Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies.

RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation.

Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies

RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation.

New insight on the molecular aspects of glucocorticoid effects in nervous system development.

Adrenal glucocorticoids (Gc) are among the most significant hormones in the mammalian organisms; these steroids may reach and penetrate all tissues where they interact with cytoplasmic/nuclear receptors, through which they exert multiple and very multifaceted actions. The effects of physiological concentrations of Gc on brain functions have not been completely clarified, even though Gc are recognized to influence behavioral responses, emotions, cognitive processes and to take part in the neuroendocrine control of body homeostasis. Developmental programming effects of Gc in animal models and humans have been proposed. Actually, pre-natal stress, or exposure to high Gc levels, would somehow affect neuronal developmental events in some structure and this can lead to central nervous system altered functions, as the impairment of neuroendocrine activities, cognitive processes, sleep and mood disorders. Interestingly, it has been observed that these abnormalities may not be limited to the first directly exposed individuals but transmissible across generations. The establishment of animal models with localized pre-natal glucocorticoid receptors deficiency led to the accumulation of data on the possible roles of these hormones on development of the central and peripheral nervous system. The most recent findings on the effects of Gc on neuroblast development, with particular attention to neuronal migration, will be presented.

Kyphoplasty versus percutaneous vertebroplasty using the traditional and the new side-opening cannula for osteoporotic vertebral fracture.

AIM: The aim of this article was to study the results of two different types of percutaneous vertebroplasty (PV) and kyphoplasty (KPs) to osteoporotic vertebral fractures (OVF). METHODS: It was prospectively analyzed a series of 47 PVs from January 2003 to February 2008, and a consecutive series 30 KPs from March 2008 to January 2010, performed for patients with painful OVFs. Twenty-five PVs were performed using the frontal-opening cannula (FOC) and 22 using the new side-opening cannula (SOC), randomly distributed in the PV group. RESULTS: The incidence of cement extrusion was 16.7% with KP, comparing with PV, it was 27.3% using the SOC (P<0.05) and 68,0% with the FOC (P<0.05), but comparing SOC with FOC, the cement extrusion was significantly lower using the SOC (P<0.05), all asymptomatic. The pain control was similar for all groups (P<0.05), with good improvement of pain in most of the patients, and there were no clinical relevant complications. CONCLUSION: The cement leakage was significantly reduced with the KP (16.7%) and the SOC (27.3%) for PV, in comparison with the FOC (68.0%). The cement extrusion was slightly lower with KP, but not a significant difference, comparing with SOC, increasing the safety of the procedure using both the KP and this new SOC.

Effects of metformin and short-term lifestyle modification on the improvement of male hypogonadism associated with metabolic syndrome.

AIM: The metabolic syndrome is associated with male hypogonadism, but specific studies about the mechanisms and treatment of the testosterone deficit are scanty. The aim of this study was to evaluate the effects of metformin combined with diet and physical activity on the testicular function of men with metabolic syndrome. METHODS: Thirty-five men (40.4 ± 13.3 years old) with metabolic syndrome were evaluated before and after a four-month period of therapy with metformin 850 mg twice daily, associated with a balanced normocaloric diet and subtle improvement in physical activity. The subjects were divided in two groups: 21 males with normal plasma testosterone levels (≥ 300 ng/dL) and 14 males with low plasma testosterone levels (< 300 ng/dL). RESULTS: There was a significant decrease in fasting insulin levels and HOMA-IR after treatment (P = 0.01 and P = 0.06), which was more pronounced in the hypogonadic group (for the effect of absence or presence of hypogonadism, P = 0.04). The mean total and free testosterone levels increased significantly after treatment in both groups, similarly. The increase in FSH levels was more pronounced in the hypogonadic group than in the eugonadic group. CONCLUSION: In this series of males with metabolic syndrome, treatment with metformin associated with healthy dietary modifications and a mild physical activity increment resulted in significant improvement of insulin sensitivity and increase in total and free testosterone levels, regardless of the presence of hypogonadism.

Effects of low-dose of niacin associated to simvastatin in the treatment of mixed dyslipidemia Salgad.

