bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-dose glucose infusion after achieving critical hypoglycemia during insulin tolerance testing: effects on time of hypoglycemia, neuroendocrine stress response and patient’s discomfort in a pilot study
Authors: Borm K , Slawik M , Beuschlein F , Seiler L , Flohr F , Berg A , Koenig A , Reincke M 
Published: September 2005

Objective: The insulin tolerance test (ITT) is regarded as the gold standard for the evaluation of pituitary ACTH and growth hormone reserve. However, the intended critical hypoglycemia results in considerable discomfort and requires close surveillance during the test.
Design and methods: In a pilot study, we evaluated whether the ITT could be markedly simplified, made less hazardous and more convenient by routine i.v. low-dose glucose administration after hypoglycemia has been achieved. Sixteen healthy subjects (three females, 13 males) were tested twice in a randomized, single-blinded fashion, receiving 0.15 IU insulin/kg body weight as an i.v. bolus. After hypoglycemia (serum glucose less than 2.2 mmol/l) had been achieved, 500 ml isotonic saline (protocol A (A)), or 500 ml 5% glucose solution (protocol B (B)) were infused over 30 min.
Results: Compared with saline, glucose infusion shortened the period of hypoglycemia from 31 + 14 to 17 + 6 min (P < 0.01). In addition, prolonged duration of hypoglycemia (>45 min) was reduced (6 subjects in protocol A vs none in protocol B). Despite shorter duration of hypoglycemia, all subjects had adequate stimulated cortisol (>500 nmol/l) and hGH (>5 μg/l) levels. Mean peak concentrations of plasma ACTH (24 ± 12 pmol/l (A) vs 21 ± 8 pmol/l (B)), serum cortisol (690 ± 83 nmol/l vs 634 ± 83 nmol/l) and serum hGH (26 ± 16 μg/l vs 22 ± 13 μg/l) were slightly, but not significantly lower. In contrast, glucose infusion significantly reduced peak plasma epinephrine levels at 45 min (4.96 ± 4.91 pmol/l (A) vs 1.53 ± 1.1 pmol/l (B), P < 0.05) and ameliorated discomfort, as evaluated by a visual analog scale (P < 0.05).
Conclusions: Taken together, our pilot study suggests that, while the duration of hypoglycemia is shortened and acute epinephrine response is reduced, low-dose infusion of glucose does not significantly alter peak cortisol and growth hormone responses during ITT. Studies with a larger number of subjects and patients with suspected hypopituitarism are needed to further evaluate this modified protocol.
Diagnosis of hydatidiform mole and persistent trophoblastic disease: diagnostic accuracy of total human chorionic gonadotropin (hCG), free hCG α- and β-subunits, and their ratios
Authors: van Trommel Nienke E , Sweep Fred C G J , Schijf Charles P T , Massuger Leon F A G , Thomas Chris M G 
Published: September 2005

