A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study.

BACKGROUND: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting. MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours. RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor. CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.

Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort.

BACKGROUND: Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics. METHODS: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n=565 cases). Multivariable conditional logistic regression models were used to estimate associations. RESULTS: We observed no association between IGF-I and EOC overall or by tumour characteristics. CONCLUSIONS: In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk.

Bortezomib-induced peripheral neurotoxicity in human multiple myeloma-bearing mice.

The proteasome inhibitor bortezomib is an antineoplastic drug mainly used for the treatment of multiple myeloma (MM). Despite its effectiveness, bortezomib clinical use is often limited by the onset of peripheral neuropathy (BiPN). To better understand the mechanisms of BiPN several rat and mice models have been proposed, but no studies in MM-bearing animals allowing to test the antitumor activity of the selected schedules and the role of MM by itself in peripheral nervous system damage have been reported to date. Here, we carried out a study using immunodeficient C.B-17/Prkdcscid (SCID) mice injected with RPMI8266 human MM cells and treated with bortezomib 1 mg/kg once a week for five weeks. Animals were assessed with neurophysiological, behavioral and pathological methods and tumor volume measurement was performed along the study. At the end of the study BiPN was evident in bortezomib-treated animals, and this neurotoxic effect was evident using a schedule able to effectively prevent tumor growth. However, neurophysiological and pathological evidence of MM induced peripheral nervous system damage was also reported. This model based on MM-bearing animals is more reliable in the reproduction of the clinical setting and it is, therefore, more suitable than the previously reported models of BiPN to study its pathogenesis. Moreover, it represents an optimal model to test the efficacy of neuroprotective agents and at the same time their non-interference with bortezomib antineoplastic activity.

Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk. METHODS: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method. RESULTS: No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood ratio test (LRT) P-value: 0.01, n=203). CONCLUSIONS: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.

Circulating prolactin and breast cancer risk among pre- and postmenopausal women in the EPIC cohort.

BACKGROUND: Experimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of prediagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor status of the breast tumors. PATIENTS AND METHODS: Conditional logistic regression was used to analyze the data from a case-control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects. RESULTS: Statistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (Phet = 0.04). Higher serum levels of prolactin were associated with significant increase in the risk of breast cancer among postmenopausal women [odds ratio (OR)Q4-Q1 = 1.29 (95% confidence interval, CI, 1.05-1.58), Ptrend = 0.09]; however, this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation [ORQ4-Q1 = 1.45 (95% CI 1.08-1.95), Ptrend = 0.01], whereas no statistically significant association was found for the non-users of HRT [ORQ4-Q1 = 1.11 (95%CI 0.83-1.49), Ptrend = 0.80] (Phet = 0.08). Among premenopausal women, a statistically non-significant inverse association was observed [ORQ4-Q1 = 0.70 (95% CI 0.48-1.03), Ptrend = 0.16]. There was no heterogeneity in the prolactin-breast cancer association by hormone receptor status of the tumor. CONCLUSION: Our study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.

Neuroanatomy of financial decisions.

INTRODUCTION: Neuroeconomics is a new science that studies the brain processes involved in taking decisions, particularly related to economy and it has experienced an important advance in the recent years due to the development of the new neuroimaging techniques, basically functional magnetic resonance imaging. The aim of this paper it to carry out a review of the literature on the different neurological mechanisms involved in taking financial decisions, the concerned brain structures and the diseases that can affect them. SOURCES: We made a non systematic review of the literature in primary (PubMed) and secondary (Tripdatabase and Cochrane Library) bibliographic databases. We also used bibliography given by the Asociación Española de Neuroeconomía. DEVELOPMENT: Brain reward and loss aversion systems suppose a balance that makes us take one or another decision. Dopamine plays an important role on it and several brain structures have been involved in this balance such as the amygdale, the insula, the medial prefrontal cortex, the anterior and posterior cingulated cortex, the accumbens nucleus and the ventral tegmental area. The alteration of this balance may produce inappropriate financial behaviors what may occur in common diseases including depression, mania, alcoholism, gambling and several impulse control disorders. CONCLUSIONS: Neurologists should define our role in this interdisciplinary field due to the privileged position of our specialty to study how the brain works and due to the potential growing of this science in the near future.

Neuropathological changes in the peripheral nervous system and spinal cord in a transgenic mouse model of Niemann-Pick disease type A.

