Intersubject variability of blood analysis reference values: assessment of age and locality influence by means of a linear discriminant analysis model.

Glycemic and lipidic profiles might be influenced by several factors. The influence of the age group in the most extensively evaluated lipidic and glycemic parameters is more or less well-accepted. To verify this empirical notion, 996 human subjects aged between 21 and 90 years from different localities were characterized according to age. To assess lipid profile, total cholesterol and cholesterol associated with lipoprotein fractions (low-density lipoprotein cholesterol and high-density lipoprotein cholesterol) and triglycerides were determined. Regarding glycemic profile, glucose, and glycated hemoglobin were measured. The majority of the population had values of lipidic parameters fit into the reference values, presenting low or moderate risk for developing cardiovascular disease. Blood glucose was often far above the desirable, but this can be devalued due to the HbA1c values, which were overwhelmingly located in the normal range. The categorization of data in different age groups did not allow defining statistically significant differences. Despite the discriminant linear model was presented, the results indicate that age group did not act as a strong discriminant factor. Somehow unexpectedly, the most significant differences were found among the different localities, which tended to show a similarity according with their latitude. Furthermore, there were no significant correlations in the parameters associated with lipidic profile, but there was a direct correlation between glucose levels and HbA1c (glycemic parameters).

Breast carcinomas with hyperprolactinemia at the time of diagnosis-clinico-biological association.

AIM: To analyse association between preoperative hyperprolactinemia serum levels and clinical and biological features of breast tumors. METHODS: Serum levels of prolactin were measured in 253 women with invasive breast cancer. Clinical and biological parameters analysed were age, size, lymph node involvement, distant metastasis and immunohistochemical expression of estrogen receptor, progesterone receptor, androgen receptor, bcl-2, p53 and Ki67. RESULTS: In ductal carcinomas hyperprolactinemia were associated with high age (p = 0.017), and with bcl-2 + + + expression (p = 0.017). Furthermore, serum prolactin values were significantly higher in bcl-2 +++ cases vs negative (p = 0.029); the same happened when we considered the positivity threshold of 25 ng/mL (p = 0.015). CONCLUSION: Is possible to detect in 6% of infiltrating ductal breast carcinomas hyperprolactinemia (>25 ng/mL), being associated only with increasing age, but not with other clinical or biological factors; and 2) the most surprising data was the association between prolactinemia (qualitative (>25 ng/mL) and quantitative) and intense bcl-2 tissue expression, which suggests that, probably, this (prolactinemia) is not a sign of worse prognosis and evolution.

[The immunohistochemical expression of cyclooxygenase 2 is inversely associated with (18)F-FDG-PET SUV values in non-small-cell lung cancers. Initial results]. / La expresión inmunohistoquímica intensa de ciclooxigenasa 2 se asocia inversamente con los valores máximos de SUV en la (18)F-FDG-PET de pacientes afectados de carcinomas no microcíticos de pulmón. Relación con otros factores biológicos.

OBJECTIVE: To study the expression of COX-2 and its possible relationship with the maximum standardized uptake value (SUV) in FDG-PET, and EGFR, p16 and MIB1 expression in patients with NSCLC. MATERIAL AND METHOD: 45 patients (12 adenocarcinomas and 33 squamous cell carcinomas) were included in this study; the immunohistochemical expression of COX-2, MIB-1, p16 and EGFR was determined using tissue-array. Each PET was performed 60 minutes after the i.v. administration of 350-518 MBq of FDG on an Advance system (GE) in 2D acquisition mode. RESULTS: COX-2 expression was detected in 35 out of 45 cases, and was very significant (> ++) in 12 of them. SUV values were lower in the COX-2 > ++ cases that in the remaining cases (13.4 +/- 1.2 vs. 12.9 vs. 17.1 +/- 1.5; p = 0.059). COX-2 > ++ expression and maxSUV values were not correlated with the clinical stage. The expression of COX-2 > ++ was correlated positively with p16 (r = 0.36; p = 0.014) and negatively with MIB1 (r = -0.32; p = 0.041) expression, whereas the SUV was correlated positively with EGFR (r = 0.44; p = 0.004) and negatively with p16 (r = -0.29; p = 0.041) expression. CONCLUSIONS: Our results suggest that: a) the expression of COX-2 > ++ is often found in this kind of lung cancer and is not associated with the clinical stage; b) the maxSUVs were not related to the stage and were lower in COX-2 > ++ tumours than in the other cases; and c) the different behaviour of both parameters can be explained by their correlation with cell proliferation (MIB1), EGFR and p16 expression.

Papillary thyroid carcinoma after recombinant GH therapy for Turner syndrome.

