bluuebunny/crossref_metadata_2025_split huggingface dataset:
Giant prolactinomas in men: efficacy of cabergoline treatment
Authors: Corsello S. M. , Ubertini G. , Altomare M. , Lovicu R. M. , Migneco M. G. , Rota C. A. , Colosimo C. 
Published: December 2004

Summaryobjective The term ‘giant prolactinoma’ can be used for tumours larger than 4 cm in diameter and/or with massive extrasellar extension. Cabergoline (CAB), a long‐lasting dopamine agonist (DA), safe and well tolerated, is effective in normalizing PRL levels and inducing tumour shrinkage in micro‐ and macroprolactinomas. The purpose of this prospective study was to evaluate the efficacy and safety of CAB also for giant prolactinomas.patients and methods Ten men with giant prolactinomas with a median age of 44·8 years were treated with CAB. Before CAB, four patients had previously undergone transsphenoidal surgery without modifying the parasellar extension of the tumour or their visual defects. Pretreatment serum prolactin (PRL) levels ranged between 1230 and 22 916 µg/l (mean ± SEM: 5794 ± 1996) and tumour volume was between 21·8 and 105·5 cm3 (mean ± SEM: 50·7 ± 8·8).CAB was administered at an initial low dose of 0·5 mg three times a week and, in five patients who did not achieve serum PRL normalization, the dose was progressively increased up to 10·5 mg/week. The duration of treatment was 13–68 months (mean 38·9). PRL levels and pituitary target organ hormones were assayed before, after 30 days and then every 3 months after the beginning of CAB treatment. Magnetic resonance imaging (MRI) was carried out before, after 1–3 months, after 6 months and then every 10–12 months to evaluate tumour shrinkage.results In every patient, a significant PRL decrease (P = 0·0086) of at least 96% of the pretreatment values occurred (from 5794 ± 1996 to 77 ± 38, mean ± SEM); a persistent normalization of PRL levels was achieved in five out of 10 patients (50%) beginning from the first 3–6 months of CAB treatment (only one patient needed 12 months of therapy). A significant tumour shrinkage (P = 0·0003) was achieved after 12 months of therapy in nine out of 10 patients (90%), with a volume reduction greater than 95% in three, of 50% in four and 25% in two patients. Tumour volume decreased from 50·7 ± 8·8 to 28·6 ± 9·4 and then to 22·3 ± 8·8 cm3 (mean ± SEM) after 6 and 12 months of CAB treatment, respectively. An improvement of visual field defects (VFD) was obtained in six of the seven patients presenting visual impairment before CAB treatment. Among the eight patients presenting libido and potency (L‐P) failure, five normalized their PRL levels. In two of these a complete restoration of libido and potency was observed. Three patients with secondary hypoadrenalism and a patient with secondary hypothyroidism were treated with substitutive therapy during all the study time. The drug was well tolerated by all patients and no one discontinued the therapy.conclusions These data suggest that, in giant, aggressive prolactinomas, CAB represents a first‐line therapy effective in reducing PRL levels and determining tumour shrinkage.
Adrenarche – physiology, biochemistry and human disease
Authors: Auchus Richard J. , Rainey William E. 
Published: December 2004

SummaryAdrenarche refers to the onset of dehydroepiandrosterone (DHEA) and DHEA‐sulphate (DHEA‐S) production from the adrenal zona reticularis that can be detected at around 6 years of age. The phenotypic result of adrenarche is pubarche or the development of axillary and pubic hair that occurs in both girls and boys at about age 8. The phenomenon of adrenarche is unique to human beings and to some Old World primates, and a reversal of adrenarche appears to occur in the ageing process. Premature and exaggerated adrenarche can be indicative of future onset of adult diseases, thus increasing the clinical relevance of adrenarche. The physiological triggers of adrenarche and the role(s) of DHEA‐S remain speculative. However, the biochemical pathways that define adrenarche have been characterized in detail, and the appearance of key enzymes and cofactors in the adrenal zona reticularis track with the progression of adrenarche. This article reviews the clinical manifestations of adrenarche, the biochemistry of the enzymes involved in DHEA‐S production, and the cell biology of the adrenal zona reticularis.
Management of adrenocortical carcinoma
Authors: Allolio Bruno , Hahner Stefanie , Weismann Dirk , Fassnacht Martin 
Published: December 2004

