
Authors: Cappelli Carlo , Castellano Maurizio , Pirola Ilenia , Gandossi Elena , De Martino Elvira , Cumetti Davide , Agosti Barbara , Rosei Enrico Agabiti
Published: June 2006

Objective: To evaluate if a nodule with shape taller than wide (anteroposterior/transverse diameter ratio, A/T≥ 1) is a good predictor of malignancy independent of the size.

Methods: We retrospectively examined the cytological and histological results of 7455 nodules (5198 patients) referred for ultrasound-guided-fine needle aspiration cytology (US-FNAC) in our hospital from January 1991 to September 2004.

Results: A suitable FNAC was obtained from 6135 nodules (4495 patients); 34.6% were less than 1 cm in diameter (small nodules, SN). A diagnosis of carcinoma was histologically confirmed in 284/349 suspicious lesions after FNAC. The size of carcinoma nodules was not significantly associated with the occurrence of extracapsular growth (large nodules (LN): 10.5%, SN: 4.9%, NS) and lymph node metastasis (LN: 23.6%, SN: 25.0%, NS). Malignant lesions showed microcalcifications more frequently than benign nodules (72.2 vs 28.7%; P < 0.001; (odds ratio, OR(confidence intervals, CI) = 9.9(7.2–13.4)). Similarly, A/T≥ 1 (76 vs 40%; P < 0.001; OR(CI) = 8.6(5.5–13.1)), blurred margins (52.8 vs 18.8%; P < 0.001; OR(CI) = 7.7(5.6–10.2)), solid hypo-echoic appearance (80.6 vs 52.4%; P < 0.001; OR(CI) = 3.2(2.2–4.3)) and intranodular vascular pattern (type 2) (61.6 vs 49.7%; P < 0.001; OR(CI) = 1.7(1.3–2.3)) were significantly more frequent in malignant than in benign nodules.

Conclusions: Our data show that no single parameter, including nodule size, satisfactorily identifies a subset of patients to be electively investigated by FNAC. We concluded that A/T≥ 1 with at least two of US features (microcalcification, blurred margins, hypo-echoic pattern) is today the best compromise between missing cancers and cost–benefit.
Serum leptin and C-reactive protein levels in the physiological spontaneous menstrual cycle in reproductive age women
Authors: Wunder D M , Yared M , Bersinger N A , Widmer D , Kretschmer R , Birkhäuser M H
Published: June 2006

Objective: Only a few studies have investigated variations of different markers for inflammatory processes during the physiological menstrual cycle. The results are conflicting, particularly concerning the correlation between the marker leptin and steroid hormones. The aim of the study was to investigate the inflammatory markers C-reactive protein (CRP) and leptin in the serum of healthy, normally ovulating women and to correlate these with each other and with the hormones of the gonadal axis. A cycle-dependence of the markers studied would imply an exact timing of the blood sampling for clinical needs.

Design: Observational study investigating the two inflammatory markers CRP and leptin in relation to the hormonal pattern of the gonadal axis during the normal cycle.

Methods: Ovulatory cycles of 36 healthy, young, normo-androgenic women, having a normal body mass index were evaluated. Serum concentrations of leptin and CRP, as well as of follicle-stimulating hormone, luteinising hormone, 17β-oestradiol, progesterone, prolactin (PRL) and free testosterone were measured every 1–2 days during one full cycle.

Results: Serum levels of leptin and CRP behaved differently during ovulatory cycles, with higher concentrations for leptin only during certain phases. Significant correlations were found in the follicular phase between leptin and PRL and leptin and free testosterone.

Conclusions: Leptin levels change during the menstrual cycle. Leptin levels are more stable on cycle days 1–5 than later in the cycle. For precise cycle-independent measurements, these fluctuations have to be taken into account. There is no similar cyclic pattern for CRP.
Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults – a KIMS database analysis
Authors: Abs Roger , Feldt-Rasmussen Ulla , Mattsson Anders F , Monson John P , Bengtsson Bengt-Åke , Góth Miklós I , Wilton Patrick , Koltowska-Häggström Maria
Published: June 2006

Objective: The aim of the present study was to clarify the relationship between GH deficiency (GHD) and some cardiovascular risk factors and to analyse the effect of GH replacement therapy in a large number of patients over a prolonged period of time.

Design: Data for analysis were retrieved from KIMS (Pfizer International Metabolic Database). Serum concentrations of total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides were obtained from 2589 patients at baseline and from 1206 patients after 1 and 2 years of GH replacement therapy. Body mass index (BMI), waist and hip, resting blood pressure and body composition were also measured.

