[Gadolinium-based contrast agents for magnetic resonance imaging]. / Contrastes basados en gadolinio utilizados en resonancia magnética.

Gadolinium-based contrast agents are increasingly being used in magnetic resonance imaging. These agents can improve the contrast in images and provide information about function and metabolism, increasing both sensitivity and specificity. We describe the gadolinium-based contrast agents that have been approved for clinical use, detailing their main characteristics based on their chemical structure, stability, and safety. In general terms, these compounds are safe. Nevertheless, adverse reactions, the possibility of nephrotoxicity from these compounds, and the possibility of developing nephrogenic systemic fibrosis will be covered in this article. Lastly, the article will discuss the current guidelines, recommendations, and contraindications for their clinical use, including the management of pregnant and breast-feeding patients.

Study of hemodynamic instability due to intrapelvic hemorrhage as a consequence of ilioischiopubian branch fractures in geriatric patients. / Estudio de la inestabilidad hemodinámica por hemorragia intrapélvica como consecuencia de fracturas de ramas ilio e isquiopubianas en pacientes geriátricos.

INTRODUCTION: Pelvic branch fractures are a common feature in old people which are usually treated conservatively. Massive hemorrhage is a strange complication that can compromise the patient's life. The objective of this study is to determine the incidence and possible risk factors of massive arterial injury in fractures of pelvic branches due to low energy trauma in patients over 65 years old. CLINICAL CASE: Observational study of 142 patients diagnosed with pelvic branch fracture, We analyzed the age, sex, anatomical location, hemoglobin, need for hospital admission, complementary diagnostic test, complications and hospital stay. RESULTS: All those ilioisquiopubial fractures complicated with massive bleeding (4 patients) were located in the Nakatani area I in close relationship with the obturator artery, internal pudendal artery and the Corona Mortis. All patients needed supraselective embolization for hemorrhagic control. Three of the patients were taking anticoagulants. DISCUSSION: The 2,8% of patients with pelvic branch fractures may suffer a hemorrhagic complication. Be able to establish possible risk factors such a medication or anatomical location can help us identify these patients and carry out closer surveillance.

Melatonin influences on the neuroendocrine-reproductive axis.

The neuroendocrine-reproductive axis designates the functional activity of the hypothalamus-pituitary-gonadal axis. A delicate synchronization of many inputs at these three different levels is vital for normal reproductive function. From the median basal hypothalamus, the median eminence releases gonadotrophin releasing hormone into the portal circulation to reach the anterior pituitary gland. Gonadotrophin releasing hormone is obviously a key hormone for the regulation of the secretion of gonadotrophins LH and FSH.

Ageing and melatonin influence on in vitro gonadotropins and prolactin secretion from pituitary and median eminence.

The effect of ageing and/or melatonin (MEL) on in vitro gonadotropins, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) release and tissue content from pituitary and median eminence (ME) were investigated. Gonadotropins and PRL basal release (I-1) from hemipituitaries of young cyclic-rats was decreased by MEL to levels shown in old acyclic rats. Pituitary tissue content of LH and PRL were not affected by ageing or MEL treatment. However, pituitary FSH tissue content was decreased by ageing and MEL, suggesting a different regulatory mechanism. MEL inhibitory influence on pituitary hormones is mainly exerted on the secretory process. This effect is only exerted in young rats. ME LH and PRL release and content were significantly lower than in pituitary. However, FSH release and content in ME showed values similar to those found in the pituitary. This study confirms that the functional capacities of pituitary gland and ME are maintained during reproductive senescence.

In vitro pituitary responsiveness to LHRH in young and old female rats. Influence of melatonin.