SummaryAdrenocortical carcinoma (ACC) is a rare neoplasm with poor prognosis. Patients present with signs of steroid hormone excess (e.g. Cushing's syndrome, virilization) or an abdominal mass. Tumour size at presentation (mean diameter at diagnosis > 10 cm) is the most important indicator of malignancy. In addition, computed tomography (CT) typically demonstrates an inhomogeneous adrenal lesion with irregular margins and variable enhancement of solid components after intravenous contrast media. Magnetic resonance imaging (MRI) is equally effective as CT and is particularly helpful to visualize invasion into large vessels. Complete tumour removal (R0 resection) offers by far the best chance for long‐term survival and therefore surgery is the treatment of choice in stage I–III ACC. Despite tumour resection for cure most patients will eventually develop local recurrence or distant metastases. Thus adjuvant treatment options need to be evaluated in high‐risk patients (e.g. radiation therapy of the tumour bed and/or chemotherapy). In tumour recurrence re‐operation should always be considered. In metastatic disease (stage IV ACC) not amenable to surgery mitotane (o,p′DDD) remains the first‐line therapy. Drug monitoring is needed for effective treatment aiming at concentrations between 14 and 20 mg/l. Patients not responding to mitotane may benefit from cytotoxic chemotherapy (23% partial remissions, 4% complete remissions). Only large prospective multicentre trials comparing different treatment options will allow to make systematic progress in the management of ACC.
Early postoperative indicators of late outcome in acromegalic patients
Authors: Takahashi Jun A. , Shimatsu Akira , Nakao Kazuwa , Hashimoto Nobuo 
Published: December 2004

Summaryobjective  According to current criteria, normalised serum IGF‐1 and glucose‐suppressed GH < 1 ng/ml are indicators of biochemical cure in acromegalic patients. We performed a retrospective study to assess whether the attainment of these values in the early postoperative period was predictive of future IGF‐1 normalisation and disease inactivity.patients, measurements and results  Between 1978 and 1999, 78 acromegalic patients underwent resection for pituitary adenomas. At the end of the mean follow‐up period of 7 years, 43 (55·1%) showed normalised IGF‐1 levels and no disease activity. In 51 cases, both IGF‐1 and glucose‐suppressed GH were examined within the first postoperative month. Of this group, all 19 patients who had early glucose‐suppressed GH < 1 ng/ml and were treated by surgery alone maintained normal IGF‐1 levels throughout the follow‐up; four of them demonstrated delayed (i.e. more than 30 days after the operation) IGF‐1 normalisation. In 19 patients with early glucose‐suppressed GH levels of 1–4 ng/ml, seven of 11 patients with early normalised IGF‐1 and two of eight patients with early IGF‐1 elevation manifested eventual IGF‐1 normalisation. However, none of the 13 patients with early glucose‐suppressed GH > 4 ng/ml attained IGF‐1 normalisation. Both univariate and multivariate analyses indicated that early glucose‐suppressed GH was a significant factor for predicting late normalised IGF‐1; the cut‐off value was 1·5 ng/ml (sensitivity: 0·97; specificity: 0·75; odds ratio: 90).conclusion  The attainment of both normalised IGF‐1 and glucose‐suppressed GH < 1 ng/ml, even during the early postoperative period, suggests absolute cure in acromegalic patients. However, even in patients who do not meet both criteria within the first postoperative month, glucose‐suppressed GH < 1·5 ng/ml, or glucose‐suppressed GH < 4 ng/ml coupled with early IGF‐1 normalisation indicate the possibility of eventual normalisation of IGF‐1 and disease inactivity without adjuvant therapy. These postoperative parameters may be useful for assessing the desirability of further treatment.
Successful treatment of childhood‐onset Cushing's disease is associated with persistent reduction in growth hormone secretion
Authors: Carroll P. V. , Monson J. P. , Grossman A. B. , Besser G. M. , Plowman P. N. , Afshar F. , Savage M. O. 
Published: December 2004