AIM: The aim of this study was to evaluate the effects of low-dose niacin extended-release (niacin-ER) combined with simvastatin (SV) in the treatment of patients with mixed dyslipidemia who have not normalized their lipid profile with statin therapy alone. METHODS: A prospective, clinical trial of 35 patients with mixed dyslipidemia who were treated with niacin-ER and SV. The dosage administrated were 250 mg niacin-ER plus 10 mg SV in the first two weeks, 500 mg/20 mg in the next two weeks, and 750 mg/20 mg in the final four weeks. Patients received 200 mg of acetylsalicylic acid 30 minutes before each drug administration. RESULTS: There were significant increases of apolipoprotein A-I and HDL; and decrease of apolipoprotein B, LDL, triglycerides, and total cholesterol. There was low frequency of flushing (10%) and no worsening in the control of fasting and postprandial glycemia and glycated hemoglobin. CONCLUSION: Low-dose niacin-ER associated to simvastatin may be useful for achieving improvement in lipid profile or even to achieve the targets recommended for prevention of cardiovascular disease. Other advantages are the low frequency of flushing, which improved adherence to treatment, and no worsening of insulin resistance in patients with or without diabetes mellitus.

Patients with nephrolithiasis and blood hypertension have higher calciuria than those with isolated nephrolithiasis or hypertension?

AIM: The aim of this study was to determine urinary excretion of calcium, uric acid and sodium and to evaluate insulin resistance in patients with nephrolithiasis and blood hypertension, isolated and in association, and in healthy controls, in absence of obesity and diabetes. METHODS: The study included 83 non-obese or diabetic patients: 17 with nephrolithiasis and hypertension (group D); 25 with nephrolithiasis (group C); 17 with hypertension (group B) and 24 healthy controls (group A). Urinary analysis was done in 24-hour urine collection and insulin resistance was evaluated through the HOMA-IR index. RESULTS: Calciuria was higher in group D in relation to groups A (P<0.01), B (P<0.01) and C (P=0.01). There was no significant difference between groups A and B (P=0.32), A and C (P=0.10) and B and C (P=0.68). Correlation analysis between urinary calcium detected strong correlation with uric acid in group A, regular in groups B and C and, strong with sodium in groups B and C. No differences were detected in uric acid and sodium excretion or insulin resistance among groups. CONCLUSIONS: Patients with blood hypertension and nephrolithiasis present higher calciuria than healthy people, with hypertension or with lithiasis and do not have the positive correlation observed in these latter groups with renal excretion of uric acid and sodium. These results suggest that impaired renal calcium reabsorption in non-obese or diabetic individuals is involved in the association between hypertension and urolithiasis.

Clinical evaluation after 1 year of 153-samarium hydroxyapatite synovectomy in patients with haemophilic arthropathy.

The aim is to evaluate the efficiency of the treatment with 153-samarium hydroxyapatite (153-Sm-HA) in haemophilic arthropathy. Thirty-one patients (30 males) with ages ranging from 8 to 34 years (average age = 20.6 years) were treated with fixed intra-articular dose of 185 MBq (5 mCi) and divided into two groups: infantile-juvenile (13 patients with up to 18 years of age, an average age of 12.7 years and arthropathy evolution of 7.8 years), and adult (18 patients older than 18 years, an average age of 24 years and arthropathy evolution of 18.7 years). The clinical evaluation before and after 1 year of synovectomy used the following criteria: subjective (pain through visual scale, articulation inspection), objective (articular movement through flexion level, sensitivity to palpation and leakage through joint circumference), reduction on the use of the coagulation factor, number of haemarthrosis, and the occurrence of adverse effects. The results were classified as: 1, good (remission from 70% to 100% of manifestations); 2, moderate (remission from 40% to 69%); and 3, poor (remission from 0% to 39%). Seventy-eight joints were tested: 15 knees, 36 elbows, 24 ankles, 1 shoulder and 2 hips. Early scintigraphic (1-2 h) and late scintigraphic (24-72 h) studies were performed after synoviorthesis. The cost of the procedure per joint was also estimated. No significant difference in the synoviorthesis result between groups was observed. The results were good for 75% of elbows, 87.5% of ankles and 40% of knees; the reduction in haemarthrosis and use of the coagulation factor was respectively 78% and 80% for elbows, 82% and 85% for ankles and 30% and 35% for knees. Four cases of reactional synovitis were observed in the 31 patients. The scintigraphic control showed homogeneous distribution of the material with no articular escape. The use of 153 Sm-HA in the treatment of the haemophilic arthropathy is effective for intermediate-size joints (elbows and ankles), but less effective for knees. Moreover, this treatment presents an excellent safety profile and accessible cost.