Objective: Human chorionic gonadotropin (hCG) is widely used in the management of hydatidiform mole and persistent trophoblastic disease (PTD). Predicting PTD after molar pregnancy might be beneficial since prophylactic chemotherapy reduces the incidence of PTD.Design: A retrospective study based on blood specimens collected in the Dutch Registry for Hydatidiform Moles. A group of 165 patients with complete moles (of which 43 had PTD) and 39 patients with partial moles (of which 7 had PTD) were compared with 27 pregnant women with uneventful pregnancy.Methods: Serum samples from patients with hydatidiform mole with or without PTD were assayed using specific (radio) immunoassays for free α-subunit (hCGα), free β-subunit (hCGβ) and ‘total’ hCG (hCG + hCGβ). In addition, we calculated the ratios hCGα/hCG + hCGβ, hCGβ/hCG + hCGβ, and hCGα/hCGβ. Specificity and sensitivity were calculated and paired in receiver-operating characteristic (ROC) curve analysis, resulting in areas under the curves (AUCs).Results: hCGβ, hCGβ/hCG + hCGβ and hCGα/hCGβ show AUCs ranging between 0.922 and 0.999 and, therefore, are excellent diagnostic tests to distinguish complete and partial moles from normal pregnancy. To distinguish partial from complete moles the analytes hCGβ, hCG + hCGβ and the ratio hCGα/hCGβ have AUCs between 0.7 and 0.8. Although hCGα, hCGβ and hCG + hCGβ concentrations are significantly elevated in patients who will develop PTD compared with patients with spontaneous regression after evacuation of their moles, in predicting PTD, these analytes and parameters have AUCs <0.7.Conclusions: Distinction between hydatidiform mole and normal pregnancy is best shown by a single blood specimen with hCGβ, but hCGβ/hCG + hCGβ and hCGα/hCGβ are also excellent diagnostic parameters. To predict PTD, hCGα, hCGβ, hCG + hCGβ and hCGα/hCGβ are moderately accurate tests, although they are not accurate enough to justify prophylactic chemotherapy treatment for prevention of PTD.
Testosterone supplementation in healthy older men drives GH and IGF-I secretion without potentiating peptidyl secretagogue efficacy
Authors: Veldhuis Johannes D , Keenan Daniel M , Mielke Kristi , Miles John M , Bowers Cyril Y 
Published: September 2005

Objective: Testosterone supplementation increases GH and IGF-I concentrations in healthy older men via unknown mechanisms. We examine the hypotheses that (i) testosterone amplifies stimulation of GH secretion by GH-releasing peptide (GHRP)-2 or GH-releasing hormone (GHRH) infused with l-arginine to limit somatostatin outflow (i.e. upregulates each agonistic pathway), (ii) testosterone augments the effect of both peptidyl secretagogues infused together (i.e. reduces opposition by hypothalamic somatostatin) and (iii) abdominal visceral fat (AVF) mass is a negative determinant of specific secretagogue-stimulated GH secretion.
Design: Randomized double-blind crossover design of placebo versus testosterone administration in healthy older men.
Methods: Deconvolution analysis was used to estimate basal GH secretion and the mass (integral) and waveform (time-shape) of GH secretory bursts.
Results: Statistical contrasts revealed that administration of testosterone compared with placebo in seven men aged 60–77 years increased fasting concentrations of GH (P < 0.01) and IGF-I (P = 0.003), and basal (P < 0.005) and pulsatile (P < 0.01) GH secretion. Testosterone did not alter the absolute value or rank order of secretagogue efficacy: l-arginine/GHRP-2 (23-fold effect over saline) = GHRH/GHRP-2 (20-fold) > l-arginine/GHRH (7.5-fold). Waveform reconstruction indicated that each stimulus pair accelerated initial GH secretion within a burst (P < 0.01). Regression analysis disclosed a significant inverse association between GH secretory-burst mass and computer tomography-estimated AVF following stimulation with l-arginine/GHRH after testosterone supplementation (R2 = 0.54, P = 0.015).
Conclusion: Supraphysiological testosterone concentrations augment GH and IGF-I production in the elderly male without altering maximal somatotrope responses to single and combined GHRH and GHRP-2 drive, thus predicting multifactorial mechanisms of testosterone upregulation.
Hormone-replacement therapy use, but not race, impacts the resting and exercise-induced GH response in postmenopausal women
Authors: Kanaley J A , Giannopoulou I , Collier S , Ploutz-Snyder R , Carhart R 
Published: September 2005

