Insuficiencia ovárica prematura / Premature ovarian insufficiency

RESUMEN La insuficiencia ovárica prematura es la pérdida de la función ovárica antes de los 40 años de edad. Se caracteriza por hipogonadismo hipergonadotrófico y amenorrea u oligomenorrea. Su etiología es multifactorial, pudiendo deberse a causas iatrogénicas, genéticas, metabólicas, autoinmunes y ambientales; siendo de origen idiopático en el 90 % de los casos. Su incidencia es de 1 cada 100 mujeres menores de 40 años y 1 cada 1000 mujeres menores de 30 años. En la actualidad no existe un único marcador que se pueda utilizar para calcular la reserva ovárica; sin embargo, en los últimos años la hormona antimülleriana ha demostrado presentar algunas ventajas respecto a los biomarcadores clásicamente utilizados. Además, diversos estudios indican que existe una correlación positiva entre los niveles de esta hormona y el recuento de folículos antrales, que es, por el momento, el método más confiable para evaluar reserva ovárica debido a las actuales dificultades técnicas para la determinación de hormona antimülleriana.

ABSTRACT Premature ovarian insufficiency, the loss of ovarian function before the age of 40 years, is characterized by hipergonadotrofic hipogonadism and amenorrhea or oligomenorrhea. The etiology is multifactorial, and can be due to genetic, metabolic, autoimmune, environmental or iatrogenic causes, being idiopathic 90% of cases. Currently there is not a single marker that can be used for estimate ovarian reserve in this patients; however, in recent years antimüllerian hormone has proved to have some advantages over other classical biomarkers. Moreover, several studies indicate a positive correlation between antimüllerian hormone concentration and antral follicle count, considered nowadays the most reliable method for ovarian reserve estimation.

Environmental factors driving the occurrence of the invasive cyanobacterium Sphaerospermopsis aphanizomenoides (Nostocales) in temperate lakes.

Cyanobacterial blooms are an increasing threat worldwide. Invasions of certain cyanobacterial species, mainly towards higher latitudes, add to this concern as they enrich the pool of potential bloom-formers in the invaded region. Among the numerous causes of this escalating process, climate warming is commonly considered the most crucial factor, but empirical studies of this issue are lacking. The aim of our study was to identify physical, chemical and biological factors related to the occurrence of an invasive cyanobacterium at the northern border of its putative current range, and thus enabling its expansion. This study focuses on the relatively little studied species Sphaerospermopsis aphanizomenoides (Nostocales, Cyanobacteria; synonyms: Aphanizomenon aphanizomenoides, Anabaena aphanizomenoides), which is predicted to become one of the main nuisance species of the future. Forty-nine freshwater lakes located between latitudes 51° and 55°N were examined for the presence of S. aphanizomenoides, and environmental factors that could drive its occurrence were studied simultaneously. To identify factors correlated with the presence of the species, principal component analysis (PCA) and Mann-Whitney U test were performed. Water temperature did not differentiate lakes with or without S. aphanizomenoides, however the study was conducted in a particularly hot summer. Total phosphorus concentration was identified as the primary driving factor of the occurrence of S. aphanizomenoides. The species grew in poor light conditions and high phytoplankton biomass, mainly in shallow lakes. As shown by detrended correspondence analysis (DCA), the species accompanied shade tolerant, eutrophic species of native and invasive cyanobacteria as well as eukaryotic algae. Our results indicate that eutrophication may be the primary factor enabling the increasing occurrence of S. aphanizomenoides in temperate environments, and suggest that this process may stimulate expansion of cyanobacterial species towards high latitudes.

Catecolaminas vs. metanefrinas en el diagnóstico bioquímico de feocromocitoma y paraganglioma / Catecholamines vs. metanephrines in the biochemical diagnosis of pheochromocytoma and paraganglioma

RESUMEN Los tumores secretores de catecolaminas, feocromocitoma y paraganglioma son entidades poco frecuentes y potencialmente letales si no son diagnosticadas y tratadas a tiempo. El laboratorio cumple un rol fundamental en el diagnóstico y seguimiento de estos tumores a través de la evidencia bioquímica de un exceso de catecolaminas. Sin embargo, muchas veces suele ser dificultoso arribar a un diagnóstico temprano, debido a la baja incidencia de estos tumores y a la dificultad de hallar laboratorios con equipamiento especializado. El marcador bioquímico y las técnicas utilizadas para su medición han ido cambiando con el correr de los años. Tradicionalmente, la medición de catecolaminas en orina era la prueba bioquímica utilizada. Posteriores hallazgos de metabolitos aumentados en la orina de paciente llevaron al uso de ensayos colorimétricos para la detección de ácido vainillin mandélico y metanefrinas como marcadores diagnósticos adicionales de tumor. Las pruebas actuales para el diagnóstico bioquímico muestran una excelente precisión diagnóstica. La medición de metanefrinas libres de plasma utilizando cromatografía líquida de alta resolución con detección electroquímica o de espectrometría de masas en tándem proporciona la máxima precisión para el diagnóstico de estos tumores.