The effect of aging and melatonin on in vitro pituitary responsiveness to luteinizing hormone-releasing hormone (LHRH) was studied. Young cyclic (3-months-old) control (cyclic-control, N = 15), and melatonin (MEL) treated for 2 months (150 microg/100 g BW) (cyclic-MEL, N = 15), old acyclic (23-months-old) control (acyclic-control, N = 13), and MEL-treated (acyclic-MEL, N = 18) rats were used. The hormones analyzed were luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL). The results showed a different influence of the reproductive status as well as of melatonin on the basal secretion rate of both gonadotropins, i.e. LH and FSH. Only the basal FSH release was significantly reduced in cyclic-MEL and acyclic-controls compared to cyclic-controls. The hemipitutary FSH content raised to values similar to those observed for FSH secretion and only the cyclic-MEL group showed significantly higher FSH pituitary content than for release. LHRH addition to the incubation medium resulted in increased LH release for both cyclic and acyclic rats, but FSH release was only stimulated in acyclic rats. Melatonin treatment blunted this response in both cases. In addition, melatonin treatment inhibited prolactin release in acyclic-MEL group after LHRH stimulation but not the basal levels. Pituitary LH and prolactin contents, were significantly higher than the pituitary LH and prolactin levels released from all groups studied, and were not affected by reproductive senescence nor by exogenous melatonin. These data indicate that aging influences more the secretory than the biosynthetic processes. Melatonin influences is endocrine status-dependent, being inhibitory when pituitary hormones reach their higher values.

Developmental pattern of tachykinins during aging in several organs: effect of exogenous melatonin.

Mammalian neurokinin A (NKA) and substance P (SP) are neuropeptides widely distributed in the body; they are potential regulators of the basal blood flow and therefore of the function of many organs and tissues. In the present investigation, we studied the age-dependent changes in NKA and SP in ovary, liver, pancreas and spleen as well as the role of exogenous melatonin on these changes. Female rats of 5, 15 or 25 months of age were studied. In the ovary, NKA concentrations did not change during aging. SP concentrations in the control group were significantly higher (P<0.01) in old rats than in the other two age groups studied. Melatonin treatment resulted in reduced concentrations as compared with those of the control old rats. In the pancreas, NKA and SP concentrations increased during aging, the young rats showing significantly lower values (P<0.01) than middle-aged and old rats for NKA and significantly lower (P<0.01) than the old rats for SP. After melatonin treatment the differences in NKA concentrations disappeared and SP decreased in middle-aged as compared with those in old rats. In the liver, NKA and SP concentrations in the control and melatonin-treated groups did not differ significantly for the three age groups studied. Splenic NKA in control and melatonin-treated groups increased from young to middle-age up to old ages. SP concentrations showed similar values at all ages except in melatonin-treated old rats; in these animals there were significantly higher concentrations than in young melatonin-treated rats. The effect of melatonin was mainly observed on the ovary and pancreas in old rats, with a reduction in the concentrations as compared with those observed in the young groups.

Seasonal changes of SP and NKA in frontal cortex, striatum and testes in the rat. Role of maternal pineal gland.

The concentrations of neurokinin A (NKA) and substance P (SP), members of tachykinins family, have been studied in all seasons of the year in frontal cortex, striatum and testes of male offspring 21-, 31-, or 60 days old of mother Wistar rats: control, pinealectomized (PIN-X) and pinealectomized + melatonin during pregnancy (PIN- X + MEL) kept under 12h:12h L:D. Control-offspring: in spite of having been kept under constant environmental conditions throughout the year, had marked differences in tachykinin concentrations. The highest tachykinin concentrations in the frontal cortex were found in summer and fall and the lowest in winter and spring. Maternal PIN-X resulted in alterations of this developmental pattern, mainly in PIN-X- and PIN- X + MEL-offspring in which the highest tachykinin concentrations at 21 and 31 days of age were only observed during summer. The alterations were observed up to 60 days of age for both tachykinins, when at this age control-offspring showed similar NKA concentrations. Seasonal variations were still observed in PIN-X- and PIN- X + MEL-offspring. In striatum and testes no mayor modifications throughout the four seasons of the year were found, with very few exceptions. PIN-X did not alter tachykinin concentrations, neither treatment with melatonin did it. In conclusion, our data clearly indicate for the first time that NKA and SP do indeed have seasonal rhythms in frontal cortex and that the maternal pineal gland plays a role in their entrainment already during fetal life.

Normal frequencies of the C677T genotypes on the methylenetetrahydrofolate reductase (MTHFR) gene among lymphoproliferative disorders but not in multiple myeloma.