Objective: This study examined the effect of hormone-replacement therapy (HRT) use on the incremental GH response to aerobic exercise in postmenopausal women and established whether racial differences in the GH response were seen at rest and in response to exercise.
Methods: 13 white (n = 6, HRT; n = 7, no HRT) and seven black women (no HRT) were studied on two occasions, a control day and an exercise day (30 min at 70% VO2max on a cycle ergometer). Blood was sampled every 10 min for a 4-h period and analyzed for GH using an ultrasensitive chemiluminescent assay.
Results: The mean 4-h GH concentration was higher on both study days in the HRT women than the non-HRT users. The integrated GH concentrations were greater in the HRT women both at rest and in response to exercise (rest, 352 ± 53 min μg l−1; exercise, 711 ± 57 min μg l−1; P < 0.01) than in the non-HRT women (rest, 157 ± 87 min μg l−1; exercise, 248 ± 94 min μg l−1). The incremental GH response was greater in the HRT users than in the non-HRT women (358 ± 130 versus 90.8 ± 94 min μg l−1, respectively; P < 0.05). GH-production rate during the 4-h period was greater in the HRT women than in the non-HRT women (P < 0.01), due to an increase in the GH mass secreted/pulse (P < 0.05), with no change in GH pulse number or GH half-life. No racial differences in the mean 4-h GH concentrations or integrated GH concentrations were found at rest or in response to exercise.
Conclusion: HRT use resulted in a greater incremental exercise response compared with non-HRT users, due to changes in the secretory pulse characteristics in the HRT users. This study also demonstrated that no racial differences exist at rest and in response to exercise in the morning hours.
Assessment of gas‐fluidized beds mixing and hydrodynamics by zirconia sensors
Authors: Solimene Roberto , Marzocchella Antonio , Passarelli Gabriella , Salatino Piero 
Published: September 2005

AbstractGas‐mixing and bed hydrodynamics associated with the rise of isolated bubbles in gas‐fluidized beds of two granular solids are investigated by means of a novel technique. These diagnostics consist of an array of miniaturized zirconia‐based oxygen sensors located along the axis of a hot (1123 K) incipiently fluidized bed, in which isolated bubbles of a tracer gas (nitrogen) are injected. Time‐resolved oxygen concentrations and relative pressures are recorded at several levels along the bed. It is shown how the response of the sensors array can be related to the concurrent effects of bubble motion, bubble‐emulsion phase, mass transfer and interstitial gas flow in the emulsion phase, combined with each other to give rise to the propagation of two perturbations to the basal value of oxygen concentration. Analysis of time‐resolved oxygen concentration profiles enables the assessment of: (a) the bubble rise velocity; (b) the gas velocity associated with the interstitial flow; and (c) the interphase bubble‐emulsion phase, mass‐transfer rate and coefficient. Analysis of the response of sensors located in the splash zone of the fluidization column provides indirect inference of the hydrodynamic patterns associated with bubble bursting at the surface of the bed. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Long‐term remission of blastic natural killer‐cell lymphoma after autologous peripheral blood stem‐cell transplantation
Authors: Yamaguchi Masaki , Maekawa Mio , Nakamura Yoshihisa , Ueda Mikio 
Published: September 2005

AbstractWe report here a case of blastic natural killer (NK)‐cell lymphoma treated successfully with autologous peripheral blood stem‐cell transplantation (APBSCT). A 57‐year‐old man had skin tumors and was diagnosed as having blastic NK‐cell lymphoma by tumor biopsy. Skin, lymph nodes, left tonsil, and bone marrow were involved at presentation. Chemotherapy led to complete remission (CR). To sustain CR, the patient underwent high‐dose chemotherapy in combination with 12 Gy of total‐body irradiation (TBI) followed by autologous peripheral blood stem‐cell rescue. He showed rapid recovery of hematopoiesis and could tolerate regimen‐related toxicity after APBSCT. He has maintained long‐term remission for 20 months after APBSCT. From this case, we concluded that APBSCT with preconditioning by TBI‐containing regimens might be a cure‐attaining treatment for disseminated blastic NK‐cell lymphoma and should be considered as a choice of treatment in cases where no suitable donors for allogeneic transplantation are available. Am. J. Hematol. 80:124–127, 2005. © 2005 Wiley‐Liss, Inc.
Hypereosinophilic syndrome: An update
Authors: Wilkins H. Jeffrey , Crane Martin M. , Copeland Kelly , Williams William V. 
Published: September 2005

