Consensus of the Spanish society of laboratory medicine and the Spanish society of medical oncology on the methodology and criteria for evaluation of circulating tumour markers in breast cancer.

The measurement of circulating tumour markers (TMs) for the diagnosis or monitoring of breast cancer has sometimes been considered of limited utility. In addition to the overinterpretation of irrelevant changes in marker levels, the characteristics of the patient, the disease or other pathologies that can modify them are often not considered in their evaluation. On the other hand, there are recent data on the relationship of TMs with molecular subtypes and on their prognostic value, the knowledge of which may improve their clinical utility. This consensus article arises from a collaboration between the Spanish Society of Laboratory Medicine (SEQCML) and the Spanish Society of Medical Oncology (SEOM). It aims to improve the use and interpretation of circulating TMs in breast cancer. The text summarizes the current knowledge and available evidence on the subject and proposes a series of recommendations mainly focussed on the indication, the frequency of testing and the factors that should be considered for correctly interpreting changes in the levels of TMs.

Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05) by 10-5 M L-NAME (a direct inhibitor of nitric oxide synthase), 10-7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase), 10-6 M KT 5823 (an inhibitor of protein kinase G), 10-2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker) and 10-7 M apamin plus 10-7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively), and was blocked by 8×10-2 M potassium (a high concentration) and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.

Benign episodic mydriasis. Experience in a specialist neuro-ophthalmology clinic of a tertiary hospital.

INTRODUCTION: Anisocorias are a relatively frequent reason for consultation in neuro-ophthalmology units. They remain a diagnostic challenge for specialists as they may be due to several etiological factors. In the absence of other accompanying symptoms, anisocorias are usually due to benign processes. Benign episodic mydriasis (BEM) is an isolated cause of intermittent pupil asymmetry, in which the pathophysiology is still not fully understood, and is predominant in young women with migraine. SUBJECTS, MATERIAL AND METHODS: We describe the epidemiological and clinical characteristics of patients with BEM, assessed in a neuro-ophthalmology unit in a tertiary hospital. RESULTS: A total of 7 patients were diagnosed with BEM, all of them females, with a mean age of 33 ± 10 yrs. The patients presented with pupil asymmetry (n = 5) and blurred vision (n = 2), and 6 of the 7 patients had unilateral involvement. The duration of impairment varied from a few minutes to 48 hrs. Four patients (57%) had a clinical history of migraine without aura. The episodes in these 4 patients were recurrent (75%), often lasted for a few minutes (75%), and had associated blurred vision (50%). The neuroimaging studies were normal. DISCUSSION: BEM appears predominantly in young women. It is frequently related to a previous history of migraine, and the specialist must consider if it is a concomitant symptom of common migraine, migraine with aura, or ophthalmoplegic migraine. Although BEM has unilateral predominance, there may be alternation of the affected eye or even bilateral impairment during the same episode, which makes us question the adequacy of the term to describe the process. Imaging tests are not recommended in the absence of other accompanying symptoms, or in short-term episodes.

Prolactin fractions from lactating rats elicit effects upon sensory spinal cord cells of male rats.

Recently it has been suggested that the neurohormone prolactin (PRL) could act on the afferent nociceptive neurons. Indeed, PRL sensitizes transient receptor potential vanilloid 1 (TRPV1) channels present in nociceptive C-fibers and consequently reduces the pain threshold in a model of inflammatory pain. Accordingly, high plasma PRL levels in non-lactating females have been associated with several painful conditions (e.g. migraine). Paradoxically, an increase of PRL secretion during lactation induced a reduction in pain sensitivity. This difference could be attributed to the fact that PRL secreted from the adenopituitary (AP) is transformed into several molecular variants by the suckling stimulation. In order to test this hypothesis, the present study set out to investigate whether PRL from AP of suckled (S) or non-suckled (NS) lactating rats affects the activity of the male Wistar wide dynamic range (WDR) neurons. The WDR neurons are located in the dorsal horn of the spinal cord and receive input from the first-order neurons (Ab-, Ad- and C-fibers). Spinal administration of prolactin variant from NS rats (NS-PRL) or prolactin variant from S rats (S-PRL) had no effect on the neuronal activity of non-nociceptive Ab-fibers. However, the activities of nociceptive Ad-fibers and C-fibers were: (i) increased by NS-PRL and (ii) diminished by S-PRL. Either NS-PRL or S-PRL enhanced the post-discharge activity. Taken together, these results suggest that PRL from S or NS lactating rats could either facilitate or depress the nociceptive responses of spinal dorsal horn cells, depending on the physiological state of the rats.

[Usefulness of electroencephalograms in evaluating transient global amnesia]. / Utilidad de la electroencefalografia en la valoracion de la amnesia global transitoria.