Results: At baseline, the unfavourable effects of GHD were most obvious in the lipid profile demonstrating elevated mean total and LDL-cholesterol, in the increased waist circumference and the elevated BMI. The cholesterol concentration, BMI and body composition were significantly adversely affected by a number of factors, including age, sex and the use of anti-epileptic drugs. The therapeutic effect of GH was essentially uniform across the whole population. GH replacement reduced significantly the mean total and LDL-cholesterol, the waist circumference and the fat mass and was maintained during 2 years.

Conclusions: This analysis of a large number of patients confirmed that GHD adults present with an increased cardiovascular risk. The sustained improvement of the adverse lipid profile and body composition suggests that GH replacement therapy may reduce the risk of cardiovascular disease and the premature mortality seen in hypopituitary patients with untreated GHD.
The spectrum of parathyroid gland dysfunction associated with the microdeletion 22q11
Authors: Hiéronimus Sylvie , Bec-Roche Magali , Pedeutour Florence , Lambert Jean Claude , Wagner-Malher Kathy , Mas Jean Christophe , Sadoul Jean Louis , Fénichel Patrick
Published: June 2006

Objective: Clinical features associated with microdeletion of chromosome 22q11 (del(22)(q11)) are highly variable. Increased awareness of this condition is needed among specialists such as endocrinologists to reduce diagnostic delay and improve clinical care. The purpose of this study was to describe the phenotype of patients with del(22)(q11), focusing on parathyroid gland dysfunction.

Design and methods: Charts of 19 patients, including one kindred of three, known to have del(22)(q11) diagnosed by fluorescence in situ hybridization (FISH) were reviewed from the register of the department of Medical Genetics. Major clinical features including hypoparathyroidism phenotype were collected.

Results: Parathyroid dysfunction was present in 8 out of 16 patients (50%). Six patients were diagnosed with overt hypoparathyroidism. Hypocalcemia manifested as laryngeal stridor within the first days of life (n=3), seizures in infancy (n=1) and adolescence (n=2). The connection between hypoparathyroidism and diagnosis of del(22)(q11) was belated at the median age of 18 years. One patient had presented with transient neonatal hypoparathyroidism, and one patient had latent hypoparathyroidism. Within the kindred family, the phenotype variability including that of parathyroid dysfunction was as marked as between unrelated individuals. Standard karyotype failed to detect the deletion in 15 out of 19 cases.

Conclusions: Abnormal parathyroid function in the del(22)(q11) ranges from severe neonatal hypocalcemia to latent hypoparathyroidism. Del(22)(q11) should be considered as a potential cause of hypocalcemia even in young adult. When suspected, the diagnosis requires investigation by FISH. Furthermore, long-term calcemia follow-up is needed in normocalcemic patients with del(22)(q11) because of the possible evolution to hypocalcemic hypoparathyroidism.
The reduction of bone mineral density in postmenopausal women with primary hyperparathyroidism is higher in the presence of concomitant GH secretion impairment
Authors: Cecconi Elisabetta , Gasperi Maurizio , Genovesi Maura , Bogazzi Fausto , Grasso Lucia , Cetani Filomena , Procopio Massimo , Marcocci Claudio , Bartalena Luigi , Martino Enio
Published: June 2006

Objective: To investigate, in a large group of postmenopausal primary hyperparathyroidism (PHP) women, whether the concomitance of GH deficiency (GHD) may contribute to the development of changes in bone mineral density (BMD).

Design: GH secretion, bone status and metabolism were investigated in 50 postmenopausal women with PHP and in a control group of 60 women with no evidence of PHP, matched for age, age at menopause and body mass index (BMI).

Methods: GH response to growth hormone-releasing hormone (GHRH)+arginine (Arg), femoral neck BMD (g/cm2) by dual energy X-ray absorptiometry, BMI, serum-ionized calcium, parathyroid hormone (PTH) and markers of bone remodelling were evaluated in all patients and controls.