AbstractHypereosinophilic syndrome (HES) is a rare disorder that is characterized by persistent and marked eosinophilia combined with organ system dysfunction. HES has substantial clinical heterogeneity but can be fatal without treatment, especially in patients who present with a myelodysplastic variant of the disorder. Although the pathophysiology of HES is poorly defined, dysregulation of cytokines (interleukin 5 [IL‐5], IL‐3, granulocyte‐macrophage colony‐stimulating factor [GM‐CSF]) responsible for the maturation of eosinophils is a primary feature. Of these cytokines, IL‐5 appears to have the greatest role in the regulation of eosinophil maturation. There is no Food and Drug Administration‐approved treatment for HES as yet; current strategies are designed to lower blood eosinophils and attempt to limit end‐organ damage. Historically, corticosteroids and cytotoxic agents have been the mainstays of therapy, with biological response modifiers such as interferon‐alpha also effective in some patients. However, despite improvements in survival, available agents have significant limitations in terms of efficacy, tolerability, and long‐term toxicity. More recently, new agents directed at specific targets in the pathogenesis of HES have been developed. These include imatinib mesylate, a tyrosine kinase inhibitor, and more recently, mepolizumab, an anti‐IL‐5 monoclonal antibody. In a small case series of patients, these agents have been shown to produce hematological and clinical responses in patients with HES, although they may be effective in different subsets of patients. These targeted therapies have the potential to improve clinical outcomes and to further the understanding the pathophysiology of this difficult‐to‐treat condition. Am. J. Hematol. 80:148–157, 2005. © 2005 Wiley‐Liss, Inc.
Compound heterozygote state for GγAγ(δβ)°‐thalassemia and hereditary persistence of fetal hemoglobin
Authors: Fucharoen Supan , Panyasai Sitthichai , Surapot Satja , Fucharoen Goonnapa , Sanchaisuriya Kanokwan 
Published: September 2005

AbstractWe report a hitherto undescribed interaction of a deletional (δβ)°‐thalassemia and a deletional hereditary persistence of fetal hemoglobin (HPFH) in an adult Thai individual. He was a 40‐year‐old Thai male who had the following hematologic data: Hb 13.9 g/dL, Hct 43.8%, MCV 78.0 fL, MCH 24.7 pg, MCHC 31.6 g/dL, and RDW 17.1%. Hemoglobin analysis revealed 97% Hb F with Gγ‐globin chain predominant. Globin gene analyses demonstrated that he carried the GγAγ(δβ)°‐thalassemia deletion in trans to the HPFH‐6. Hematologic data of the patient were compared to those of the heterozygotes for these high‐Hb F determinants found in his parents and an unrelated Thai patient with a compound HPFH‐6/deletion–inversion Gγ(Aγδβ)°‐thalassemia previously described. Am. J. Hematol. 80:119–123, 2005. © 2005 Wiley‐Liss, Inc.
Differential effect of IL‐15 and IL‐2 on survival of phytohemagglutinin‐activated umbilical cord blood T cells
Authors: Lin Syh‐Jae , Cheng Po‐Jen , Hsiao Shiu‐Shan , Lin Hui‐Hao , Hung Pei‐Fen , Kuo Ming‐Ling 
Published: September 2005