Internal carotid bifurcation aneurysm in childhood: a case report and literature review.

Childhood aneurysms are rare pathological findings. They present with a low incidence and have characteristic features. When occurred in the first year of life or when giant-sized, survival and recovery may be worst. Nevertheless outcomes are generally better than in adults. A surgical case of an eleven year old boy with excellent outcome is reported, with a subsequent review on the subject. Patients may present with classical subarachnoidal hemorrhage, but also with compressive signs with bigger and unruptured lesions. Initial management of these cases is basically the same of older patients, considering their age, weight and special intensive care for infants. Surgical principles, outcomes and etiology are analyzed.

Diagnosis and management of hyperprolactinemia: results of a Brazilian multicenter study with 1234 patients.

OBJECTIVE: The aim of the study was to evaluate clinical and laboratorial features of 1234 patients with different etiologies of hyperprolactinemia, as well as the response of 388 patients with prolactinomas to dopamine agonists. DESIGN, SETTING, AND PATIENTS: A total of 1234 hyperprolactinemic patients from 10 Brazilian endocrine centers were enrolled in this retrospective study. MAIN OUTCOME MEASURE: PRL measurement, thyroid function tests, and screening for macroprolactin were conducted. RESULTS: Patients were subdivided as follows: 56.2% had prolactinomas, 14.5% drug-induced hyperprolactinemia, 9.3% macroprolactinemia, 6.6% non-functioning pituitary adenomas, 6.3% primary hypothyroidism, 3.6% idiopathic hyperprolactinemia, and 3.2% acromegaly. Clinical manifestations were similar irrespective of the etiology of the hyperprolactinemia. The highest PRL levels were observed in patients with prolactinomas but there was a great overlap in PRL values between all groups. However, PRL>500 ng/ml allowed a clear distinction between prolactinomas and the other etiologies. Cabergoline (CAB) was more effective than bromocriptine (BCR) in normalizing PRL levels (81.9% vs 67.1%, p<0.0001) and in inducing significant tumor shrinkage and complete disappearance of tumor mass. Drug resistance was observed in 10% of patients treated with CAB and in 18.4% of those that used BCR (p=0.0006). Side-effects and intolerance were also more common in BCR treated patients. CONCLUSION: Prolactinomas, drug induced hyperprolactinemia, and macroprolactinemia were the 3 most common causes of hyperprolactinemia. Although PRL levels could not reliably define the etiology of hyperprolactinemia, PRL values >500 ng/ml were exclusively seen in patients with prolactinomas. CAB was significantly more effective than BCR in terms of prolactin normalization, tumor shrinkage, and tolerability.

The role of non-invasive dynamic tests in the diagnosis of Cushing's syndrome.

OBJECTIVE: To evaluate the role of non-invasive dynamic tests in the diagnosis and differential diagnosis of Cushing's syndrome (CS). METHODS: We studied laboratory features of 74 patients with endogenous CS, subdivided as follows: 46 (62.1%) with Cushing's disease (CD), 21 (28.3%) with an adrenal tumor, and 7 (9.5%) with ectopic ACTH syndrome (EAS). RESULTS: In 100% of cases of CS we found serum cortisol levels greater than 1.8 microg/dl after low-dose dexamethasone suppression tests (LDDST), as well as elevation of midnight serum or salivary cortisol. However, urinary free cortisol was normal in 11.5% of patients. ACTH levels were suppressed in patients with adrenal tumors, normal or high in CD and invariably increased in EAS. After the 8-mg overnight dexamethasone suppression test (HDDST), serum cortisol suppression >50% was observed in 79.5% of cases of CD and in 28.6% of subjects with EAS, whereas cortisol suppression >80% was only found in CD. After stimulation with CRH or desmopressin an ACTH rise > or =35% occurred in 86.5% of individuals with CD and 14.3% of those with EAS, whereas an ACTH rise > or =50 achieved 100% specificity. Moreover, the combination of serum cortisol suppression >50% after HDDST and an ACTH increase > or =35% after the administration of CRH or desmopressin only occurred in CD. CONCLUSION: Our findings demonstrate that LDDST had 100% sensitivity for the diagnosis of CS and that HDDST and stimulation tests with CRH or desmopressin may be very useful for confirmation of CS etiology when analyzed together or when more stringent cut-offs are used.