OBJECTIVE: Type A Niemann-Pick is a severe neurological disease, caused by a mutation of the gene of acid sphingomyelinase (ASM) and reduced enzyme activity. Some studies reported neuropathological changes occurring in the central nervous system of ASM deficient transgenic (ASMKO) mice, while a detailed study on the peripheral nervous system (PNS) at different ages is currently lacking. The aim of our study was to examine the pathological changes occurring in the PNS and in the spinal cord in an AMSKO model of Niemann-Pick disease (NPD) Type A. MATERIAL AND METHOD: Dorsal root ganglia (DRG), peripheral nerves and spinal cord specimens were obtained from ASMKO mice and age-matched wild type animals (age range = 1-7 months). They were observed at the light and electron microscope. Behavioral testing was performed to assess motor coordination and reactivity. Fluoro-Jade B was used as a high affinity fluorescent marker for degenerating neurons. RESULTS: Typical NPD cytoplasmic inclusions were observed in DRG neurons and satellite cells, in peripheral nerve Schwann cells, in spinal cord neurons and in endothelial cells. All these inclusions were present from the age of 1 month and increased with aging. By Fluoro-Jade B staining we demonstrated the occurrence of neuronal degeneration starting from 5 months of age. CONCLUSION: Despite the fact that a definite diagnosis of NPD Type A depends on enzymatic assays and/or molecular analysis, morphological investigation remains an important diagnostic procedure. Well-defined and complete neuropathological information about the ASMKO mouse model, inclusive of PNS examination, may be crucial in the pre-clinical evaluation of new therapies.

Human platelets express the synaptic markers VGLUT1 and 2 and release glutamate following aggregation.

Vesicular glutamate transporters (VGLUTs) are involved in storing glutamate for secretion at the level of glutamatergic axon terminals, and for this reason they have been extensively used as markers to identify glutamate-releasing cells. Platelets have been considered as a suitable model for studying glutamatergic dysfunction because they perform glutamate uptake and express both external transporters, and NMDA-like receptors. Here, we show that platelets express the pre-synaptic markers VGLUT1 and VGLUT2 and release glutamate following aggregation, implying a possible contributory role in the pathophysiology of stroke, migraine, and other excitotoxic disorders.

Cystic pyeloureteritis: review of 34 cases. Radiologic aspects and differential diagnosis.

OBJECTIVES: To refine the clinical and radiologic description of an unusual benign disease, cystic pyeloureteritis (CPU), consisting of the appearance of suburothelial cysts that raise the mucosa layer of the urothelium. We also studied its relationship with various types of inflammation, including chronic infection, that may be the stimulus for the appearance of CPU. METHODS: We compiled 34 cases of CPU covering the period 1976 to 1994, analyzing the clinical manifestations, diagnostic procedures, differential diagnosis, and evolution. RESULTS: There are no specific symptoms associated with the presence of cysts. The average age of the patients was 59 years (range 30 to 77). Urinary tract infection was detected in 18 (53%). The pyeloureteritis was unilateral in 27 (79%) and bilateral in 7 (21%) of the patients. The location of the cysts was as follows: 1 pyelic (3%); 6 pyeloureteral (18%); and 27 (79%) ureteral. Resolution of the radiologic alterations depends on the resolution of the associated pathology: infections, lithiasis, and obstruction. CONCLUSIONS: We conclude that CPU is a benign pathology with indolent evolution and variable duration; it is not associated with sequelae. Diagnosis is made on the basis of radiologic findings, mainly intravenous urography; in view of the minor entity of the pathology, biopsy is not advisable if the radiologic findings are conclusive.

TPA prognostic value in superficial bladder cancer.

We determined the levels of TPA in 133 patients with superficial bladder cancer. 79 cases were Ta stages, and 54 cases T1 stages. 53 of the tumors were well differentiated (I), 65 moderately differentiated (II) and 15 undifferentiated (III). The average follow-up time of these patients was 8.3 months; the standard deviation being 5.2 months (median value 7 months). In 43 cases a relapse of the tumor was observed. We detected high TPA levels in 25% of the patients, without observing meaningful differences in tumor invasion or in its differentiation degree. The usefulness of the TPA, the degree of tumor invasion, and the degree of cell differentiation were evaluated by means of single-variate and multivariate analysis in order to forecast tumor relapse. Only the TPA had a prognostic value, the relative risk of developing relapse being 2.03 times higher in patients with high TPA than patients with normal TPA.