The folate availability seems to be critical for the DNA integrity since it is required for the transfer of methyl groups in the biosynthesis of thymidilate. Although the excessive incorporation of uracils to the DNA can be efficiently removed, this mechanism of reparation produces many double-strand breaks from two opposing nicks. Several chromosomal abnormalities (mainly translocations and deletions perhaps not well understood) are involved in the origin of lymphoproliferative disorders. The TT homozygosity at nucleotide 677 in the gene of methylene tetrahydrofolatereductase (MTHFR), a key enzyme in folate metabolism, was recently linked to a significant protection against colon carcinoma and acute lymphoblastic leukaemia in adults. We analysed the genotype frequencies of C677T-MTHFR in a group of 143 patients with lymphoproliferative disorders (REAL classification) and 200 controls. Overally, the frequencies of the polymorphic allele were similar (35.3% and 32.0% respectively)(P=0.6). We did not find differences between patients and controls except for myeloma/plasmacytoma group (n=26) which showed a CC genotype less than expected (19% vs 46%) (p=0.01) with a frequency ratio of 0.28 (0.10-0.77). Even among the IgG myeloma cases only one patient showed a common genotype (CC) (1/15, 7%) (P=0.003). If these preliminary data are validated with prospective studies, the 677C allele of MTHFR gene could be confirmed as an effective multiple myeloma protective factor (specially for the IgG cases).

Influence of maternal pineal gland on the developmental pattern of neurokinin A (NKA) and substance P (SP) in male-rat-offspring: relationship to the season of the year.

The present study examines the influence of maternal pineal gland on the frontal cortex, striatal and testicular concentrations of the tachykinins, neurokinin A (NKA) and substance P (SP). Control, pinealectomized (PIN-X) and PIN-X plus melatonin-treated (PIN-X + MEL) mother rats were prepared. Male offspring rats were studied at 21, 31 and 60 days of age, during the four seasons of the year. In control-offspring tachykinin concentrations in frontal cortex were found at their highest levels in 21-day-old rats with a moderate decrease up to 60 days of age. This developmental pattern was season-dependent, observed only during summer and fall. Maternal PIN-X or PIN-X + MEL resulted in alterations in the offspring, showing during spring and summer significantly higher concentrations (P < 0.01) and during fall significantly lower concentrations of tachykinins in the frontal cortex (P < 0.05, P < 0.01) as compared to control-offspring. The tachykinin concentration in the striatum of control-offspring showed no major modifications throughout the ages studied in the four seasons of the year. With very few exceptions, PIN-X- and PIN-X + MEL did not alter tachykinin concentrations in striatum. Testicular SP concentrations showed a decrease from 21 to 60 days of age. PIN-X or PIN-X + MEL only caused minor and inconsistent modifications in testicular SP levels. In conclusion, our data clearly indicate for the first time that the maternal pineal gland participates in the regulation of the postnatal tachykinin development in some areas of the central nervous system. This effect was more evident in the frontal cortex than in the striatum and testes.

In vitro pituitary prolactin, growth hormone and follicle stimulating hormone secretion during sexual maturation of female rats primed with melatonin.

The influence of in vivo melatonin administration on in vitro pituitary follicle stimulating hormone (FSH), growth hormone (GH) and prolactin secretion, as well as the possible influence of dopamine (DA) were evaluated in prepubertal (31-day-old), pubertal (33-day-old) and adult female rats at diestrus phase of the sexual cycle. The in vitro pituitary hormone secretions were evaluated at basal rate for the first hour of incubation only, in Krebs Ringer phosphate (KRP) (I1) and after a second hour of incubation with KRP (I2) or with KRP+DA (I2 plus DA). I1PRL secretion was significantly higher in 33-day-old control and melatonin treated (MEL) rats as compared to I2 periods. However, in 31-day-old rats I1 secretion was higher than in the I2 or I2+DA periods, in MEL rats. In vitro GH secretion was significantly higher at I1 than during I2 periods in the control 31- and 33-day-old groups, but not in MEL rats. The only significant effect of DA was the elevation of GH in prepubertal MEL rats. In vitro FSH release was increased by melatonin in 31- and 33-day-old female rats. No differences in PRL, GH and FSH secretion were found in adult rats. In conclusion, the results show that melatonin effects upon in vitro pituitary gland activity are reproductive-stage-dependent modifying the secretory capacity of the lactotrop, gonadotrop and somatotrop during prepubertal and pubertal ages but not in adult rats studied at a quiescent phase of the sexual cycle.

