Neuroendocrine predictors of vasoplegia after cardiopulmonary bypass.

PURPOSE: Vasoplegia often complicates on-pump cardiac surgery. Systemic inflammatory response induced by extracorporeal circulation represents the major determinant, but adrenal insufficiency and postoperative vasopressin deficiency may have a role. Pathophysiological meaning of perioperative changes in endocrine markers of hydro-electrolyte balance has not still fully elucidated. Objectives of the present research study were to estimate the incidence of vasoplegia in a homogeneous cohort of not severe cardiopathic patients, to define the role of presurgical adrenal insufficiency, to evaluate copeptin and NT-proBNP trends in the perioperative. METHODS: We conducted a prospective cohort study in the cardiac intensive care unit of a tertiary referral center. We evaluated 350 consecutive patients scheduled for cardiac surgery; 55 subjects completed the study. Both standard and low-dose corticotropin stimulation tests were performed in the preoperative; copeptin and NT-proBNP were evaluated in the preoperative (T0), on day 1 (T1) and day 7 (T2) after surgery. RESULTS: Nine subjects (16.3%) developed vasoplegic syndrome with longer bypass and clamping time (p < 0.001). Reduced response to low-dose ACTH test was not associated to vasoplegia. Preoperative copeptin > 16.9 pmol/L accurately predicted the syndrome (AUC 0.86, 95% CI 0.73-0.94; OR 1.17, 95% CI 1.04-1.32). An evident correlation was observed at 7 days postoperative between NT-proBNP and copeptin (r 0.88, 95% CI 0.8-0.93; p < 0.001). CONCLUSION: Preoperative impaired response to low-dose ACTH stimulation test is not a risk factor for post-cardiotomic vasoplegia; conversely, higher preoperative copeptin predicts the complication. On-pump cardiac surgery could be an interesting model of rapid heart failure progression.

Reference ranges of late-night salivary cortisol and cortisone measured by LC-MS/MS and accuracy for the diagnosis of Cushing's syndrome.

PURPOSE: International guidelines recommend salivary cortisol for the diagnosis of Cushing's syndrome. Despite mass spectrometry-based assays are considered the analytical gold-standard, there is still the need to define reference intervals and diagnostic accuracy of such methodology. METHODS: 100 healthy volunteers and 50 consecutive patients were enrolled to compare LC-MS/MS and electrochemiluminescence assay for the determination of late-night salivary cortisol and cortisone. Moreover, we aimed to determine reference intervals of salivary steroids in a population of healthy individuals and diagnostic accuracy in patients with suspected hypercortisolism and in a population including also healthy individuals. RESULTS: Method comparison highlighted a positive bias (51.8%) of immunoassay over LC-MS/MS. Reference intervals of salivary cortisol (0.17-0.97 µg/L), cortisone (0.84-4.85 µg/L) and ratio (0.08-0.30) were obtained. The most accurate thresholds of salivary cortisol for the diagnosis of hypercortisolism were 1.15 µg/L in the population with suspected hypercortisolism (AUC 1) and 1.30 µg/L in the population including also healthy individuals (AUC 1). Cut-off values of salivary cortisone (7.23 µg/L; Se 92.9%, Sp 97.2%, AUC 0.960 and Se 92.9%, Sp 99.1%, AUC 0.985 in suspected hypercortisolism and in overall population, respectively) and cortisol-to-cortisone ratio (0.20; Se 85.7%, Sp 80.6%, AUC 0.820 and Se 85.7%, Sp 85.5%, AUC 0.855 in suspected hypercortisolism and in overall population, respectively) were accurate and similar in both populations. CONCLUSION: LC-MS/MS is the most accurate analytical platform for measuring salivary steroids. Obtained reference intervals are coherent with previously published data and diagnostic accuracy for diagnosis of overt hypercortisolism proved highly satisfactory.

The ghrelin gene products and exendin-4 promote survival of human pancreatic islet endothelial cells in hyperglycaemic conditions, through phosphoinositide 3-kinase/Akt, extracellular signal-related kinase (ERK)1/2 and cAMP/protein kinase A (PKA) signalling pathways.