Usefulness of urinary nuclear matrix protein 22 (NMP22) as a marker for transitional cell carcinoma of the bladder.

OBJECTIVES: The purpose of this study was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22, as a novel marker for urothelial cancer. PATIENTS AND METHODS: NMP22 values were determined for 71 patients and 21 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of entry into the study. Each sample was assayed for levels of NMP22. RESULTS: When the cut-off value was set at 10 U/ml, the positive rate for urinary NMP22 in bladder cancer was 37.8% (17 out of 45), whereas that in post-treatment cases and benign diseases was 30.8% (8 out of 26) compared to 14.3% (3 out of 21) for healthy volunteers. This cut-off value provided a sensitivity of 37.8% and a specificity of 80.9%. In the bladder cancer group, NMP22 levels were related to tumor size, shape, grade and stage. CONCLUSIONS: Despite the many reports that suggest NMP22 as a promising urinary marker for monitoring transitional cell carcinoma, this study does not support its usefulness as a substitute tool for urinary cytology in the control of bladder tumors.

[Vasectomy and arteriosclerosis: are they related?]. / Vasectomía y arteriosclerosis: están relacionadas?

There has been a remarkable increase in recent years in the demand by the male population of vasectomy procedures as a sterilization technique. Several recent studies have questioned its safety. We have evaluated in 103 healthy males the effect of vasectomy on plasma lipoprotein concentration, blood pressure and body mass index, all acknowledged risk factors for arteriosclerosis. No statistically significant change was found either in plasma lipoprotein concentration or blood pressure. The only statistically significant (p < 0.05) change was in terms of body mass index, which experiences a mean increase of 1.22%. Our results cannot confirm that vasectomy plays a role as risk factor for arteriosclerosis.

PIP: 103 men who underwent elective vasectomy between October 1991 and October 1992 at the Sant Joan de Deu Hospital in Barcelona participated in a study to determine whether plasma lipoprotein concentrations, blood pressure, and body mass index showed alterations from the prevasectomy state 3 months after the procedure. The preoperative physical examination included questions about risk factors for arteriosclerosis, smoking, alcohol consumption, diet, and exercise. The average age of the men was 38 years. The only study variable showing significant alteration after 3 months was the body mass index, which increased by 1.2%. Total cholesterol declined by 2.1%, triglycerides by 22.1%, and HDL cholesterol by 3.2%, while LDL cholesterol increased by 0.5%; the changes were not significant. The study results do not support the theory that vasectomy constitutes a risk factor for arteriosclerosis, at least in the short run.

[Congenital urethral diverticulum]. / Divertículo uretral congénito.

Presentation of two cases of congenital diverticula of the bulbar urethra. The objective of this paper is to discuss the etiopathogenic theories, sings and symptoms, current diagnostic methods and therapeutic indications, and to conclude that this type of diverticula do not present a florid symptomatology, endoscopy being the best diagnostic and therapeutic method. Finally, a review of the literature is made based on two clinical cases.

[Prostatic adenocarcinoma presenting as retrovesical cystic formation. Report of a case]. / Presentación de un adenocarcinoma prostático como formación quística retrovesical. A propósito de un caso.

Presentation of one case of prostate adenocarcinoma with a peculiar evolution towards a large cystic formation at the expense of the left prostate lobe, clinically revealed as a picture of poor performance status and impaired consciousness secondary to obstructive renal failure. The benign evolution of the case, even though the patient received no specific therapy, is emphasized.

[Role of tissue polypeptide antigen as a marker in bladder cancer]. / Papel del TPA como marcador tumoral en el cáncer de vejiga.

Presentation of a review of TPA serum levels in 207 patients, 160 of which had vesical carcinoma. This population comprises 37 patients who had suffered vesical carcinoma but whom, at entry in the study, did not display clinic evidence of that: 11 patients with benign vesical pathology; 84 patients with primary vesical tumour, and 76 patients with relapsing vesical tumour. Tumoral staging resulted in 72 Ta, 49 T1, 10 T2, 14 T3, and 15 Ta. Distribution with regard to degree of differentiation was as follows: 52 GI, 61 GII and 40 GIII. Sensitivity of serum TPA in our series was 39% and specificity 94%. When tumours were subdivided into surface and infiltrant tumours, sensitivity was 28% and 72% respectively (p < 0.01). Patients presenting normal levels of serum TPA took longer to relapse than those who had high levels. Mean time to relapse was 17 months for the first group, and 12 months for the second group. Serum TPA increased its performance with carcinomas of higher grade and stage, but it does not have enough sensitivity to be considered a useful marker in low stages. However, serum TPA relationship to the tumour's invasive degree and the disease-free interval are an indication for their likely use as a prognostic factor to delimit the groups with higher risk of relapse.