Summaryobjective  Although Cushing's disease (CD) rarely occurs in childhood, affected children commonly fail to achieve predicted adult height. Hypercortisolaemia results in reduced GH secretion and GH‐deficiency may persist or demonstrate delayed recovery after successful treatment of CD in adults. Whether recovery of spontaneous GH secretion occurs following treatment of childhood CD has yet to be established.design and patients  We performed a retrospective analysis of the GH status of 13 children (10 males; 12·8 ± 1·0 years, mean ± SE) who had undergone successful treatment of CD that occurred prior to the completion of linear growth. Each underwent transsphenoidal hypophysectomy, resulting in satisfactory control of glucocorticoid levels in 7/13 (54%). The remaining six patients (46%) received fractionated external beam irradiation (4500 Gy). At the time of GH assessment, circadian dynamics of cortisol were normal in eight patients and five were receiving titrated glucocorticoid replacement.measurements  GH status was assessed using the peak response to a provocative stimulus. Eleven out of 13 underwent testing with insulin‐induced hypoglycaemia (nadir plasma glucose ≤ 2·2 mmol/l) and glucagon provocation was used in 2/13. Severe GH‐deficiency was defined as a peak GH response < 9 mU/l, and a normal response as > 30 mU/l. Intermediate values were taken to represent subnormal GH status. Assessment of GH status was performed 39 ± 10 months (median ± SE) following successful treatment (range 9–108 months).results  Using these criteria 4/13 (31%) patients had severe GH‐deficiency. Only 2/13 (15%) had a normal response. 7/13 (54%) achieved peak GH levels in the subnormal range. Those with multiple pituitary hormone deficiencies were most likely to have lower peak GH levels, but there was no clear effect of pituitary irradiation or relationship between duration post cure and peak GH response.conclusion   GH‐deficiency is common and may persist for many years following successful treatment of CD prior to completion of linear growth. External radiotherapy does not necessarily result in severe GH‐deficiency in the short term. Assessment of GH status and consideration of GH treatment should be considered following treatment of CD in childhood and adolescence in order to maximize the opportunities to achieve a satisfactory final adult height. In those with subnormal GH responses, continued assessment is necessary to determine whether the GH axis subsequently recovers or if these patients develop features of the adult GH‐deficiency syndrome.
Effects of oral contraceptives on circulating osteoprotegerin and soluble RANK ligand serum levels in healthy young women
Authors: Hofbauer Lorenz C. , Schoppet Michael , Schüller Per , Viereck Volker , Christ Michael 
Published: December 2004

Summaryobjective  Osteoprotegerin (OPG) represents a secreted cytokine which regulates bone mass by blocking receptor activator of nuclear factor‐κB ligand (RANKL), the principal regulator of osteoclast function. In vitro, OPG production is upregulated by oestrogens in osteoblastic lineage cells, a mechanism that has been discussed as a protective paracrine mechanism of oestrogens on the skeleton. To define the effects of oestrogens on the RANKL/OPG system in vivo, we evaluated OPG and both free and total soluble RANKL (sRANKL) serum levels in healthy young women with or without oral contraceptives.design and patients  Serum levels of OPG and sRANKL were prospectively assessed in a cohort of healthy young women with (n = 30) or without (n = 25) combined oestrogen–progestin‐based oral contraceptives.measurements  OPG, total and free sRANKL serum levels were determined by enzyme‐linked immunosorbent assays (ELISA).results  In women using oral contraceptives, OPG serum levels were significantly higher (2·71 ± 1·42 pmol/l) compared to nonusers (1·35 ± 1·02 pmol/l; P = 0·0003), whereas free (P = 0·55) and total (P = 0·24) sRANKL serum levels did not differ between both groups. This resulted in an increased OPG/free sRANKL ratio (P = 0·02) in women on oral contraceptives. During the ovarian cycle, OPG (P = 0·22) and free sRANKL (P = 0·99) serum levels remained unchanged in women without oral contraceptives (n = 19), while total sRANKL levels were higher in the follicular than in the luteal phase (P = 0·02).conclusions  Intake of oral contraceptives is associated with increased OPG serum levels, but not sRANKL levels, resulting in a higher OPG/sRANKL ratio. This may contribute to the positive effects of oral contraceptives on the skeleton.
Effects of conjugated oestrogen and droloxifene on the renin–angiotensin system, blood pressure and renal blood flow in postmenopausal women
Authors: Seely Ellen W. , Brosnihan K. Bridget , Jeunemaitre Xavier , Okamura Kyoko , Williams Gordon H. , Hollenberg Norman K. , Herrington David M. 
Published: December 2004