[Lowering high levels of fasting total homocysteine with folic acid and vitamins B in patients with venous thromboembolism: relationship between response and the C677T methylenetetrahydrofolate reductase (MTHRF) genotype]. / Reducción de concentraciones elevadas de homocisteína con ácido fólico y vitaminas B en pacientes con tromboembolia venosa: relación entre respuesta y genotipo C677T de la metilén tetrahidrofólico reductasa (MTHFR).

BACKGROUND: High levels of plasma total homocysteine (tHcy) are involved in arterial or venous occlusive diseases. It essentially depends on the nutritional status of folic acid (FA) and vitamins B12 or B6, but also on the methylenetetrahydrofolate reductase (MTHFR) enzymatic activity. We aim to evaluate the response of the hyperhomocysteinemia (HHcy) to a standard schedule of vitamin supplementation, according with the MTHFR genotype. PATIENTS AND METHODS: 227 patients, diagnosed with venous thromboembolism (VTE) were analysed for tHcy (in fasting conditions), and for the MTHFR-C677T gene polymorphism. When the tHcy exceeded the cut-off point (men = 16, women = 15 mumol/l), the patients were supplemented with a dose equivalent to 1 mg FA, 0.2 mg B12 and 100 mg of B6, daily by 6 weeks. Afterwards they were reanalysed and the reduction was stratified by MTHFR genotype, looking for any difference in the response. RESULTS: The mean fasting tHcy was 12.3 mumol/l (SD = 8). The 51 hyperhomocysteinemic patients (22%) were older (65.1 y) than the normal ones (55.0 y) (p = 0.0001). The treatment was carried out properly in 46 patients (90%). The pre-treatment mean Hcy was 23.2 (SD = 10.5) mumol/l, and it was reduced to 13.0 (SD = 5.9) (p = 0.0001) (mean reduction = 42.1%). By genotype, the C/C reduced from 21.0 to 13.2 mumol/l (37%) (n = 18), the C/T from 25.0 to 12.6 mumol/l (46%) (n = 24), and the abnormal homozygotes T/T from 22.7 to 14.5 mumol/l (39%) (n = 4), although no statistical significant differences were found. In 80% of cases (37/46), tHcy values normalised. A negative correlation (r = -0.471) (p = 0.005) was observed between age and response. CONCLUSIONS: The FA/B6/B12 based therapy reduces in a simple, quick and effective way (> 40% in 6 weeks) the pathologic tHcy levels on a VTE population and this is not influenced by the MTHFR genotype. As HHcy seems related with recurrences of venous thrombosis, we could speculate if it would be useful to analyse routinely the tHcy, attempting reduction in selected cases.

[Uveal lymphoid infiltration with systemic extension]. / Infiltración uveal linfoide con extensión sistémica.

CASE REPORT: We report the case of a patient who was surgically treated in his right eye because of an uncontrollable glaucoma and a retinal detachment without retinal break. Ultrasound and computed tomography showed diffuse choroidal thickening. During 6 years of follow-up, he developed a major ocular and orbitary invasion and bone marrow infiltration. He was treated by enucleation and chemotherapy with apparent total remission. DISCUSSION: Reactive lymphoid hyperplasia of the uvea consists of a lymphocytic proliferation that primarily involves the uveal tract. This process is regarded as a low malignant condition, but this case of late diagnosis showed a tendency to orbital and systemic extension.

[A series of 618 cases of monoclonal gammopathies of undetermined significance: predictive factors of disappearance of monoclonal component or evolution to malignant gammopathies]. / Serie de 618 casos de gammapatías monoclonales de significado indeterminado (GMSI): factores predictivos de desaparición del componente monoclonal o de evolución a gammapatías malignas.