Turner syndrome (TS) has been included for several years among the indications for GH treatment, generally with satisfactory outcomes. Nevertheless, the long-term effects of this treatment in non-GH deficient patients are not fully known. The incidence of thyroid carcinoma is rare in patients during childhood, it is unusual to find this neoplasia in children under sixteen years old. This article reports the cases of two Spanish patients with papillary thyroid carcinoma after GH treatment for TS. Recent studies have indicated a possible relationship between the GH-IGF axis and the pathogenesis of neoplasias, questioning the chance association of these two pathologies. In line with this, we detected GH receptor expression in the papillary carcinoma cells. Long-term prospective studies are required to clarify the possible effects of GH treatment on the risk of neoplasia.

Endocrine disruptors.

Man does not come into the world pre-determined. The lifetime set of environmental conditions impinging on a given individual has been termed the ambiome, which together with the genome and the proteome determines each individual's development and construction. Among the most important elements making up the ambiome are endocrine disruptors. An endocrine disruptor is a chemical substance that has adverse effects on an organism or its progeny, through the endocrine system. The number of known endocrine disruptors is large and continuously increasing, and includes both naturally occurring and synthetic substances. We are convinced that they entail genuine problems; although it is difficult to assess their magnitude and real significance, and we will certainly need some time, probably several decades, to obtain conclusive results; but even so, we consider that the existing body of evidence about effects of endocrine disruptors on human health is sufficiently worrying to justify precautionary measures.

Association of Factor V Secretion with Protein Kinase B Signaling in Platelets from Horses with Atypical Equine Thrombasthenia.

BACKGROUND: Two congenital bleeding diatheses have been identified in Thoroughbred horses: Glanzmann thrombasthenia (GT) and a second, novel diathesis associated with abnormal platelet function in response to collagen and thrombin stimulation. HYPOTHESIS/OBJECTIVES: Platelet dysfunction in horses with this second thrombasthenia results from a secretory defect. ANIMALS: Two affected and 6 clinically normal horses. METHODS: Ex vivo study. Washed platelets were examined for (1) expression of the αIIb-ß3 integrin; (2) fibrinogen binding capacity in response to ADP and thrombin; (3) secretion of dense and α-granules; (4) activation of the mammalian target of rapamycin (mTOR)-protein kinase B (AKT) signaling pathway; and (5) cellular distribution of phosphatidylinositol-4-phosphate-3-kinase, class 2B (PIK3C2B) and SH2 containing inositol-5'-phosphatase 1 (SHIP1). RESULTS: Platelets from affected horses expressed normal amounts of αIIb-ß3 integrin and bound fibrinogen normally in response to ADP, but bound 80% less fibrinogen in response to thrombin. α-granules only released 50% as much Factor V as control platelets, but dense granules released their contents normally. Protein kinase B (AKT) phosphorylation was reduced after thrombin activation, but mTOR Complex 2 (mTORC2) and phosphoinositide-dependent kinase 1 (PDK1) signaling were normal. SH2-containing inositol-5'-phosphatase 1 (SHIP1) did not localize to the cytoskeleton of affected platelets and was decreased overall consistent with reduced AKT phosphorylation. CONCLUSIONS AND CLINICAL SIGNIFICANCE: Defects in fibrinogen binding, granule secretion, and signal transduction are unique to this thrombasthenia, which we designate as atypical equine thrombasthenia.

Effect of growth hormone (GH)-releasing hormone (GHRH), atropine, pyridostigmine, or hypoglycemia on GHRP-6-induced GH secretion in man.

His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To further characterize the effects and mechanism of action of GHRP-6 on GH secretion, we assessed in normal man plasma GH responses to that hexapeptide 1) alone and in combination with exogenous GH-releasing hormone (GHRH) administration, 2) in a state of high endogenous somatostatinergic tone after atropine administration, and 3) in a state of low endogenous somatostatinergic tone induced by the cholinergic receptor agonist drug pyridostigmine or after insulin-induced hypoglycemia. We found a similar increase in plasma GH levels after the administration of either GHRP-6 (1 microgram/kg) or GHRH (1 microgram/kg); the areas under the curve (AUC) were (mean +/- SEM) 973 +/- 181 and 821 +/- 139, respectively. After combined GHRP-6 and GHRH administration, GH responses were considerably greater than those after either compound alone (4412 +/- 842; P < 0.01). Administration of the cholinergic receptor antagonist atropine (1 mg, im) completely prevented the GH responses to GHRP-6 (area under the curve, 103 +/- 14 vs. 815 +/- 156, respectively). On the other hand, pyridostigmine, a cholinergic agonist, slightly increased GH responses to GHRP-6 (P < 0.01 when comparing the AUC after pyridostigmine administration of 1571 +/- 151 and the AUC after administration of GHRP-6 alone of 815 +/- 156). Finally, combined GHRP-6 and insulin administration induced a much greater increase in plasma GH levels (AUC, 4047 +/- 327) than insulin alone (1747 +/- 229; P < 0.05) or GHRP-6 alone (1248 +/- 376; P < 0.05). Our results lend support to the view that GHRP-6-induced GH secretion is exerted through a non-GHRH-dependent mechanism. Furthermore, the fact that enhancement of somatostatinergic tone with atropine completely prevented the GH responses to GHRP-6, while pyridostigmine and insulin-induced hypoglycemia, which increased plasma GH levels by inhibiting hypothalamic somatostatin release, increased the same response suggest that although GHRP-6-induced GH secretion is dependent on the endogenous somatostatinergic tone, the stimulatory effect of GHRP-6 on plasma GH levels is not mediated by a change in hypothalamic somatostatinergic tone.