Results: Among PHP patients, GH secretion was reduced (8.8 ± 4.2 μg/l, range 1.1–16.5 μg/l) in 34 patients and normal (28.7 ± 11.8 μg/l, range 17.9–55.7 μg/l) in the remaining 16 (P < 0.05), no women in the control group had GHD (peak GH 33.8 ± 10.9 μg/l, range 21.7 ± 63.2 μg/l). Osteoporosis (T-score < − 2.5) and osteopenia (T-score > −2.5 and < −1) were found in 73.5 and 17.6% of GHD patients, in 37.5 and 43.7% of patients with normal GH secretion and 3.1 and 27% of controls. T-score and BMD were not correlated with ionized calcium, age, age at menopause, BMI, GH peak and IGF-I but were correlated with serum PTH levels in both groups. T-score was correlated with serum levels of markers of bone remodelling only in PHP patients with GHD.

Conclusions: Concomitant impairment of GH secretion may play a pathogenetic role in the occurrence of changes in bone mass observed in PHP and contribute to make them more severe.
GH secretory pattern in young adults who discontinued GH treatment for GH deficiency and decreased longitudinal growth in childhood
Authors: Svensson Johan , Johannsson Gudmundur , Iranmanesh Ali , Albertsson-Wikland Kerstin , Veldhuis Johannes D , Bengtsson Bengt-Åke
Published: June 2006

Objective: Some adolescents who discontinue GH treatment due to GH deficiency (GHD) and short stature in childhood do not have classical GHD at retesting in adult life. It is unknown whether there is a neuroendocrine disturbance in the spontaneous pattern of GH release in these patients.

Design/patients/methods: Thirty-seven adolescents, who had received treatment with GH due to impaired longitudinal growth, were included. The adolescents were divided into two groups; one (GHD; n = 19) with classical GHD in adult life and another (GH sufficient (GHS); n = 18) without classical adult GHD. One year after GH discontinuation, 24-h GH profiles were performed with blood sampling every 30 min. Sixteen matched healthy controls were also studied. All blood samples were analysed using an ultrasensitive GH assay and then, approximate entropy (ApEn) and deconvolution analysis were performed.

Results: The GHD group had higher mean ApEn level than the healthy controls (P < 0.05). As measured by deconvolution analysis, they had lower basal GH secretion (P < 0.01), increased number of GH peaks (P < 0.001), but lower burst mass (P < 0.001), lower percentage pulsatile GH secretion (P < 0.001) and lower total GH secretion (P < 0.001), compared with control subjects. Adolescents in the GHS group had a pattern of 24-h GH release similar to that in healthy controls.

Conclusion: Young adults with childhood-onset severe GHD have a high-frequency, low-amplitude GH secretion with decreased orderliness. The adolescents without classical GHD in adult life maintain a pattern of spontaneous GH release that is not statistically different from that in the healthy controls.
Primary hypophysitis: clinical-pathological correlations
Authors: Gutenberg Angelika , Hans Volkmar , Puchner Maximilian J A , Kreutzer Jürgen , Brück Wolfgang , Caturegli Patrizio , Buchfelder Michael
Published: June 2006

Objective: Primary hypophysitis comprises of three distinct histomorphological entities: lymphocytic, granulomatous and xanthomatous. Clinical features of the three subtypes for diagnostic and treatment strategies have yet not been well characterized.

Methods: Endocrine function, visual fields and acuity as well as magnetic resonance imaging characteristics were assessed before and after transphenoidal surgery in the largest series of 31 patients with primary hypophysitis (21 lymphocytic, 6 granulomatous, and 4 xanthomatous cases).

Results: Only lymphocytic hypophysitis occurred during pregnancy (30%) and was associated with other autoimmune diseases (24%). Visual fields and acuity abnormalities were not seen in xanthomatous hypophysitis. Lymphocytic and granulomatous hypophysitis most often resulted in severe dysfunction of the adrenal, gonadal and thyroidal axes as well as diabetes insipidus. For patients presenting with xanthomatous hypophysitis most often, mild anterior pituitary axis failure was documented and posterior pituitary involvement was hardly found. The outcome after transphenoidal biopsy was generally favorable. Pre- or postsurgical glucocorticoid treatment was very effective in 75% of the lymphocytic form in reducing the pituitary size. In contrast, glucocorticoid therapy was less effective in granulomatous or xanthomatous hypophysitis.