AbstractCytokine immunotherapy using interleukin (IL)‐2 and IL‐15 may be beneficial for patients receiving umbilical cord blood (CB) transplantation by ameliorating post‐transplant T‐cell apoptosis. The present study compares the differential effect of IL‐15 and IL‐2 on survival of phytohemagglutinin (PHA)‐activated CB and adult peripheral blood (APB) T lymphocytes. In comparison with IL‐2, IL‐15 preferentially enhanced the survival of CB PHA‐activated T cells by decreasing the caspase‐3+ population and by increasing the Bcl‐2+ population. Activated CB T cells were more susceptible to TNF‐α‐induced apoptosis compared to their adult counterparts. However, the susceptibility could be abrogated by IL‐15 but not by IL‐2. IL‐15 but not IL‐2 down‐regulated CD28 expression on both activated CB and APB CD8+ T cells, with a much greater effect seen with CB. Western‐blot analysis shows that IL‐15 Rα is deficient in CB compared to APB immediately after PHA stimulation, while culturing with IL‐15 significantly enhanced CB IL‐15 Rα expression to levels comparable to that of adults. Thus, IL‐15 may provide a better therapeutic choice for immune reconstitution than IL‐2 post‐CB transplantation due to its preferential survival enhancing effect on CB T cells. Am. J. Hematol. 80:106–112, 2005. © 2005 Wiley‐Liss, Inc.
Analysis of outcome of laparoscopic splenectomy for idiopathic thrombocytopenic purpura by platelet count
Authors: Keidar A. , Feldman M. , Szold A. 
Published: September 2005

AbstractLaparoscopic splenectomy (LS) is now performed routinely in patients with idiopathic thrombocytopenic purpura (ITP) refractory to the medical treatment. Low preoperative platelet count was deemed to be a contraindication for a laparoscopic approach; however, there is no data reporting the outcome in those patients. We aimed to evaluate the influence of the preoperative platelet count on the operative and postoperative course and complication rate. Retrospective cohort study that was conducted in tertiary care university‐affiliated medical center and included 110 consecutive patients who underwent LS. All patients were divided into three groups by their preoperative platelet counts: ≤20 × 109/L (n = 12), (20–50) × 109/L (n = 18), and >50 × 109/L (n = 80). The outcome and the influence of preoperative factors predictive of complications, blood transfusion, and length of stay were compared between the groups. Patients with a platelet count of ≤20 × 109/L had a much longer hospital stay, received more blood transfusions, and suffered more complications than patients with platelet counts of (20–50) × 109/L or higher (P < 0.05). Transfused patients had a longer hospital stay than non‐transfused patients (2.08 vs. 6.4 days, P = 0.029). The strongest predictor for transfusion was the platelet count (odds ratio = 23, P = 0.008). LS in patients with very low platelet counts is feasible and reasonably safe, but the platelet count is a major determinant of morbidity. Every effort should be made to elevate platelet levels to >20 × 109/L before surgery. Patients with counts >20 × 109/L can safely undergo LS. Am. J. Hematol. 80:95–100, 2005. © 2005 Wiley‐Liss, Inc.
Bone mineral density and serum bone turnover markers in survivors of childhood acute lymphoblastic leukemia: Comparison of megadose methylprednisolone and conventional‐dose prednisolone treatments
Authors: Alikasifoglu Ayfer , Yetgin Sevgi , Cetin Mualla , Tuncer Murat , Gumruk Fatma , Gurgey Aytemiz , Yordam Nursen 
Published: September 2005