Role of the serotonin receptor subtype 5-HT1D on basal and stimulated growth hormone secretion.

At present, four main types of serotonin (5-HT) receptors have been identified in the brain (5-HT1, 5-HT2, 5-HT3, and 5-HT4). In addition, the 5-HT1 have been further subclassified. We have taken advantage of a new selective 5-HT1D receptor agonist 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide succinate, Sumatriptan, to evaluate the role of 5-HT1D receptors on GH secretion. To this end, several tests with or without sumatriptan were undertaken in normal prepubertal children. Furthermore, we assessed the effect of Sumatriptan on basal GH secretion and the GH response to GHRH in obese children. In normal children, Sumatriptan administration (3 mg, sc) resulted in an increase in basal GH levels at 30 min (7.7 +/- 1.5 micrograms/L; P < 0.05) and increased GH responses to GHRH (47.3 +/- 6.4 vs. 29.6 +/- 9.7 micrograms/L; P < 0.05). The Sumatriptan-induced increase in GH responses to GHRH was dependent on the stimulus tested. Pretreatment with Sumatriptan did not modify the GH response to clonidine or pyridostigmine, as assessed by the peak GH response and the area under the curve. In contrast, it increased the GH response to arginine. In the obese subjects, the GH response to GHRH was reduced (7.3 +/- 1.0 vs. 29.6 +/- 9.7 micrograms/L at 30 min) compared to that in control children (P < 0.05). Sumatriptan administration did not alter the basal GH value (peak GH, 1.7 +/- 0.3 micrograms/L at 30 min). However, Sumatriptan administration clearly increased the effect of GHRH, resulting in a GH peak of 14.6 +/- 3.1 micrograms/L at 30 min (P < 0.01). To assess the specificity of Sumatriptan on anterior pituitary hormone secretion, we studied its effect on TSH and PRL responses to TRH as well as LH-releasing hormone-induced LH and FSH secretion. Administration of Sumatriptan did not alter the response of any of these hormones. Our results indicate that 5-HT1D receptors have a stimulatory effect on GH secretion, possibly by inhibiting hypothalamic somatostatin release.

Absence of growth hormone (GH) secretion after the administration of either GH-releasing hormone (GHRH), GH-releasing peptide (GHRP-6), or GHRH plus GHRP-6 in children with neonatal pituitary stalk transection.

GH-releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic compound that releases GH in a specific and dose-related manner through mechanisms and a point of action that are mostly unknown, but different from those of GHRH. In man, GHRP-6 is more efficacious than GHRH, and a striking synergistic action occurs when both compounds are administered together. To explain such a synergistic effect, it has been postulated, but not proven, that GHRP-6 acts through a double mechanism, with actions exerted at the pituitary and the hypothalamic level. On the other hand, patients with the syndrome of GH deficiency due to perinatal pituitary stalk transection have any hypothalamic factor nonoperandi. The aim of the present study was 3-fold: 1) to further understand how relevant, if at all, the hypothalamic action of GHRP-6 is for GH regulation; 2) to evaluate whether GHRP-6 plus GHRH could be a suitable diagnostic tool in children with pituitary stalk transection; and 3) to compare these results with similar published studies performed in patients with hypothalamo-pituitary disconnection, who developed the disease as adults. Seven patients with GH deficiency and different degrees of panhypopituitarism due to perinatal pituitary stalk transection and 7 age- and sex-matched normal controls were studied. The subjects underwent 3 different tests on separate occasions, being challenged with GHRH (1 microgram/kg, iv), GHRP-6 (1 microgram/kg, iv), or GHRH plus GHRP-6. GH was analyzed as the area under the curve (mean +/- SE; micrograms per L/90 min). In normal subjects, GH secretion was 1029 +/- 202 after GHRH treatment, 1221 +/- 345 after GHRP-6, and 3542 +/- 650 after GHRH plus GHRP-6; the latter value was significantly (P < 0.05) higher than the secretion elicited by GHRH or GHRP-6 alone. In the group of patients with perinatal pituitary stalk transection, the level of GH after GHRH treatment was 116 +/- 22 and was even more reduced (P < 0.05) after GHRP-6 treatment (37 +/- 8). After GHRH plus GHRP-6, GH secretion in those patients was 177 +/- 27, significantly higher (P < 0.05) than the secretion induced by either GHRH or GHRP-6 alone. Individually examined, none of the patients tested with the most potent stimulus known to date (GHRH plus GHRP-6) exhibited GH secretion greater than 5 micrograms/L.(ABSTRACT TRUNCATED AT 400 WORDS)