ABSTRACT Catecholamine-secreting neuroendocrine tumors called Pheochromocytoma and Paraganglioma are rare entities, but potentially lethal if diagnosis and treatment are not established early enough. Clinical Laboratory plays an important role in the diagnosis and follow-up of these tumors, through the biochemical evidence of a hyperproduction of catecholamines and its metabolites.

Expression of HLA-DQA1 and HLA-DQB1 genes in B lymphocytes, monocytes and whole blood.

Differential expression of HLA-DQA1 and HLA-DQB1 gene alleles was analysed in three different cell populations isolated from peripheral blood-B lymphocytes, monocytes and whole-blood cells. Interallelic differences in mRNA levels were observed: DQA1*03 alleles were among the most expressed in all cell types, whereas DQA1*05 alleles were least expressed in whole blood and monocytes and among the most expressed in B cells. For DQB1 gene, DQB1*06 group of alleles were the most expressed, and DQB1*02 group the least expressed within all cell populations examined. In comparison with the rest alleles, DQB1*06 and DQB1*05:02 alleles have higher expression in monocytes than in B cells, professional antigen-presenting cells. Cell type-specific regulation of expression was observed as well, with higher and more balanced expression of alleles in B lymphocytes compared to monocytes.

[Comparative analysis of the informative value of 18F-fluorodeoxyglucose and 11C-methionine positron emission tomography in the differential diagnosis of solitary lung masses].

OBJECTIVE: To study the possibilities of enhancing the efficiency of differential diagnosis of solitary lung masses by optimizing the quantitative analysis of positron emission tomography (PET) data when two radiopharmaceuticals (RP) (18F-fluorodeoxyglucose (18F-FDG) and 11C-methionine) are used alone and in combination. MATERIAL AND METHODS: A comprehensive examination involving 18F-FDG and 11C-methionine PET was made in 116 patients with solitary lung masses of various genesis. A final diagnosis in the examinees was established from the results of postoperative material morphological analysis and/or laboratory tests and those of X-ray follow-up. RESULTS: No 18F-FDG and 11C-methionine hyperfixation was found in patients with benign tumors and in the majority of patients with focal pneumofibrosis. At 18F-FDG and 11C-methionine PET, RP accumulation was recorded in all patients with lung cancer (LC) and in patients with inflammatory diseases. Three patients with 18F-FDG PET-negative typical carcinoid tumors were noted to have increased 11C-methionine uptake. At 11C-methionine PET, RP accumulation was recorded in the projection of formation in all the patients with LC and in 38 of the 42 patients with inflammatory diseases. Regardless of the used RP, the Standardized Uptake Value (SUV) was significantly lower in the patients with inflammatory diseases than in those with LC (p ≤ 0.05). CONCLUSIONS: When RP is used alone, the diagnostic efficiency of C-methionine PET in the differential diagnosis of lung tumors and inflammations is higher than that of 18F-FDG PET. At the same time, the highest PET is seen when 18F-FDG and 11C-methionine are used in combination.

The impact of the sequence of pulmonary vessel ligation during anatomic resection for lung cancer on long-term survival--a prospective randomized trial.

PURPOSE: The aim of this prospective randomized trial was to assess the influence of the sequence of pulmonary vessel ligation, during anatomic resection, on long term survival in patients with NSCLC. MATERIAL/METHODS: This prospective randomized study included 385 patients treated surgically with lobectomy or pneumonectomy and standard lymphadenectomy between 1999 and 2003. Patients were randomly assigned to either primary ligation of the pulmonary artery or arteries (group A - 215 patients) or of the pulmonary vein or veins (group V - 170 patients). Patients were excluded if the sequence of vessel ligation was affected by technical difficulties or anatomic limitations. Univariate and multivariate analyses included: the sequence of vessel ligation, age, gender, tumor histology, stage (TNM), and cause of death (cancer related or non-cancer related). RESULTS: Median follow-up was 63 months. The groups were comparable regarding gender, histology, type of resection, and T, N, and overall stage. Overall, 5-year survival reached 50% in group A and 54% in group V (p = 0.82) and did not differ significantly in cancer related and non-cancer related deaths (p = 0.67 and p = 0.26, respectively). Univariate analysis identified higher T and N factors, advanced stage, pneumonectomy, male sex, and older age as negative prognostic factors. Multivariate analysis demonstrated that age, T3-4 disease, and nodal involvement were associated with inferior survival. CONCLUSIONS: The sequence of pulmonary vessel ligation during anatomic resection for non-small cell lung cancer does not significantly affect long-term survival.