AbstractDuring recent decades, the survival rate after childhood acute lymphoblastic leukemia (ALL) has improved substantially; consequently, the long‐term side effects of ALL and its treatment have gained attention, of which osteoporosis is one of the most important. The purpose of the present study was to compare the influence of different treatment protocols that include high‐dose methylprednisolone (HDMP) versus conventional‐dose prednisolone (CDP) for remission‐induction therapy on bone mineral density (BMD) and serum bone turnover markers in survivors of childhood ALL after cessation of chemotherapy. Thirty‐six boy and 23 girl survivors, treated for ALL, were cross‐sectionally studied, at a mean age of 11.7 years (range 6–19). Group 1 (n = 30) received CDP therapy (prednisolone, 2 mg/kg/day, orally) and group 2 (n = 29) received HDMP therapy (prednol‐L, 900–600 mg/m2, orally). All other therapies were similar in both groups. Cranial irradiation was added for high‐risk patients as soon as possible after consolidation therapy. We found that mean lumbar spine BMD z score value was −1.75 (0.83) SDS in group 1 and −1.66 (1.21) SDS in group 2. There is no difference between both groups (P = 0.736). The mean BMD z scores of prepubertal and pubertal patients were not significantly different in both groups. Comparison of serum bone turnover parameters of the patients revealed no difference between the two groups. Stepwise regression analysis revealed that lumbar spine BMD z scores was predicted by height SDS and the time past since cessation of therapy, but not age at diagnosis, BMI SDS, cranial radiotherapy, and puberty. Our study results showed that HDMP treatment did not deteriorate the bone mass any more than CDP treatment. These results proved that high‐dose steroid therapy over a short period of time in remission‐induction treatment would not affect the bone mass any more adversely than would conventional doses approximately 3 years after cessation of chemotherapy. Am. J. Hematol. 80:113–118, 2005. © 2005 Wiley‐Liss, Inc.
Adenosine A2A receptor dysfunction correlates with age at onset anticipation in blood platelets of subjects with Huntington's disease
Authors: Maglione V. , Giallonardo P. , Cannella M. , Martino T. , Frati L. , Squitieri F. 
Published: September 2005

AbstractHuntington's disease (HD) may manifest at an earlier age in affected offspring than in transmitting parents. Earlier onset in successive generations (anticipation) only partially depends on intergenerational parent–child elongation of the CAG expanded mutation. An aberrant amplification of adenosine A2A receptor signaling documented in peripheral blood cells of subjects with HD implies that this cellular dysfunction may be related to clinical and genetic features. Prompted by evidence of higher receptor densities in siblings of HD subjects with stronger onset anticipation, in this study we investigated a possible relationship between A2A receptor densities and age at onset. We measured adenosine A2A receptor densities in blood cell platelets from 32 patients with HD and healthy control siblings, and sought a possible linear correlation between maximum platelet A2A receptor binding (Bmax) values for the whole cohort of HD subjects and anticipation in years. The increased Bmax values for the 32 subjects with HD (220 in patients vs. 137 in healthy control subjects, P = 0.0001) correlated significantly with anticipation in years (r2, 0.48, P = 0.0001 by linear correlation analysis). An increased platelet A2A receptor Bmax may belong in a cascade of toxic events leading to earlier onset of HD: as such it could be a useful marker of onset anticipation. © 2005 Wiley‐Liss, Inc.
Haplotype diversity and somatic instability in normal and expanded SCA8 alleles
Authors: Martins Sandra , Seixas Ana I. , Magalhães Paula , Coutinho Paula , Sequeiros Jorge , Silveira Isabel 
Published: September 2005

AbstractSpinocerebellar ataxia type 8 (SCA8) is an autosomal dominant late‐onset neurodegenerative disorder, belonging to the group of diseases caused by trinucleotide repeat expansions. SCA8 remains one of the most intriguing SCAs, regarding the reduced disease penetrance, and the high instability and poorly understood functional meaning of the (CTA)n(CTG)n expansion. We performed haplotype and sequencing analysis in a large region, encompassing the repeat, in four SCA8 and 20 control Portuguese families. The results from the haplotype study including the combined repeat and six SNP markers showed two different haplotypes, AG‐Exp‐GTTG and AG‐Exp‐CTTG, in the SCA8 families. Among the control population, these were also the most frequent, in a total of five haplotypes found unequally distributed throughout repeat sizes. From cloning fragments of control, unstable normal and expanded chromosomes, eleven different base substitutions were identified in exon A of the SCA8 gene. In some instances, somatic variability in repeat size or base composition was found for a same chromosome, regardless of its normal or expanded nature. In conclusion, our results in Portuguese families with ataxia show that SCA8 expansions arose in common backgrounds; in addition, this region seems to be unstable beyond the repeat. © 2005 Wiley‐Liss, Inc.