Nocturnal rise of leptin in normal prepubertal and pubertal children and in patients with perinatal stalk-transection syndrome.

We studied 24-h profiles of circulating leptin levels using a sensitive and specific radioimmunoassay in healthy pre- (Tanner 1) and pubertal boys and girls (Tanner 3-4) as well as in a group of patients with perinatal stalk-transection syndrome. Similar nyctohemeral rhythm in serum leptin levels were found in prepubertal (MESOR: 2.34 +/- 0.2 ng/ml; amplitude 0.32 +/- 0.1 ng/ml) and pubertal boys (MESOR 2.2 +/- 0.2 ng/ml; amplitude 0.38 +/- 0.07 ng/ml). Likewise, no differences were found between prepubertal (MESOR 6.6 +/- 1.07 ng/ml; amplitude 1.67 +/- 0.4 ng/ml) and pubertal girls (MESOR 4.05 +/- 0.5 ng/ml; amplitude 0.95 +/- 0.2 ng/ml). In contrast, higher MESOR (p < 0.002) and amplitude values (p < 0.005) were found in prepubertal and pubertal girls than in prepubertal and pubertal boys. Finally a significant nyctohemeral rhythm in serum leptin levels was found in patients with perinatal stalk-transection syndrome (MESOR: 9.3 +/- 2.3 ng/ml; amplitude 1.46 +/- 0.4 ng/ml). This data shows the existence of sexual dimorphism in the nyctohemeral rhythm in serum leptin levels that are not influenced by the pubertal stage or by pulsatile anterior pituitary hormone secretion.

Role of the new growth hormone-releasing secretagogues in the diagnosis of some hypothalamopituitary pathologies.

Growth hormone (GH)-releasing hormone (GHRH) and somatostatin have a dominant role in regulating GH secretion. However, results of studies using the new class of GH secretogogues, particularly GHRP-6, indicate that there may also be other, as yet undefined, hypothalamic mechanisms involved. Studies in adults with hypothalamopituitary disconnection (functional pituitary stalk transection), show GHRP-6-mediated GH release to be completely blocked, indicating a main action at the hypothalamic rather than the pituitary level. The synergistic effect of GHRH plus GHRP-6 administration on GH release seen in normal adults (and virtually unaffected by age, obesity, or sex) is also absent in these patients, providing further support for this conclusion. Studies of the effects of GHRP-6 in children with GH deficiency due to perinatal pituitary stalk transection have produced similar findings. It is suggested that the combined GHRH plus GHRH-6 test should be a promising tool for diagnosing GH deficiency states in both children and adults, and may identify a subgroup of patients with GH deficiency caused by interruption of the hypothalamopituitary connection.

Mycobacterium fortuitum complex endocarditis-case report and literature review.

Endocarditis due to Mycobacterium fortuitum complex is a rare entity generally linked to the hospital environment. Only 18 cases have been published since 1966. Here we present a case of a female who developed an endocarditis due to Mycobacterium chelonae after valve replacement as well as a review of the literature. The course of this kind of endocarditis is generally subacute and the outcome is usually fatal. Blood cultures were positive in 75% of cases of metallic valve endocarditis, versus 20% in bioprostheses. The treatment must include antibiotics that have shown activity against these mycobacteria, such as amikacin, imipenem, cefoxitin, fluorinated quinolones and macrolides (especially clarithromycin). Surgical removal is recommended. Although the prognosis for the patient is poor, we should expect better outcomes with the use of new antibiotic regimens.

Therapeutic optimization of growth hormone deficiency in children and adolescents.