Conclusion: Diffuse destruction of the complete pituitary gland including the infundibulum has to be considered in lymphocytic and granulomatous hypophysitis, whereas in xanthomatous, a circumscribed anterior pituitary lesion leading to compression of the pituitary gland without alteration of the pituitary stalk and optic chiasm can be assumed.
Phenotypic variation in constitutional delay of growth and puberty: relationship to specific leptin and leptin receptor gene polymorphisms
Authors: Banerjee Indraneel , Trueman Julie A , Hall Catherine M , Price David A , Patel Leena , Whatmore Andrew J , Hirschhorn Joel N , Read Andrew P , Palmert Mark R , Clayton Peter E
Published: June 2006

Objectives: Constitutional delay of growth and puberty (CDGP) is a variant of normal pubertal timing and progress, often with dominant inheritance. It is likely that one or more genes will be associated with CDGP. Possible candidates are the leptin (L) and the leptin receptor (LR) genes, as the leptin axis links nutritional status to pubertal development. This study has assessed whether a) L or LR gene polymorphisms were associated with CDGP and b) the CDGP phenotype was influenced by these polymorphisms.

Design: Case–control and transmission disequilibrium tests were used to test genetic association of L and LR polymorphisms with CDGP.

Methods: We genotyped L (3′CTTT repeat) and LR polymorphisms (Gln>Arg substitution, exon 6) in 81 CDGP children and 94 controls in the UK and 88 CDGP children from the US and assessed the effect of genotype on their anthropometric characteristics.

Results: There was no association of these L or LR gene polymorphisms with CDGP. There was no difference in height or bone age delay within L or LR genotypes. However, UK CDGP children homozygous for the L short allele were heavier than heterozygotes and long allele homozygotes, with a similar trend in the US cohort. UK CDGP children with severe pubertal delay, who were thin, had significantly greater bone age delay and an increased frequency of parental pubertal delay than other groups and were less likely to be L short allele homozygotes.

Conclusions: There was no association of specific L or LR polymorphisms with CDGP, but L short allele carriage influenced the phenotype within CDGP.
Oxidised low-density lipoprotein concentration – early marker of an altered lipid metabolism in young women with PCOS
Authors: Macut Djuro , Damjanović Svetozar , Panidis Dimitrios , Spanos Nikolaos , Glišić Biljana , Petakov Milan , Rousso David , Kourtis Anargyros , Bjekić Jelica , Milić Nataša
Published: June 2006

Objective: Women with polycystic ovary syndrome (PCOS) are assumed to be at increased risk for cardiovascular diseases. This study examined the variations in oxidised low-density lipoprotein (OxLDL) concentration in relation to insulin levels in young women with PCOS.

Design: Cross-sectional clinical study in tertiary cares research hospitals. A total of 179 women with PCOS (79 overweight) and 56 age- and body mass index-matched controls were examined.

Methods: Blood samples were collected in follicular phase of the cycle for the basal glucose, total-, high-density lipoprotein-cholesterol (HDL-C) and LDL-cholesterol, OxLDL, triglycerides, apolipoprotein–A1 (Apo-A1) and B (Apo-B), lipoprotein (a), insulin, testosterone and sex hormone-binding globulin (SHBG). Homeostatic model index (HOMA) and free androgen index (FAI) were determined.

Results: Overweight and normal weight women with PCOS had higher concentrations of OxLDL than their control counterparts (P=0.007 and 0.003 respectively). Both the basal insulin (P=0.003) and HOMA values (P<0.001) were significantly higher in overweight than normal weight patients. Testosterone and FAI were higher in patients than in the respective controls (P<0.001). The only independent predictor of increased OxLDL concentration in normal weight patients was Apo-B-to-Apo-A1 ratio (P<0.001, odds ratio (OR) 6.1; 95% confidence interval (CI) 2.3–16.4), while in obese PCOS, it was total cholesterol-to-high-density lipoprotein cholesterol ratio (P<0.001, OR 2.8; 95% CI 1.6–4.9).

Conclusion: Young normal weight and overweight PCOS women have similarly increased OxLDL levels. Our results may indicate the presence of primary alteration in lipid metabolism in patients with PCOS. To answer the question whether the alteration in LDL particle size can by itself pose a higher cardiovascular risk, a careful follow-up of these women is needed.
A gene-to-gene interaction between aromatase and estrogen receptors influences bone mineral density
Authors: Riancho José A , Zarrabeitia María T , Valero Carmen , Sañudo Carolina , Mijares Verónica , González-Macías Jesús
Published: June 2006

Objective: The aromatization of androgenic precursors is the main source of estrogens in postmenopausal women. We tested the hypothesis that allelic variants of the genes coding for aromatase and estrogen receptors (ER) could interact to determine the estrogenic signals on the bone tissue and, consequently, bone mineral density (BMD).

Design: Cross-sectional study including 331 postmenopausal women.