Craniofacial abnormalities, obesity, and hormonal alterations have similar effects in magnitude on the development of nocturnal hypoxemia in patients with acromegaly.

BACKGROUND: In patients with acromegaly, sleep apnea-related hypoxemia results in considerable morbidity and mortality. AIMS: To evaluate the relative weight of pathogenic factors in predicting such hypoxemia. METHODS: In this cross-sectional study, 34 acromegaly patients were submitted to clinical evaluation, nocturnal oximetry, and nasolaryngeal airway tomography. GH, IGF-I, and its upper limit normal value were measured. Nocturnal hypoxemia was defined as >5 episodes of desaturation/h of sleep. Craniofacial abnormalities were expressed using a linear parameter index (LPI). Nocturnal hypoxemia was predicted using logistic regression, including the variables markers of craniofacial abnormality, hormonal alteration, and obesity. Coefficients were standardized in order to determine their effect magnitudes relative to the outcome. The best model included the variables gender, age, LPI, body mass index (BMI), and IGFI upper limit normal value. MAIN RESULTS: In the absence of the age and gender variables, the odds ratio for the LPI (1.60) was slightly higher than those found for BMI (1.49) and upper limit normal value (1.40). When the data were adjusted for age, the hormone upper limit normal value presented little alteration (1.49), although the decrease in the LPI was considerable (1.21), as was the increase in the BMI (2.18). The relative weight of the LPI was age-dependent. The gender variable did not alter the relevance of the others. CONCLUSIONS: The effects that craniofacial aspect, obesity, and hormonal alterations have on nocturnal hypoxemia are of similar magnitude.

Clinical and laboratory features greatly overlap in patients with macroprolactinemia or monomeric hyperprolactinemia.

AIM: The aim of this study was to evaluate the clinical and laboratory features of 64 patients with macroprolactinemia and to compare them to those of individuals with monomeric hyperprolactinemia. METHODS: The study included 64 patients (54 women and 10 men) with macroprolactinemia and 96 patients (70 women and 26 men) with monomeric hyperprolactinemia (32 with prolactinomas). RESULTS: Symptoms related to prolactin (PRL) excess were found in about 44% of individuals from the macroprolactinemia group and in 88.5% of patients with monomeric hyperprolactinemia (P<0.0001). However, the frequency of menstrual disturbances (oligomenorrhea or amenorrhea), galactorrhea and erectile dysfunction did not differ in both groups. In contrast, the association of galactorrhea and menstrual disturbances was significantly more prevalent in women with monomeric hyperprolactinemia. Although mean PRL levels were higher in patients with monomeric hyperprolactinemia (565.9+/-2726.4 vs 113.3+/-94.5 ng/mL, P<0.001), there was a great overlap between both groups. Among macroprolactinemic patients, pituitary magnetic resonance imaging revealed an image suggestive of a microadenoma in 7 (10.9%) and a macroadenoma in 1 (1.6%). Normalization of PRL levels during therapy with dopamine agonists was significantly more frequent in patients with monomeric hyperprolactinemia than in subjects with macroprolactinemia (78.6% vs 32%, P=0.0006). CONCLUSION: Our data show that symptoms related to PRL excess are frequently found in subjects with macroprolactinemia. Moreover, no clinical or laboratory features could reliably differentiate macroprolactinemic patients from those with monomeric hyperprolactinemia. Therefore, the screening for macroprolactin should not be restricted to asymptomatic patients.

Dexamethasone blocks the migration of the human neuroblastoma cell line SK-N-SH.