Summaryobjective  The aim of this study was to evaluate the effect of conjugated equine oestrogen (CEE), and droloxifene, a selective oestrogen receptor modulator (SERM) on individual components of renin–angiotensin–aldosterone (RAAS) and blood pressure (BP) in postmenopausal women.design and patients  Twenty‐one normotensive (NT) and 10 hypertensive (HT) postmenopausal women received either CEE (0·625 mg/day) or droloxifene (60 mg/day) for 6 weeks and, after a 4‐week washout, were restudied on the alternate medication.measurements  Hormones of the RAAS and supine BP were measured prior to and at the end of each drug treatment in all subjects. In a subgroup of the NT (n = 10), 24 h ambulatory BP was performed and renal blood flow was determined by PAH clearance both basally and in response to 45‐min angiotensin II (Ang II) infusion (3 ng/kg/min).results  CEE significantly increased angiotensinogen, decreased active renin and angiotensin‐converting enzyme (ACE), and maintained plasma immunoreactive (ir) angiotensin I (Ang I) levels compared to baseline. With droloxifene, angiotensinogen, active renin and Ang I remained unchanged. Both CEE and droloxifene significantly increased plasma ir–Ang II levels (pmol/l) in NT (baseline: 25·7 ± 2·5, CEE: 36·6 ± 3·4, droloxifene: 33·3 ± 3·1, P < 0·002) and HT women (baseline: 17·9 ± 2·3, CEE: 27·9 ± 3·2, droloxifene: 25·9 ± 4·9, P < 0·005). Renal blood flow was lower on CEE (P = 0·02) compared with baseline. Systemic BP (supine and 24‐h ambulatory) was unchanged during both treatments.conclusion  This study demonstrates higher circulating levels of ir–Ang II with CEE and droloxifene.
Post‐liver transplant acute renal failure: factors predicting development of end‐stage renal disease*
Authors: Paramesh Anil S , Roayaie Sasan , Doan Yvette , Schwartz Myron E , Emre Sukru , Fishbein Thomas , Florman Sander , Gondolesi Gabriel E , Krieger Nancy , Ames Scott , Bromberg Jonathan S , Akalin Enver 
Published: December 2004

Abstract:  Background:  Acute renal failure (ARF) occurs in 5–50% ofpatients undergoing orthotopic liver transplantation (OLT). The aim of this study was to determine factors that might predict the development of end stage renal disease (ESRD) in patients who had ARF after OLT.Methods:  We studied all OLT recipients between 9/1/1988 through 12/31/2000.Results:  A total of 1602 patients underwent OLT during the study period. About 350 patients (22%) developed ARF requiring dialysis post‐operatively. One hundred and twenty‐three (39.8%) died within a year after OLT. Median follow up was 5.8 yr (range 1–12 yr). Forty‐three patients (23%) developed ESRD over median of 3.79 yr (range 1–8 yr). Multivariate logistic regression analysis revealed creatinine levels >1.7 mg/dL at 1 yr (p < 0.001), cyclosporine as immunosuppression (p = 0.026), and the presence of diabetes pre‐OLT (p < 0.001) to be associated with the development of ESRD. The development of ESRD did not decrease patient survival (p = 0.111). ESRD patients who received subsequent kidney transplantation had significantly improved survival rates (p = 0.005).Conclusions:  Serum creatinine levels at 1 yr, cyclosporine as immunosuppression, and the presence of diabetes pre‐OLT are independent predictive factors for the development of ESRD. ESRD patients who received kidney transplantation had higher10‐yr survival rates when compared with patients maintained on dialysis.
Cardiovascular and renal phenotyping of genetically modified mice: A challenge for traditional physiology
Authors: Fitzgerald Sharyn M , Gan Liming , Wickman Anna , Bergström Göran 
Published: December 2004

Summary1. The advent of techniques to genetically modify experimental animals and produce directed mutations in both a conditional and tissue‐specific manner has dramatically opened up new fields for physiologists in cardiovascular and renal research.2. A consequence of altering the genetic background of mice is the difficulty in predicting the phenotypic outcome of the genetic mutation. We therefore suggest that physiologists may need to change their current experimental paradigms to face this new era. Hence, our aim is to propose a complementary research philosophy for physiologists working in the post‐genomic era. That is, instead of using strictly hypothesis‐driven research philosophies, one will have to perform screening studies of mutant mice, within a field of interest, to find valuable phenotypes. Once a relevant phenotype is found, in‐depth studies of the underlying mechanisms should be performed. These follow‐up studies should be performed using a traditional hypothesis‐driven research philosophy.3. The rapidly increasing availability of mutated mouse models of human disease also necessitates the development of techniques to characterize these various mouse phenotypes. In particular, the miniaturization and refinement of techniques currently used to study the renal and cardiovascular system in larger animals will be discussed in the present review. Hence, we aim to outline what techniques are currently available and should be present in a laboratory to screen and study renal and cardiovascular phenotypes in genetically modified mice, with particular emphasis on methodologies used in the intact, conscious animal.
Nucleotides modulate renal ischaemia–reperfusion injury by different effects on nitric oxide and superoxide
Authors: López‐Martí J , Sola A , Pi F , Alfaro V , Marco A , Hotter G 
Published: December 2004