Methods: BMD was measured by dual energy x-ray absorptiometry. A CG polymorphism of the aromatase gene as well as three polymorphisms of ERα (a TA repeat in the promoter region, a C T single nucleotide polymorphism (SNP) in intron 1 and an AG SNP in exon 8) and a CA repeat polymorphism of ERβ were studied.

Results: Age, body weight and the aromatase genotype were associated with BMD. Allelic variants of ERβ and the exon 8 of ERα did not show a significant association with BMD. The polymorphisms located on the promoter and intron 1 of ERα interacted strongly with aromatase. Thus, in women TT homozygous for the ERα gene, there was a marked influence of aromatase genotypes on BMD: spine BMD was 0.724±0.027 g/cm2 in women with CC aromatase alleles and 0.926±0.032 g/cm2 in those with GG alleles (P<0.001). Hip BMD in women with CC and GG aromatase genotypes was 0.722±0.020 and 0.842±0.026 g/cm2 respectively (P=0.002). On the contrary, there were no aromatase-related differences in BMD in women with CT/CC alleles of ERα. Similarly, aromatase-related differences in BMD were found in women with short alleles at the promoter region of ERα, but not in those with long alleles. Both ERα polymorphisms were in strong linkage disequilibrium (P<0.001).

Conclusion: These results suggest that the interaction between polymorphisms of genes involved in estrogen synthesis and estrogen signaling exerts an important influence on BMD in postmenopausal women, thus helping to explain, in part, its heritable component. Nevertheless, further studies are warranted to confirm this gene-to-gene interaction in other populations.
Perchlorate versus other environmental sodium/iodide symporter inhibitors: potential thyroid-related health effects
Authors: De Groef Bert , Decallonne Brigitte R , Van der Geyten Serge , Darras Veerle M , Bouillon Roger
Published: June 2006

Objective: Perchlorate is a known competitive inhibitor of the sodium/iodide symporter (NIS). Possible thyroid-related effects of environmental perchlorate have created great health concerns, especially in the US, resulting in a debated reference dose (RfD) of 0.0007 mg/kg per day in drinking water recommended by the National Academy of Sciences (NAS). However, the impact of other environmental NIS inhibitors and the role of iodine seem to have received little attention in the whole debate.

Methods: We performed a PubMed search for articles published up to February 2006, using the key terms perchlorate, nitrate, thiocyanate, iodine, NIS, RfD, thyroid (alone or in combinations), with particular attention for human studies. In parallel, we critically analysed the January 2005 NAS’ report, entitled ‘Health implications of perchlorate ingestion’.

Results: The relative potencies of prevalent environmental NIS inhibitors (nitrate, thiocyanate and perchlorate) to inhibit iodine uptake have been estimated repeatedly with robust results. Our calculations show that nitrate and thiocyanate, acquired through drinking water or food, account for a much larger proportion of iodine uptake inhibition than perchlorate. Furthermore, the iodine uptake inhibitory effects of nitrate and thiocyanate – as defined by their legally accepted maximal contaminant levels in drinking water – exceed the potential effect of the proposed RfD for perchlorate by far.

Conclusions: Iodine uptake inhibition and any potential downstream effect by perchlorate are highly dependent on the presence of other environmental NIS inhibitors and iodine intake itself. These potential confounders should therefore be considered in future studies and calculations for risk assessment.
Incidence of GH deficiency – a nationwide study
Authors: Stochholm Kirstine , Gravholt Claus H , Laursen Torben , Jørgensen Jens O , Laurberg Peter , Andersen Marianne , Kristensen Lars Ø , Feldt-Rasmussen Ulla , Christiansen Jens S , Frydenberg Morten , Green Anders
Published: June 2006

Objective: Data on incidence rates are scarce in GH deficiency (GHD). Here, we estimate the incidence rate in childhood onset (CO) and adult onset (AO) GHD in Denmark.

Design: We used three national registries to identify 9131 cases with an increased risk of GHD. Date of entry was defined using the date when a registration had taken place and when a date of sufficient information could be defined from a thorough examination of a record of a GHD patient, which ever came last. We considered date of entry as the incident date.

Methods: Sex-specific incidence rates of GHD in children and adults using the background population as reference.

Results: During 1980–1999, 1823 patients were incident. Three-hundred and three males and 191 females had CO, 744 males and 585 females had AO GHD. The incidence rate over time was stable for females with AO GHD and increasing for the other three subgroups. Average incidence rate for CO males, 2.58 (95% confidence interval (CI), 2.30–2.88), CO females, 1.70 (95% CI, 1.48–1.96), AO males, 1.90 (95% CI, 1.77–2.04), and AO females, 1.42 (95% CI, 1.31–1.54) all per 100 000. The incidence rate was significantly higher in males compared to females in the CO GHD group (P < 0.001) and in the AO GHD group in the age ranges of 45–64 and 65+years (P < 0.001). There was no significant difference in the 18–44 years age group.