AIMS/HYPOTHESIS: Pancreatic islet microendothelium exhibits unique features in interdependent relationship with beta cells. Gastrointestinal products of the ghrelin gene, acylated ghrelin (AG), unacylated ghrelin (UAG) and obestatin (Ob), and the incretin, glucagon-like peptide-1 (GLP-1), prevent apoptosis of pancreatic beta cells. We investigated whether the ghrelin gene products and the GLP-1 receptor agonist exendin-4 (Ex-4) display survival effects in human pancreatic islet microendothelial cells (MECs) exposed to chronic hyperglycaemia. METHODS: Islet MECs were cultured in high glucose concentration and treated with AG, UAG, Ob or Ex-4. Apoptosis was assessed by DNA fragmentation, Hoechst staining of the nuclei and caspase-3 activity. Western blot analyses and pharmacological inhibition of protein kinase B (Akt) and extracellular signal-related kinase (ERK)1/2 pathways, detection of intracellular cAMP levels and blockade of adenylyl cyclase (AC)/cAMP/protein kinase A (PKA) signalling were performed. Levels of NO, IL-1ß and vascular endothelial growth factor (VEGF)-A in cell culture supernatant fractions were measured. RESULTS: Islet MECs express the ghrelin receptor GHS-R1A as well as GLP-1R. Treatment with AG, UAG, Ob and Ex-4 promoted cell survival and significantly inhibited glucose-induced apoptosis, through activation of PI3K/Akt, ERK1/2 phosphorylation and intracellular cAMP increase. Moreover, peptides upregulated B cell lymphoma 2 (BCL-2) and downregulated BCL-2-associated X protein (BAX) and CD40 ligand (CD40L) production, and significantly reduced the secretion of NO, IL-1ß and VEGF-A. CONCLUSIONS/INTERPRETATION: The ghrelin gene-derived peptides and Ex-4 exert cytoprotective effects in islet MECs. The anti-apoptotic effects involve phosphoinositide 3-kinase (PI3K)/Akt, ERK1/2 and cAMP/PKA pathways. These peptides could therefore represent a potential tool to improve islet vascularisation and, indirectly, islet cell function.

Circulating obestatin levels in normal and Type 2 diabetic subjects.

BACKGROUND: Obestatin has been discovered as a new product of the ghrelin gene. Its physiological actions are still a matter of debate, but it seems that this peptide is likely to be involved in the control of insulin secretion and action as well as of adipocyte function. It has been already shown that obestatin secretion in humans is negatively modulated by food intake. AIM: To clarify obestatin secretion in normal subjects and in patients with Type 2 diabetes (T2D) in basal conditions and after a standardized meal. SUBJECTS/METHODS: Five normal subjects and 5 T2D patients were studied during infusion of saline (iv for over 5 h from -120 to +180 min). A standardized lunch was served at 0 min. Obestatin, glucose, and insulin levels were assayed at -120, -90, -60, -45, -30, -15, 0, 15, 30, 45, 60, 90, 120, 150, and 180 min. RESULTS: From -120 to 0 min, obestatin levels in normal and T2D subjects were similar (area under the curve: 32.3+/-5.6 pg/ml/min vs 31.1+/-1.0 pg/ml/min). After the meal, circulating obestatin levels underwent a clear decrease in normal subjects (0 min: 300.6+/-34.7 pg/ml vs nadir at 60 min: 161.8+/-29.4 pg/ml; p=0.002) but not in diabetic patients (0 min: 267.2+/-16.5 pg/ml vs nadir at 180 min: 226.0+/-10.5 pg/ml). CONCLUSION: This study shows that normal and diabetic subjects display similar levels of circulating obestatin in fasting condition. However patients with T2D look refractory to the inhibitory effect of meal on obestatin secretion.

Insulin-like growth factor binding protein-3 induces angiogenesis through IGF-I- and SphK1-dependent mechanisms.

Angiogenesis is critical for development and repair, and is a prominent feature of many pathological conditions. Based on evidence that insulin-like growth factor binding protein (IGFBP)-3 enhances cell motility and activates sphingosine kinase (SphK) in human endothelial cells, we have investigated whether IGFBP-3 plays a role in promoting angiogenesis. IGFBP-3 potently induced network formation by human endothelial cells on Matrigel. Moreover, it up-regulated proangiogenic genes, such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2 and -9. IGFBP-3 even induced membrane-type 1 MMP (MT1-MMP), which regulates MMP-2 activation. Decreasing SphK1 expression by small interfering RNA (siRNA), blocked IGFBP-3-induced network formation and inhibited VEGF, MT1-MMP but not IGF-I up-regulation. IGF-I activated SphK, leading to sphingosine-1-phosphate (S1P) formation. The IGF-I effect on SphK activity was blocked by specific inhibitors of IGF-IR, PI3K/Akt and ERK1/2 phosphorylation. The disruption of IGF-I signaling prevented the IGFBP-3 effect on tube formation, SphK activity and VEGF release. Blocking ERK1/2 signaling caused the loss of SphK activation and VEGF and IGF-I up-regulation. Finally, IGFBP-3 dose-dependently stimulated neovessel formation into subcutaneous implants of Matrigel in vivo. Thus, IGFBP-3 positively regulates angiogenesis through involvement of IGF-IR signaling and subsequent SphK/S1P activation.