Relationship of body mass index in young adulthood and health-related quality of life two decades later: the Coronary Artery Risk Development in Young Adults study.

OBJECTIVE: The expanding overweight and obesity epidemic notwithstanding, little is known about their long-term effect on health-related quality of life (HRQoL). The main objective of this study was to investigate whether overweight (body mass index (BMI) 25 to <30 kg m(-2)) and obese (BMI ≥ 30 kg m(-2)) young adults have poorer HRQoL 20 years later. METHODS: We studied 3014 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a longitudinal, community-dwelling, biracial cohort from four cities. BMI was measured at baseline and 20 years later. HRQoL was assessed by the Physical Component Summary (PCS) and the Mental Component Summary (MCS) scores of the Medical Outcomes Study 12-Item Short-Form Health Survey at year 20. Higher PCS or MCS scores indicate better HRQoL. RESULTS: Mean year 20 PCS score was 52.2 for normal weight participants at baseline, 50.3 for overweight and 46.4 for obese (P-trend <0.001). This relation persisted after adjustment for baseline demographics, general health, and physical and behavioral risk factors and after further adjustment for 20-year changes in risk factors. No association was observed for MCS scores (P-trend 0.43). CONCLUSION: Overweight and obesity in early adulthood are adversely associated with self-reported physical HRQoL, but not mental HRQoL 20 years later.

Mycobacterium avium-intracellulare-associated acute interstitial nephritis: a rare cause of renal allograft dysfunction.

Nontuberculous mycobacterium (NTM) infections are unusual in the renal transplant population. We present a case of disseminated Mycobacterium avium-intracellulare in a renal transplant recipient who was negative for human immunodeficiency virus infection. Our patient developed renal allograft dysfunction in the setting of disseminated disease and reduced immunosuppression. Transplant biopsy showed acute interstitial nephritis with granulomas and acid-fast bacilli. Acute renal failure resolved completely with further reductions in immunosuppression and anti-mycobacterial therapy. Our patient demonstrates the challenges in diagnosis and treatment of this rare infectious complication.

[Special medical strategy in patients with decompensated stenosis of the trachea of malignant genesis].

The article presents a generalized experience with treatment of 49 patients with malignant stenosis of the trachea complicated by respiratory insufficiency. Different methods of endoscopic recanalization of the stenosed portion of the trachea are analyzed. Factors are shown influencing the outcome of urgent restoration of patency of the respiratory pathways. Exact indications are proposed on carrying out self-locking stents in patients with malignant damage of the trachea, and the sequence of actions in patients with decompensated stenosis of the trachea of malignant nature.

[The first successful bilateral lung transplantation in Russia].

Lung transplantation is one of the most difficult fields of contemporary transplantology. The operation was performed on a 53-year-old female who had been suffering from terminal stage COPD. The period of cold ischemia for the right and left lung was 1 hour 30 minutes and 2 hours 25 minutes respectively. The total operation time was 4 hours and 40 minutes. There were no surgical complications. There were no signs of transplant rejection 6 weeks after the operation. The considerable decrease in dispnea and increase in quality of life were registered during the follow-up. FEV1 was increased by 80% and 6 minute walk test distance was increased by 200 meters.

A novel phospholipid derivative of indomethacin, DP-155 [mixture of 1-steroyl and 1-palmitoyl-2-{6-[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl acetamido]hexanoyl}-sn-glycero-3-phosophatidyl [corrected] choline], shows superior safety and similar efficacy in reducing brain amyloid beta in an Alzheimer's disease model.