[Prostatic abscess: diagnosis and treatment]. / Abscesos prostáticos: diagnóstico y tratamiento.

Prostatic abscesses are an infrequent pathology, probably due to a better and early management of prostatic infections. Predisposing factors in this pathology are diabetes mellitus, urethral catheterism or manipulation, and immunodepressed states like AIDS. Nowadays, ultrasonography is an excellent diagnostic method of this pathology, and serves as a guidance of directed drainage. We present five cases in which the size of the abscess was determining in relation to the therapeutic attitude. Abscesses of less than 2 cm, measured by transrectal ultrasonography, can be evacuated by directed puncture, followed by antibiotic treatment. When the diameter of the abscess is greater than 2 cm, we realize a perineal drainage with a catheter placed with transrectal ultrasonography. Currently, TUR and other methods seems to be overcome.

[Leydig cell tumor, gynecomastia, and inferior vena cava thrombosis]. / Tumor de células de Leydig, ginecomastia y trombosis de vena cava inferior.

Leydig cell tumor is a testicular tumor with a low incidence characterized by a high estrogens secretion from the tumoral cells. Its more frequent clinical presentation is a testicular nodule with or without other endocrine manifestations due to estrogenic hypersecretion. We're reporting a case of a Leydig cell tumor with high plasmatic levels of estradiol, gynecomastia and inferior cava vein thrombosis, which hasn't been described among its clinical features up to now. Vascular thrombotic phenomenons have already been reported in other clinical situations with hiperestrogesism and they could also be associated with these tumors. Patients with Leydig cell tumors could be at a higher risk of developing thromboembolic phenomenons because of tumoral hyperestrogenism and could present thrombotic complications among the clinical findings.

[Congenital preauricular sinuses]. / Las fístulas congénitas preauriculares.

The following presentation of 2 cases give us the chance of making a review of the current situation and the correct handling of the congenital preauricular sinuses. Although some authors consider this pathology within the group of latero-cervical fistulae, we think that they should be individualized. The most frequent sitting is before the helix. They are generally asymptomatic, and it is not strange that the motive of consultation are recurrent infections or following surgery. The treatment consists in complete operative resection.

[Infective stomatitis of the palate]. / Localización palatina de las estomatitis infecciosas.

Having on base a wide and selective review of the literature, it has seemed to us interesting to detail the infective pathology on this location or sometimes occurring. This region is, as well will see, the seat of a rich pathology. We pretend on the other hand to reassess the importance of the meticulous examination of the oral cavity in "systemic problems". We describe the palatal infections divided in four groups: bacterial, viral, fungal and parasitory, according to the causal agent. We review the palatine manifestations of other fewer current syndromes as well.

Short-term dynamics of culturable bacteria in a soil amended with biotransformed dry olive residue.

Dry olive residue (DOR) transformation by wood decomposing basidiomycetes (e.g. Coriolopsis floccosa) is a possible strategy for eliminating the liabilities related to the use of olive oil industry waste as an organic soil amendment. The effects of organic fertilization with DOR on the culturable soil microbiota are largely unknown. Therefore, the objectives of this study were to measure the short-term effects of DOR and C. floccosa-transformed DOR on the culturable bacterial soil community, while at the same time documenting the bacterial diversity of an agronomic soil in the southeastern Iberian Peninsula. The control soil was compared with the same soil treated with DOR and with C. floccosa-transformed DOR for 0, 30 and 60 days. Impact was measured from total viable cells and CFU counts, as well as the isolation and characterization of 900 strains by fatty acid methyl ester profiles and 16S rRNA partial sequencing. The bacterial diversity was distributed between Actinobacteria, Alphaproteobacteria, Gammaproteobacteria, Betaproteobacteria, Bacilli, Sphingobacteria and Cytophagia. Analysis of the treatments and controls demonstrated that soil amendment with untransformed DOR produced important changes in bacterial density and diversity. However, when C. floccosa-transformed DOR was applied, bacterial proliferation was observed but bacterial diversity was less affected, and the distribution of microorganisms was more similar to the unamended soil.