Unacylated as well as acylated ghrelin promotes cell survival and inhibit apoptosis in HIT-T15 pancreatic beta-cells.

Ghrelin is mainly produced by the stomach, although it is expressed in other tissues, including the pancreas. Among its pleiotropic actions, ghrelin prevents the development of diabetes in rats and exerts mitogenic and antiapoptotic effects in different cell types. In addition, a ghrelin-producing epsilon-cell population has been demonstrated in rodent islets, suggesting a direct role in the control of islet cell survival. In this study, we investigated the effect of acylated ghrelin (AG) and unacylated ghrelin (UAG) on cell survival of HIT-T15 pancreatic beta cells. We show that both AG and UAG equally prevented beta cell death induced by serum withdrawal. In addition, both peptides inhibited serum starvation-induced apoptosis. These findings indicate that UAG and AG prevent cell death and apoptosis of pancreatic beta cells. Since only AG, but not UAG, binds the GRLN receptor, a different and as yet unknown receptor is likely involved in these survival mechanisms.

What is the effect of dizziness on the quality of life for patients with Meniere's disease?

OBJECTIVE: To evaluate the impact of dizziness on quality of life (QOL) in Meniere's disease (MD) patients. METHODS OF STUDY: Fifty definite MD patients were submitted to the Dizziness Handicap Inventory (DHI), in and out of crisis. The DHI scores were correlated to age, sex, race, disease duration, unilateral/bilateral labyrinth involvement, duration/frequency of vertigo attacks, vestibular and auditory function, aural fullness, tinnitus, imbalance and functional disabilities. Statistical analysis was performed by ANOVA. RESULTS: During crisis, all DHI aspects scores were statistically higher (p < 0.001) than out of crisis. Out of crisis, a statistically significant correlation was found between physical, functional and total scores and bilateral involvement. CONCLUSIONS: QOL impairment is worse during a Meniere's crisis. Out of crisis, QOL impairment is greater in patients with bilateral involvement.

Management of tarsal tunnel syndrome. Report of seven cases.

Seven patients with clinical and electroneurographic evidence of tarsal tunnel syndrome were managed surgically, after failed attempts for non-surgical treatment. Post-operative results were more satisfactory than the previous responses to non-surgical therapies. Tarsal tunnel syndrome appears to respond better to surgical intervention than to conservative management.

[Tarsal tunnel syndrome: report of 11 cases]. / Síndrome do túnel do tarso: relato de 11 casos.

UNLABELLED: Little is know on tarsal tunnel syndrome by means of image and electrophysiological access. It is imperative the differential diagnosis on diseases which present foot pain. PURPOSE: To present patients with foot pain complaints, whose clinical pattern allowed the diagnosis of tarsal tunnel syndrome. METHODS: Eleven patients underwent nerve velocity conduction examination concluding for entrapment. They were submitted to tarsal tunnel surgical decompression by sectioning the flexor retinaculum. RESULTS: Most of the cases showed a marked fibrous thickening. The improvement of symptoms was noted in the first weeks. No recurrence was observed from three months to five years. CONCLUSION: The main question was the presentation of the tarsal tunnel syndrome and some adequate procedures.

[Early diagnosis of Fabry disease in children]. / Diagnosi precoce di malattia di Fabry in età pediatrica.

Fabry disease, a rare X-linked lysosomal storage disorder, is caused by deficiency of the enzyme α-galactosidase A. The incidence, ranging from one over 40 000 to one over 11 7000 worldwide is probably underestimated due to its unspecific pattern of presentation. The symptoms, including neurological, gastrointestinal, renal, ophthalmological and dermatologic manifestations, start in childhood and adolescence, cause a significant morbidity and are likely to affect the patient's quality of life. Furthermore, Anderson-Fabry disease always progress leading to a multiorgan dysfunction and life-threatening complications with end-stage renal disease, cardiomyopathy and high incidence of stroke. The estimated life in untreated patients is reduced by 15-20 years respectively in men and women. The enzyme replacement therapy, available in Europe from 2001, results in a reduction of major organs failure, morbidity and mortality. We present the case of an 8-year-old male admitted to our Division for overweight with a previous history of acroparesthesias, severe acute pain in hands and feet, abdominal pain, diarrhoea, constipation, bitemporal headache, dyshidrosis, recurrent fever, exercise intolerance and reduced quality of life. The physical examination was within normal limits. The α-galactosidase A activity was deficient in plasma and normal in peripheral leukocytes; the GLA gene showed a nucleotide substitution c.352C>T (p.Arg 118 Cys) in the eson 2 with a residual enzyme activity of the 29% suggesting the diagnosis of Fabry disease. Blood and urine chemistry, the slit-lamp examination and MRI of kidneys, heart and brain excluded any major organ involvement. The enzyme replacement therapy was then started almost three months ago using agasidase alfa at a dose of 0.2 mg/kg infused intravenously every two weeks but, unfortunately, no relief in the symptoms have been reported so far without any severe adverse reactions. This case report aims to point out the importance of an early diagnosis in order to prevent the progression of the disease, the multiorgan failure and to improve the long-term prognosis.