Indomethacin has been suggested for the treatment of Alzheimer's disease (AD), but its use is limited by gastrointestinal and renal toxicity. To overcome this limitation, D-Pharm Ltd. (Rehovot, Israel) developed DP-155 (mixture of 1-steroyl and 1-palmitoyl-2-{6-[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl acetamido] hexanoyl}-Sn-glycero-3-phosophatidyl [corrected] choline), a lecithin derivative of indomethacin. Safety was tested by daily oral administration of DP-155 or indomethacin to rats in a dose range of 0.007 to 0.28 mmol/kg. The prevalence of gastrointestinal ulceration was significantly lower (10-fold) for DP-155 than for indomethacin, and the ulcerations were delayed. Signs of renal toxicity, namely reduced urine output and increased urine N-acetyl glycosaminidase to creatinine ratio, were 5-fold lower for DP-155. Indomethacin, but not an equimolar dose of DP-155, reduced urine bicyclo-prostaglandin E(2). An equimolar oral dose of DP-155 or indomethacin, administered every 4 h for 3 days, was equally efficacious in reducing the levels of Abeta42 in the brains of Tg2576 mice. Indomethacin was the principal metabolite of DP-155 in the serum. After DP-155 oral administration, indomethacin's half-life in the serum and the brain was 22 and 93 h, respectively, compared with 10 and 24 h following indomethacin oral administration. The brain to serum ratio was 3.5 times higher for DP-155 than indomethacin. This finding explains the efficacy of DP-155 in reducing Abeta42 brain levels, despite the low systemic blood concentrations of indomethacin derived from DP-155. In conclusion, compared with indomethacin, DP-155 has significantly lower toxicity in the gut and kidney while maintaining similar efficacy to indomethacin in lowering Abeta42 in the brains of Tg2576 mice. This superior safety profile highlights DP-155's potential as an improved indomethacin-based therapy for AD.

BRCA1-positive breast cancers in young women from Poland.

We identified 4316 unselected incident cases of early-onset breast cancers (<51 ears of age at diagnosis) in 18 Polish hospitals between 1996 and 2003. We were able to obtain a blood sample for DNA analysis from 3472 of these (80.4%). All cases were tested for the presence of three founder mutations in BRCA1. The proportion of cases with a BRCA1 mutation was 5.7%. The hereditary proportions were higher than this for women with breast cancer diagnosed before age 40 (9%), for women with cancer of medullary or atypical medullary histology (28%), for those with bilateral cancer (29%) or with a family history of breast or ovarian cancer (13%). It is reasonable to offer genetic testing to women with early-onset breast cancer in Poland.

[Age determination using peptide mapping of non-collagenous proteins in human dentin]. / Moznosti stanovení veku peptidovým mapováním nekolagenních proteinu lidského dentinu.

The submitted paper deals with possibilities of assessment of human age based on findings of stereospecific breakdown of proteins containing D-forms of aspartic acid. The stereospecificity of enzymatic breakdown assumes that after enzymatic hydrolysis peptide breakdown products with different molecular weights--the so-called peptide map--will be formed, depending how many D-aspartyl residues the protein contains. The authors proved in the submitted preliminary study in subjects of different age the formation of breakdown products of different size in non-collagenous proteins of human dentin which was hydrolyzed by protease V8 from Staphylococcus aureus.

Effect of heat stress on LPS-induced febrile response in D-galactosamine-sensitized rats.

We have previously reported that heat conditioning augments lipopolysaccharide (LPS)-induced fever in rats, which is accompanied by an accumulation of heat shock protein (HSP) in the liver and the reduction of the plasma level of tumor necrosis factor (TNF-alpha) (Kluger MJ, Rudolph K, Soszynski D, Conn CA, Leon LR, Kozak W, Wallen ES, and Moseley PL. Am J Physiol Regulatory Integrative Comp Physiol 273: R858-R863, 1997). In the present study we have tested whether inhibition of protein synthesis in the liver can reduce the effect of this heat conditioning on the LPS-induced febrile response in the rat. D-galactosamine (D-gal) was used to selectively inhibit liver protein synthesis. D-gal (500 mg/kg) or PBS as control was administered intraperitoneally 1 h before heat stress. LPS (50 microg/kg ip) was injected 24 h post-heat exposure. Treatment with D-gal blunted the febrile response to LPS. Moreover, heat-conditioned rats treated first with D-gal and subsequently with LPS demonstrated a profound fall in core temperature 10--18 h post-LPS. A significant increase of serum TNF-alpha accompanied this effect of D-gal on fever. Heat-conditioned animals receiving D-gal showed an inhibition in inducible HSP-70 in the liver. These data support the role of hepatic function in modulating the febrile response to LPS.

Response of F344 rats to inhalation of subclinical levels of sarin: exploring potential causes of Gulf War illness.

Subclinical, repeated exposures of F344 rats to sarin resulted in brain alterations in densities of chlonergic receptor subtypes that may be associated with memory loss and cognitive dysfunction. The exposures also depressed the immune system. The rat appears to be a good model for studying the effects of subclinical exposure to a nerve gas.