Glucocorticoids (Gc) influence the differentiation of neural crest-derived cells such as those composing sympathoadrenal tumors like pheochromocytomas, as well as neuroblastomas and gangliomas. In order to obtain further information on the effects of Gc on cells evolving from the neural crest, we have used the human neuroblastoma cell line SK-N-SH to analyze: 1) the presence and the binding characteristics of Gc receptors in these cells, 2) the effect of dexamethasone (Dex) on the migration of SK-N-SH cells, and 3) the effect of Dex on the organization of the cytoskeleton of SK-N-SH cells. We show that: 1) receptors that bind [(3)H]-Dex with high affinity and high capacity (Kd of 9.6 nM, Bmax of 47 fmol/mg cytosolic protein, corresponding to 28,303 sites/cell) are present in cytosolic preparations of SK-N-SH cells, and 2) treatment with Dex (in the range of 10 nM to 1 microM) has an inhibitory effect (from 100% to 74 and 43%, respectively) on the chemotaxis of SK-N-SH cells elicited by fetal bovine serum. This inhibition is completely reversed by the Gc receptor antagonist RU486 (1 microM), and 3) as demonstrated by fluorescent phalloidin-actin detection, the effect of Dex (100 nM) on SK-N-SH cell migration is accompanied by modifications of the cytoskeleton organization that appear with stress fibers. These modifications did not take place in the presence of 1 microM RU486. The present data demonstrate for the first time that Dex affects the migration of neuroblastoma cells as well as their cytoskeleton organization by interacting with specific receptors. These findings provide new insights on the mechanism(s) of action of Gc on cells originating in the neural crest.

Treatment for acute lymphoblastic leukemia in children is associated with papillary carcinoma of thyroid, but not with thyroid disfunction.

AIM: The treatment of acute lymphoblastic leukemia (ALL) in children may cause sequelae, some appearing only at long-term follow-up. We investigated the thyroid gland morphology and the function of the pituitary-thyroid axis in a group of patients treated for ALL in childhood. METHODS: A cohort study was conducted at a tertiary medical center. Thirty-three children (22 males and 11 females; age: 11.9+/-3 years; range: 6 to 18 years) were studied. The mean age at the time of chemotherapy and prophylactic cranial irradiation (12-24 Gy) was 5.5+/-2.6 years (range: 1 to 14 years). The average length of the follow-up was 6.1+/-3 years (range: 2 to 12 years). Thyroid morphology (n=33) was evaluated by palpation and ultrasonography. Thyroid function (n=30) was evaluated measuring total T3 and T4, and by the thyrotrophin-releasing hormone (TRH) test. Prolactin secretion was assessed before and after injection of TRH to evaluate the diagnostic test accuracy. RESULTS: One out of the 33 children (3%) was found to have a papillary carcinoma of thyroid four years after ALL treatment. Thyroid function was normal in all the patients, however one case (3%) showed high TSH (9.2 microU/mL) and prolactin (37.5 ng/mL) basal levels, but normal responses to TRH (TSH = 17.8 microU/mL; prolactin = 82.3 ng/mL). These hormonal alteration were not confirmed at follow-up: TSH = 1.6 microU/mL and prolactin = 13.7 ng/mL. CONCLUSIONS: In this cohort of patients, the treatment of ALL was associated with one case of thyroid carcinoma, but it did not produce adverse effect on the thyroid function, at least after a follow-up lasted on average 6 years.

Dexamethasone blocks the migration of the human neuroblastoma cell line SK-N-SH

Glucocorticoids (Gc) influence the differentiation of neural crest-derived cells such as those composing sympathoadrenal tumors like pheochromocytomas, as well as neuroblastomas and gangliomas. In order to obtain further information on the effects of Gc on cells evolving from the neural crest, we have used the human neuroblastoma cell line SK-N-SH to analyze: 1) the presence and the binding characteristics of Gc receptors in these cells, 2) the effect of dexamethasone (Dex) on the migration of SK-N-SH cells, and 3) the effect of Dex on the organization of the cytoskeleton of SK-N-SH cells. We show that: 1) receptors that bind [³H]-Dex with high affinity and high capacity (Kd of 9.6 nM, Bmax of 47 fmol/mg cytosolic protein, corresponding to 28,303 sites/cell) are present in cytosolic preparations of SK-N-SH cells, and 2) treatment with Dex (in the range of 10 nM to 1 æM) has an inhibitory effect (from 100 percent to 74 and 43 percent, respectively) on the chemotaxis of SK-N-SH cells elicited by fetal bovine serum. This inhibition is completely reversed by the Gc receptor antagonist RU486 (1 æM), and 3) as demonstrated by fluorescent phalloidin-actin detection, the effect of Dex (100 nM) on SK-N-SH cell migration is accompanied by modifications of the cytoskeleton organization that appear with stress fibers. These modifications did not take place in the presence of 1 æM RU486. The present data demonstrate for the first time that Dex affects the migration of neuroblastoma cells as well as their cytoskeleton organization by interacting with specific receptors. These findings provide new insights on the mechanism(s) of action of Gc on cells originating in the neural crest.