H9c2 cardiac muscle cells express all somatostatin receptor subtypes.

The aim of the present study was to verify the hypothesis that SS receptor subtypes (SSTRs) are expressed by H9c2 cardiac muscle cells. SSTRs expression was investigated by RT-PCR and Western blot analysis at both mRNA and protein level. Our findings demonstrate that H9c2 cells express all SSTR subtypes I-5 (SSTRI-5) at the mRNA and protein level. Thus, H9c2 cells would represent a new model to study the direct biological activities of SS and its analogues at the cardiac level.

Epidermoid tumour of the posterior fossa causing multiple facial pain--a case report.

A 53-year-old woman presented with three types of pain. The pains had characteristics of neuralgia of the fifth cranial nerve, ninth cranial nerve, and cluster headache. On further investigation, a tumour in the posterior fossa was observed and histologically shown to be an epidermoid tumour.

Metastase medular tardia de germinoma supra-selar. / Late medullary metastasis of suprasellar germinoma: report of a case

Paciente operado de tumor intramedular que evoluiu para o obito, cuja necropsia revelou presenca de germinoma intramedular e germinoma supra-selar remanescente de tratamento cirurgico e radioterapico realizado 11 anos antes. Sao discutidas a etiologia e a conduta cirurgica e radioterapica

Sindrome de emaciacao diencefalica associada a presenca de craniofaringioma

Os autores apresentam um caso de sindrome de emaciacao diencefalica associada a presenca de craniofaringioma. O paciente, de sete anos de idade, apresentava emagrecimento profundo, baixa estatura, palidez cutanea e papiledema bilateral. Pela revisao efetuada da literatura, esta sindrome, tambem conhecida como de Russel, ainda nao havia sido relatada em crianca em associacao com este tipo de tumor.

Disseminated form of an intracranial germinoma: report of one case

The authors report a case of a suprasellar germinoma with a diffusely involvement of the ventricular system. The proper diagnostic and therapeutic procedures for the management of this lesion are also discussed.

Avaliacao quantitativa do nistagmo optoninetico horizontal e vertical normal. / Quantitative evaluation of normal horizontal and vertical optocynetic nystagmus

As caracteristicas quantitativas da ocorrencia do nistagmo optocinetico horizontal e vertical foram analisadas, em 39 indivuduos normais, a luz da vecto-electronistagmografia. O nistagmo optocinetico horizontal e vertical foram relativamente simetrico nas duas direcoes de rotacao do estimulador optocinetico, sendo o valor limite normal da preponderancia direcional igual a 0,57 e 0,85 respectivamente

Síndrome do túnel do tarso: relato de 11 casos / Tarsal tunnel syndrome: report of 11 cases

Na atualidade, apesar de pouco conhecida, a síndrome do túnel do tarso, pelos recursos eletroneurofisiológicos e de imagem, se impoe no diagnóstico diferencial das patologias que determinem sintomas álgicos nos pés. Objetivo. Sao apresentados e discutidos pacientes com queixa de dor nos pés cujo quadro clínico permitiu o diagnóstico de síndrome do túnel do tarso. MÉTODOS. Onze pacientes foram submetidos e exame eletroneuromiográfico conclusivo de compressao nervosa e, em seguida, foram submetidos a cirurgia específica, quando foi feita a descompressao do túnel do tarso pela secçao do retináculo dos flexores. Resultados. Nos casos apresentados, importante espessamento fibroso foi observado na maioria dos casos, e a melhora da sintomatologia dolorosa foi verificada nas primeiras semanas do pós-operatório, sendo os pacientes observados por intervalo de 3 meses a 5 anos, nao apresentando recorrência do quadro de dor.