More than 40 years after the introduction of growth hormone (GH) treatment, many questions remain unanswered. Clearly, with the availability of rhGH and with current treatment protocols, treatment efficacy has improved. However, it still remains unclear whether current treatment protocols are the best possible. Before GH deficiency was recognized as a chronic disease, children only received treatment until normal adult height had been reached. However, it has recently been shown that not all GH-dependent body structures and functions normalize in parallel with height. Furthermore, in adolescents with GH deficiency, the interruption of GH substitution leads to severe hormone deficiency symptoms in adulthood. In the case of an adolescent who meets the biochemical criteria for GH deficiency in adulthood, but does not show alterations of metabolism, body structure, or emotional state, should GH treatment be started in adolescence, or only if and when the clinical syndrome becomes apparent? This is a difficult question to which there is not yet any clear answer, and we suggest that there is a need for further studies in this area. Furthermore, it will be necessary to re-evaluate the situation of patients who have completed their growth, and definitive conclusions will require controlled studies.

Role of glucocorticoids in the neuroregulation of growth hormone secretion.

Elevated glucocorticoid (GC) levels produce a marked impairment in somatic growth in both rodents and primates. In addition, GC play an important role in the regulation of growth hormone (GH) synthesis and secretion. Blunted GH response to stimulation tests in conditions of chronic exposure to excessive cortisol secretion or administration are well documented. In contrast, acute administration of GC to normal human subjects induces a transient increase in plasma GH levels. This dual action of GC on GH secretion is probably due to the fact that they act at different loci; i.e. in the regulation of GH transcription and GHRH and somatostatin receptors at the pituitary level as well as GHRH, somatostatin and GH receptor gene expression at the hypothalamic level.

Growth hormone releasing hexapeptide-6 (GHRP-6) test in the diagnosis of GH-deficiency.

Pituitary GH reserve can be assessed by substances that act directly at the somatotroph, such as GHRH, or by a variety of metabolic and neuropharmacological tests acting at the hypothalamic level, such as hypoglycemia, clonidine or L-Dopa. In order to evaluate GHRP-6 as a test of pituitary GH reserve, we studied GH responses of i.v. administered GHRP-6 in a group of short-statured children, as well as in a group of adults diagnosed with growth hormone deficiency (GHD) by conventional GH testing. Although we found that the GH response to GHRP-6 was lower in patients with GHD than in normal children, on an individual basis a considerable degree of overlap was observed between the two groups. In contrast, we found an almost complete blockade of GH response to either GHRP-6 or GHRH plus GHRP-6 in patients with pituitary stalk transection, suggesting that this could be a cost-effective test for the diagnosis of this condition. A similar finding was also obtained in GH response to the combined administration of GHRH plus GHRP-6 in patients with GHD of adult onset; this test may well prove valuable in the diagnosis of this clinical entity.

[Urinary tract infection at the emergency service of a third level hospital]. / Infección urinaria en la urgencia hospitalaria de tercer nivel.

104 patients with (UI) non-complicated urinary infection, diagnosed at the emergency department of a third level hospital, are presented. The median age (x +/- DE) was of 58.12 +/- 20, 48 years; 78 were female (73%) and 22 male. 81 had fever and/or micturitional syndrome, the rest of the patients were without symptoms. The most frequent germ was escherichia coli, which was isolated in 80 patients (84.6%) followed by proteus mirabilis in 9 patients (8.6%) and enterococo in 2 patients (1.9%), other differing germs were also isolated, one for each remaining case. The only active antibiotic "in vitro" for all the germs isolated was gentamicin; other showed varying resistance. The best effectivity "in vivo" was also obtained with gentamicin followed by cotrimoxazole, despite the resistance which was superior to cefalexin. There were no deaths reported during the ambulatory treatment. We concluded that non-complicated UI can be treated in an ambulatory regimen. The most effective antibiotic is gentamicin, cotrimoxazole being a valid alternative.

[Tracheal rupture during a transhiatal esophagectomy without thoracotomy. Intra- and postoperative treatment]. / Rotura traqueal en el curso de una esofagectomía transhiatal sin toracotomía. Tratamiento intra y postoperatorio.

We report the case of a male patient with a carcinoma of the upper third of the esophagus who presented a tracheal rupture during a transhiatal esophagectomy. The clinical picture was characterized by a severe alteration of the ventilatory function that required selective intubation and, later on, a right thoracotomy for repairing the tracheal lesion. After surgery the patient was treated at the Recovery Unit. He received high-frequency mechanic ventilation (jet ventilation type) during nine days in a attempt to decrease the risk for dehiscence of the tracheal suture and to ensure an adequate oxygenation and hemodynamic control. The clinical course was favourable.