Summary1. The present study investigated the effects of kidney ischaemia duration on nitric oxide (NO) and superoxide (O2–) generation at reperfusion and the role of xanthine and adenosine as mediators of NO/O2– generation.2. The effect of the duration of ischaemia on renal nucleotide levels was studied in two ischaemic groups (10 and 30 min). The role of adenosine and xanthine was studied in ischaemic–reperfused groups (subjected to 10 and 30 min ischaemia and 60 min reperfusion).3. Tissue levels of adenosine decreased significantly after 30 min ischaemia, whereas xanthine/hypoxanthine levels increased concomitantly with renal dysfunction and histological damage.4. Nitric oxide production increased significantly after 10 min ischaemia and 60 min reperfusion, whereas lipoperoxidation increased significantly after 30 min ischaemia and 60 min reperfusion. The administration of theophylline (40 mg/kg, i.p.) reversed the early increase in NO production.5. Xanthine supplementation decreased renal function and increased lipoperoxidation.6. In conclusion, NO/O2– production and the subsequent renal injury/dysfunction may be modified by changes in the adenosine and xanthine levels of the injured kidney, although the present data show a significant in vivo role only for xanthine.
Low‐affinity neurotrophin receptor with targeted mutation of exon 3 is capable of mediating the death of axotomized neurons
Authors: Murray Simon S , Bartlett Perry F , Lopes Elizabeth C , Coulson Elizabeth J , Greferath Una , Cheema Surindar S 
Published: December 2004

Summary1. In vivo studies have shown that the low‐affinity 75 kDa neurotrophin receptor (p75NTR) is involved in axotomy‐induced cell death of sensory and motor neurons. To further examine the importance of p75NTR in mediating neuronal death in vivo, we examined the effect of axotomy in the p75NTR‐knockout mouse, which has a disrupted ligand‐binding domain.2. The extent of sensory and motor neuron loss in the p75NTR‐knockout mouse following axotomy was not significantly different to that in wild‐type mice. This suggests that disruption of the ligand‐binding domain is insufficient to block the cell death process in axotomized neurons.3. Immunohistochemical studies showed that axotomized neurons continue to express this mutant receptor with its intracellular death‐signalling moiety intact.4. Treatment with antisense oligonucleotides targeted against p75NTR resulted in significant reduction in the loss of axotomized neurons in the knockout mouse.5. These data suggest that the intracellular domain of p75NTR is essential for death‐signalling and that p75NTR can signal apoptosis, despite a disrupted ligand‐binding domain.
Effects of dietary Angelica keiskei on lipid metabolism in stroke‐prone spontaneously hypertensive rats
Authors: Ogawa Hiroshi , Nakashima Seiji , Baba Kimiye 
Published: December 2004

Summary1. The effect of dietary Angelica keiskei on lipid metabolism was examined in stroke‐prone spontaneously hypertensive rats (SHRSP).2. Six‐week‐old male SHRSP were fed diets containing 0.2% A. keiskei extract (ethyl acetate extract from the yellow liquid of stems) for 6 weeks with free access to the diet and water.3. Elevation of systolic blood pressure tended to be suppressed on and after 2 weeks; however, this effect was not statistically significant.4. Serum levels of cholesterol and phospholipid in SHRSP were significantly elevated after treatment with A. keiskei extract and this effect was accompanied by significant increases in serum apolipoprotein (Apo) A‐I and ApoE concentrations. These changes in the serum were due to increases in high‐density lipoprotein (HDL) containing ApoA‐I and ApoE.5. In the liver, significant decreases in relative weight and triglyceride content were observed in SHRSP after treatment with A. keiskei extract. An investigation of mRNA expression of enzymes involved in hepatic triglyceride metabolism indicated a decreased level of hepatic Acyl‐coenzyme A synthetase mRNA expression.6. In conclusion, dietary A. keiskei produces elevation of serum HDL levels and a reduction of liver triglyceride levels in SHRSP.