Conclusions: In conclusion, we have identified the incidence rates of GHD in a nationwide study of Denmark. In this population-based study, we have identified in CO GHD and in the two oldest age groups of AO GHD, a statistically significant higher incidence rate in males when compared with females.
Hypothalamic–pituitary–adrenal axis activity in adults who were prenatally exposed to the Dutch famine
Authors: de Rooij Susanne R , Painter Rebecca C , Phillips David I W , Osmond Clive , Michels Robert P J , Bossuyt Patrick M M , Bleker Otto P , Roseboom Tessa J
Published: June 2006

Objective: The hypothalamic–pituitary–adrenal (HPA) axis has been proposed to be susceptible to fetal programming, the process by which an adverse fetal environment elicits permanent physiological and metabolic alterations predisposing to disease in later life. It is hypothesized that fetal exposure to poor circumstances alters the set point of the HPA axis, leading to increased HPA axis activity and subsequent increased cortisol concentrations. In this study, we tested the hypothesis that prenatal exposure to famine during different periods of gestation is associated with increased activity of the HPA axis.

Design and methods: We assessed plasma cortisol concentrations after a dexamethasone suppression and an ACTH1–24-stimulation test in a group of 98 men and women randomly sampled from the Dutch famine birth cohort. Cohort members were born as term singletons around the 1944–1945 Dutch famine.

Results: Cortisol profiles after dexamethasone suppression and ACTH1–24 stimulation were similar for participants exposed to famine during late, mid- or early gestation (P=0.78). Cortisol concentrations after dexamethasone suppression test did not differ between those exposed and those unexposed to famine in utero (mean difference −2% (95% confidence interval (CI) −27 to 23)). Neither peak cortisol concentration (20 nmol/l (95% CI −27 to 66)), cortisol increment (−5 nmol/l (95% CI −56 to 47)) or cortisol area under the curve post-ACTH1–24 injection (4% (95% CI −4 to 12)) differed between exposed and unexposed participants.

Conclusions: Prenatal famine exposure does not seem to affect HPA axis activity at adult age, at least not at the adrenal level. This does not exclude altered HPA axis activity at the levels of the hippocampus and hypothalamus.
Increased adiponectin receptor-1 expression in adipose tissue of impaired glucose-tolerant obese subjects during weight loss
Authors: Kim M J , Maachi M , Debard C , Loizon E , Clément K , Bruckert E , Hainque B , Capeau J , Vidal H , Bastard J P
Published: June 2006

Objective: To investigate the mRNA expression of adiponectin, AdipoR1 and AdipoR2, the two recently cloned adiponectin receptors and peroxisome proliferator activated receptor (PPAR)γ2 in adipose tissue of obese individuals before and during a very low calorie diet (VLCD) inducing weight loss.

Methods: Twenty-three non-diabetic obese subjects with normal (NGT, n=11) or impaired glucose tolerance (IGT, n=12) (age, 47±3 years; body mass index, 39.3±1.3 kg/m2) were studied before and after a 3-week 3.9 MJ diet daily without exercise. mRNA levels of nine IGT and six NGT subjects were measured by real-time PCR in s.c. abdominal adipose tissue.

Results: Metabolic parameters and insulin sensitivity were improved by VLCD in the IGT group, but minimally affected in the NGT group. VLCD increased expression of AdipoR1 in the IGT (P=0.02), but not in the NGT group. Adiponectin, AdipoR2 and PPARγ2 mRNA levels did not change during VLCD in any group. In the IGT, but not in the NGT group, AdipoR1 and AdipoR2 expressions were positively related to that of PPARγ2 and, after VLCD, AdipoR1 and AdipoR2 expressions were positively related to each other and to that of adiponectin.

Conclusion: In the NGT group, the 3-week VLCD inducing weight loss did not modify metabolic parameters, insulin sensitivity and the expression of the adiponectin system in adipose tissue. By contrast, in the IGT group, AdipoR1 expression increased and we found a coordinate regulation of the expression of adiponectin and its receptors. These modifications could participate, through adiponectin action on adipocytes, to the improved metabolic parameters observed in IGT subjects.