INTRODUCTION: Transient global amnesia (TGA) is a perfectly well defined clinical picture, but nevertheless even today its aetiology remains unknown. The three most widely accepted theories suggest it has a vascular origin, it is related with the pathophysiology of migraine or it is of an epileptiform nature. AIM: To analyse whether there is an electroencephalographic pattern that is consistently repeated in a series of electro-encephalograms (EEG) carried out on patients with TGA. PATIENTS AND METHODS: The study consists in a retrospective analysis of a sample of 345 patients referred to have an EEG after an episode of TGA. RESULTS: In almost 20% of the EEGs something that could be considered abnormal was found, although most of these findings (64%) were of little pathological significance. Of the remaining 26%, attention should be drawn to the cases of two patients with subclinical rhythmic electroencephalogram discharges of adults (a pattern with a meaning that is not altogether clear and which has previously been associated with TGA). CONCLUSIONS: A considerable percentage of patients have TGA and EEG alterations, although most of them are of scarce pathological significance or can be attributed to some other underlying condition. We have not succeeded in identifying any pattern that is consistently repeated. Our results suggest that the EEG is a test with low diagnostic effectiveness in this pathology and it is necessary to reconsider the need to systematically perform such tests in suspected cases of TGA.

Neoplastic meningitis.Review of a clinical series.

INTRODUCTION: The increase in the ageing population in the last decades has led to an increased frequency of cancer-associated complications. Among these, neurological disorders stand out, as they appear in 10-30% of patients with systemic neoplasia. Neoplastic meningitis accounts for 4-15% of patients with solid tumours and it has a poor prognosis. The objective of this paper is to describe the clinical, imaging and prognostic characteristics as well as cerebrospinal fluid findings in a series of neoplastic meningitis. BACKGROUND AND DEVELOPMENT: We performed a retrospective review of all patients admitted to the Hospital Universitario of Gran Canaria Dr. Negrín with clinical suspicion of neoplastic meningitis between 1990 and 2008. We selected 37 patients with an average age ranging from 15 to 75 years old. A total of 81.8% of the cases in which a primary tumour was found were associated with solid tumours (24.2% were located in the breast, and 24.2% in the lung). The most frequent sign of cranial nerve dysfunction was dyplopia, which was observed in 32.4% of the cases. The average survival rate after diagnosis was 87.9 days (12.6 weeks). The cerebrospinal fluid cytology was positive in 46.4% of the cases. CONCLUSION: Neoplastic meningitis is a severe complication of both solid and haematological tumours. We stress the importance of maintaining a high level of suspicion to achieve early diagnosis, since the average survival probability for neoplastic meningitis patients is low.

[Headache in idiopathic intracranial hypertension]. / Cefalea en la hipertensión intracraneal idiopática.

INTRODUCTION: Idiopathic intracranial hypertension (IICH) is characterized by a rising in intracranial hypertension without evidence of intracranial expansive disease. Diagnostic criteria of headache related to IICH are described in the International Classification of Headache Disorders. In clinical practice, however, headache related to IICH may be heterogeneous. PATIENTS AND METHODS: Clinical charts of patients with IICH admitted to the Hospital Universitario de Gran Canaria Dr. Negrin between 1990 and 2007 were retrospectively reviewed. RESULTS: Fifty-five patients were included, with a ratio female/male of 8.1:1. Headache was present in 85.4%. The headache was continuous in 63.8% of patients, and diffuse in 51%. CONCLUSION: Headache related to IICH is heterogeneous, and may mimic primary headache, so a high level of suspicion is needed to avoid diagnostic delay.

Inverse association between serum resistin and insulin resistance in humans.

AIM: To determine how serum concentrations of resistin are distributed in humans in relation to insulin resistance, type 2 diabetes, and obesity. METHODS: Cross-sectional, descriptive study carried out in a random sample (n=713, 43% men, 18-75 years) of general population of inhabitants of the Canary Islands (Spain). Serum resistin concentration, HOMA2-IR, anthropometric parameters, drug consumption and physical activity were recorded. RESULTS: There were no differences in resistin concentration between participants with and without diabetes (3.1+/-0.2 vs. 3.2+/-0.1ng/mL; p=0.566), or between obese and non-obese participants (3.1+/-0.1 vs. 3.2+/-0.1ng/mL; p=0.803). Individuals with abdominal obesity (waist-hip ratio [WHR] >or=1 in men or >or=0.9 in women) had lower concentrations of resistin (3.0+/-0.13 vs. 3.4+/-0.1ng/mL; p<0.001). The correlations between resistin and HOMA2-IR (r=-0.231; p<0.001) and between resistin and WHR (r=-0.202; p<0.001) were inverse. Multivariate analysis corroborated the inverse association of this cytokine with HOMA2-IR, WHR and, in women, also retained in the model the direct association between resistin and physical activity and the inverse association between resistin and antihypertensive agents. CONCLUSIONS: In this population resistin is inversely associated with insulin resistance and abdominal obesity.

Serum resistin and polymorphisms of androgen receptor GAGn and GGNn and aromatase TTTAn.