Surgical treatment of bilateral multiple intracranial aneurysms. Review of a personal experience in 69 cases.

AIM: There has been much controversy concerning the surgical treatment of bilateral multiple intracranial aneurysms. Some authors advocate the use of two-stage surgery by bilateral pterional craniotomies and others advocate the one stage complete repair of all lesions using the contralateral approach. We analyze the surgical experience of one neurosurgeon using both approaches. METHODS: Sixty nine patients operated on for bilateral multiple intracranial aneurysms were divided in three groups: group A comprised 43 patients (62.3%) in whom all bilateral aneurysms were treated by one stage operation; group B comprised 9 patients (13.0%) in whom the clipping of the contralateral aneurysm it was not possible through the same approach, needing a second operation; group C comprised 17 patients (24.7%) in whom all bilateral multiple intracranial aneurysms were treated by two stage operations. RESULTS: According to the Glasgow Outcome Scale 61 cases (88.4%) had excellent or good results (GOS V, IV), 2 cases (2.9%) had fair results (GOS III) and 6 patients have died (GOS I). The results of group A were significantly better than in-group B (p<0,05 Fisher test), but they were not different in relation to the group C (p=0,439 Fisher test). Among the six deaths, only one was related to the surgical procedure. CONCLUSIONS: Under favorable clinical situations, as patients in H&H I to III, good brain conditions during the surgical procedure and aneurysms smaller than 1,5 cm, the contralateral surgical approach for the treatment of patients with bilateral multiple intracranial aneurysms can be used with advantages over the two stage approach.

Growth hormone provocation tests and their prediction in the growth of children treated for acute lymphoblastic leukemia.

AIM: The aim of this study was to evaluate the positive predictive value of two growth hormone stimulation tests (insulin-induced hypoglycemia and clonidine) for stature below percentile 10 in patients treated for acute lymphoblastic leukemia in childhood. METHODS: The study population was a cohort of 30 patients (aged 14.1+/-2.9 years; 20 male) treated for acute lymphoblastic leukemia during childhood and then examined after insulin-induced hypoglycemia (30 patients) and clonidine (16 patients) tests. The follow-up time was 7.7+/-2.8 years since treatment and 2.3+/-1.3 years after administration of the tests. RESULTS: In the last evaluation, 12 patients (40%) were below and 18 (60%) were above percentile 10. The insulin-induced hypoglycemia test response was: 9 patients (30%) had growth hormone peak <5 ng/mL and 19 (63.3%) <7 ng/mL. The clonidine test response was: 7 patients had growth hormone peak <5 ng/mL and 8 (50%) <7 ng/mL. For stature below of the percentile 10, the positive predictive values of insulin-induced hypoglycemia test (33%) and clonidine (28%) were low when growth hormone peak <5 ng/mL was considered; however, when growth hormone peak <7 ng/mL was considered, the positive predictive values were 83% and 50% for the insulin-induced hypoglycemia and clonidine tests, respectively. CONCLUSIONS: In patients treated for acute lymphoblastic leukemia in childhood, the positive predictive values for statural deficit of both tests were low, except for the insulin-induced hypoglycemia test when a growth hormone peak <7 ng/mL was considered.

Differential diagnosis and treatment of hyponatremia following pituitary surgery.

Hyponatremia is a frequent occurrence after pituitary surgery, having been described in 9% to 35% of the patients. It is produced by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) or, more frequently, by the cerebral salt-wasting syndrome (CSWS). The clinical presentation of both syndromes is identical and the differential diagnosis can be difficult. The determination of the volemic state is essential for the diagnosis, since the patients with the SIADH are euvolemic or hypervolemic, while those with CSWS are hypovolemic. Several methods can be used to detect the volemic state in these patients and, among them, the furosemide test can best discriminate between SIADH and CSWS. A furosemide infusion (20 mg) normalizes sodium serum levels in SIADH patients, but not in CSWS patients who remain hyponatremic. The differentiation between the 2 syndromes is clinically relevant since their treatment is antithetical. SIADH patients need liquid restriction of liquids and/or furosemide to reduce the volume of extracellular water, while CSWS patients need volume replacement with sodium supplementation (or fludrocortisone can be a good alternative). The diagnosis and treatment of these syndromes are discussed on the basis of the literature reports.