Role of cytochrome P-450 in endogenous antipyresis.

In previous reports, we (15, 18) and others (29) demonstrated data showing that various inhibitors of cytochrome P-450/epoxygenase augment fever in rats and mice, indicating that the enzyme may be involved in endogenous antipyresis. The aim of this study was to further test the hypothesis that the P-450-dependent epoxygenase pathway of arachidonic acid is part of the homeostatic system to control the height of fever. Sprague-Dawley rats were implanted with biotelemeters to monitor body temperature. Fever was induced by intraperitoneal injection of lipopolysaccharide (LPS; 80 microg/kg). We demonstrate that intraperitoneal administration of P-450 inducers (bezafibrate and dehydroepiandrosterone, 10 and 100 mg/kg) before LPS reduced fever in rats in a dose-dependent manner. In complementary experiments, rats were implanted with brain cannulas in addition to the biotelemeters. Various isomers of epoxyeicosanoids were administered into the lateral ventricle at doses of 0.01 to 10 microg/rat to test their influence on LPS-induced fever in rats. Four of five isomers were antipyretic in a dose-dependent manner. The most potent antipyretic isomers were 11, 12-epoxyeicosatrienoic acid (EET) followed by 14,15-EET, 8,9-EET, and 12(R) hydroxyeicosatetraenoic acid. These data support the hypothesis that the cytochrome P-450/epoxygenase pathway of arachidonate metabolism is part of the endogenous antipyretic system.

Acute and chronic nicotine exposures modulate the immune system through different pathways.

We have previously shown that T cells from rats exposed chronically to cigarette smoke or nicotine (NT) exhibit T cell anergy and decreased proliferation to T cell mitogens. Effects of chronic NT on T cell function persist for at least 2 weeks after the termination of NT treatment. Moreover, these effects of NT are causally related to the decreased Ca(2+) response to T cell receptor (TCR) ligation and constitutive activation of protein tyrosine kinase (PTK) and phospholipase C (PLC)-gamma1 activities. Acute NT treatment also suppresses the Con A-induced T cell proliferation; however, it is not known whether the mechanism(s) by which acute and chronic NT treatments inhibit T cell proliferation are identical. To evaluate this question, LEW rats were acutely treated with NT (1 mg/kg body wt) for 1, 2, or 24 h by an ip injection or implanted with constant-release miniosmotic pumps containing saline or NT (1 mg/kg body wt/day) for a 3-week chronic exposure. Inhibition of Con A-induced proliferation of peripheral blood cells (PBC) by both acute and chronic treatments was reversed by the inhibitor of nicotinic acetylcholine receptors, mecamylamine (MEC), indicating that these receptors are required for T cell proliferation. However, the effect of acute NT on the Con A response was short lived (i.e., observed at 1 and 2 h but not at 24 h after NT administration) and was seen in PBC but not in spleen cells. Unlike the chronic treatment, acute NT administration neither suppressed significantly the TCR-mediated [Ca(2+)](i) response nor did it cause the constitutive activation of PTK and PLC-gamma1 activities in blood lymphocytes. Acute, but not chronic, NT administration increased the plasma corticosterone concentration, and this increase was also inhibited by MEC. Moreover, adrenalectomy abrogated the acute but not chronic NT effects on the Con A response. Thus, the acute and chronic effects of NT on T lymphocytes are mechanistically distinct phenomena. Whereas chronic administration of NT causes T cell anergy, acute effects are primarily mediated via the activation of the hypothalamus-pituitary-adrenal axis.

Molecular mechanisms of fever and endogenous antipyresis.

This review summarizes recent studies on endogenous antipyretic mechanisms. Fever is the result of a balance between pyrogenic and cryogenic cytokines and hormones. Although there is considerable evidence that fever evolved as a host defense response, it is important that the rise in body temperature not be too high. Many endogenous cryogens or antipyretics that limit the rise in body temperature have been identified during the last 25 years. These include alpha-MSH, arginine vasopressin, glucocorticoids, TNF (under certain circumstances), and IL-10. Most recently, evidence has accumulated that cytochrome P-450 (P-450), part of the alternative pathway for arachidonic acid metabolism, plays an important role in reduction of fever and inflammation. Supporting a role for P-450 in endogenous antipyresis and antiinflammation includes evidence that (1) inducers of P-450 reduce fever, (2) inhibitors of P-450 cause a larger fever, (3) and P-450 arachidonic acid metabolites reduce fever.