There is evidence that androgens are regulators of insulin resistance (IR), and may be involved in the regulation of resistin, a cytokine that has been related with IR. Earlier studies found that androgen receptor length polymorphisms CAGn and GGNn and the aromatase polymorphism TTTAn may influence receptor or enzyme activity and serum concentrations of androgens. This study was designed to determine whether polymorphism length was related to serum resistin concentration and to other variables related with IR. In 1,580 persons chosen randomly from the general population of the Canary Islands (Spain), we measured polymorphism length, waist circumference, waist/hip ratio, BMI, and serum glucose concentration. In smaller subgroups, we also measured C-peptide (n = 677), resistin (n = 583), and leptin concentration (n = 754) and estimated IR (homeostasis model assessment-IR (HOMA2-IR)). In men, polymorphism length correlated with resistin concentration (CAGn, r = 0.13, P = 0.031; TTTAn, r = 0.15, P = 0.005; GGNn, r = -0.15, P = 0.026), and the correlations were confirmed in multivariate regression models. The length of CAGn and TTTAn correlated inversely with C-peptide (r = -0.13, P = 0.016 and r = -0.21, P < 0.001, respectively) and with estimated IR (r = -0.12, P = 0.032 and r = -0.19, P = 0.001, respectively). In men, length of the CAGn, GGNn, and TTTAn was associated with serum resistin concentration. These results support the hypothesis that androgens may be involved in the regulation of resistin. Resistin may be a link between IR and androgens.

The GTP-binding protein G alpha s is present in dormant spores and expressed differentially during spore germination of the fungus Phycomyces blakesleeanus.

A DNA sequence homologous to a G alpha s DNA probe, and the corresponding G alpha s protein (stimulatory alpha-subunit of GTP-binding protein) were detected in Phycomyces blakesleeanus. The protein was demonstrated in membrane fractions of dormant spores of this fungus using three different experimental approaches. Photoaffinity-labelling experiments with [alpha-32P]GTP of the membrane fraction revealed two bands, of 56 and 32 kDa. The 56 kDa GTP-binding protein was detected by this method in all the stages of early development and growth investigated. Also, a spore protein of 56 kDa was ADP-ribosylated by cholera toxin, and a 56 kDa protein was detected by Western blotting with a specific antibody against mammalian G alpha s. These results indicate that G alpha s (56 kDa) is present in dormant spores of P. blakesleeanus. Using the ADP-ribosylation and Western blotting assays, G alpha s was detected during all stages of spore germination before the hyphae became highly branched, but it was not detected in the branched hyphae that formed 18 h after the initiation of spore germination. Therefore, G alpha s is expressed differentially during Phycomyces development.

[Cases of hydatidiform mole at the Nuevo Hospital Civil in Guadalajara]. / Mola hidatidiforme en el Nuevo Hospital Civil de Guadalajara.

Thirty nine patients with hydatiform mole with clinical, echosonographic and hormonal diagnosis, were analyzed, from March, 1991 to February 1993 at the Nuevo Hospital Civil de Guadalajara. Incidence was I out of 301 pregnancies; average age, 24.6 years; 35.8% were primigravidae; average amenorreha was 15.6 weeks and there were not complications in 84.6%. The most frequent symptoms were transvaginal bleeding, 92.3%; mole rests expulsion, 25.6% and hyperemesis, 23%. The uterine fundus was larger in 17 patients; smaller in 13; the same in 5 and there were no data for four cases. An uterine curettage was performed in 38 patients; there was hysterotomy performed also for important bleeding; and there were 11 patients transfused. The histopathologic results of hydatidiform mole were confirmed in 84.6%. Only 20% of the patients came back for a post-evacuation control treatment. These results suggest that the characteristics of mola pregnancy at the Nuevo Hospital Civil de Guadalajara are similar to what has been reported in the literature; with a delayed diagnosis and a poor follow up of cases.

Mitogenic action of TGF-beta and insulin in L-929 cell line in serum-free medium.

In serum-free medium, TGF-beta, in a wide range of concentrations, stimulated DNA synthesis. A similar effect was achieved with insulin even after relatively short times. When TGF-beta and insulin were present simultaneously, the mitogenic effect was stronger than the effect achieved by either one separately, but without synergism. The PDGF, which is not mitogenic by itself in this cell line, did not increase the response to TGF-beta. In the presence of fetal bovine serum TGF-beta and insulin DNA synthesis was not stimulated. Two of the most important mitogenic growth factors for L-cells present in serum could be insulin and TGF-beta. Adenosine did not modify the mitogenic response to TGF-beta and insulin. However, in the presence of adenosine PDGF stimulated the growth of L-929. The results suggest that TGF-beta does not stimulate the growth of L-929 via an autocrine production of PDGF-related peptides in a serum-free model. TGF-beta blocked the inhibitory response to estradiol at high concentrations, but it did not affect the inhibitory response due to glucocorticoids. Insulin and TGF-beta caused an enhancement of beta-NGF and c-myc RNA expression. This effect appears much earlier with insulin. This difference suggests that mRNA accumulation provoked by TGF-beta is mediated by other factors. Fetal bovine serum had little effect on the expression of those two mRNAs.