INTRODUCTION: How to identify monoclonal gammopathies of undeterminated significance (MGUS) at risk for progression has been studied for the last years. AIMS: To study the incidence of MGUS in a region with 300,000 inhabitants and factors which associate with a) monoclonal gammopathy disappearance (transient MGUS) b) evolution to malignant gammopathy. METHODS: Study of 618 MGUS. RESULTS: Incidence: 30/40 new cases a year with increase to 70 cases a years in the latest years of study. Age and gender: 71,4 y (32-100), male/female ratio 1.4. Associated pathology: infection 328, heart diseases 249, rheumatic diseases 211, liver diseases 108, cancer 80, neuropathy 43. Monoclonal proteins: IgG 407, IgM 78, IgD 2, biclonal 16, triclonal 1; no heavy chain 21, light chain Kappa 389. Variables (mean): monoclonal component: 14 g/l, ESR 32,5, bone marrow: 5,9% plasma cells beta2-microglobulin: 2,59 mg/l, albumin: 3,1g/l, bone survey: normal 39,5%. Evolution: transient MGUS 20 cases. Time to disappearance 2,6 months (1,4-4,6). Evolution to malignant gammopathy 24 cases, time to progression 3 years (IC 1,82-4,3). RESULTS: Several factors were associatedç with malignant transformation: heavy chain IgA (p < 0,002), ESR (p < 0,001), age < 70 (p < 0,05), bone marrow percentage of plasma cells (p < 0,002) y ostheoporosis (p < 0,005). A MGUS follow up model is suggested.

[20210A mutation of the prothrombin and venous thromboembolism gene]. / Mutacion 20210A del gen de la protrombina y tromboembolismo venoso.

PURPOSE: Various genetic disorders interact with environmental factors to cause thrombotic diseases. Recently, a G to A transition at nucleotide 20210 in the prothrombin gene, has been described in association with venous thromboembolism, in Dutch population. Currently, several reports want to know the frequence of this mutation in other ethnic groups and populations. The aim of this work was to assess the prevalence rates of prothrombin mutation in both, thrombotic and healthy Spanish populations, and to estimate the associated relative risks. We described the clinical features in our series of thrombotic carriers and moreover, we compared a routine clotting test versus DNA analysis in the diagnosis of this anomaly. POPULATION, MATERIAL AND METHODS: The design was a non-matched case-control study. The involved populations were: 187 patients of venous thromboembolic diseases and 200 healthy controls. Patients and controls were genotyped and both, carriers and non-carrier patients, were analyzed by a routine prothrombin clotting assay, to determine the sensibility and specificity and optimal cut off level of the test. RESULTS: The 20210 A allele was identified in 17 patients (9.1%) and in 7 controls (3.5%), with a 2.76-fold increased risk (OR 2.76, 95% CI = 1.12-6.81), in carriers. One patient and none of the controls were homozygous. The clinical characteristics (first manifestation age or thrombotic recurrence) are similar in both, carriers and non-carriers, patient groups. The prothrombin level by a routine coagulometric method was 1.31 +/- 0.14 U/ml (95% CI = 1.24-1.38) for the 20210 A carriers, whereas for the non carrier-patients was significantly lower, 1.06 (95% CI = 1.03-1.08) (p < 0.00001). With a cut off level of 1.25 U/ml, 12/16 (75%) carriers and 14/132 (10.6%) non-carriers were positive. Therefore, the sensibility was 75% and the specificity 89.4%. With a cut off level of 1.40 U/ml the diagnostic efficiency was even worse. CONCLUSIONS: 3.5% of healthy subjects and 9.1% of thromboembolic patients carried this prothrombin mutation with a relative risk of 2.76 (95% CI = 1.12-6.81). The relevant clinical features are similar to the rest of the series. The mean prothrombin level was higher (1.31 U/ml) than in the normal patients (1.06 U/ml), but the clotting test seems inappropriate for a diagnostic purpose.

A patient homozygous for mutation 20210A in the prothrombin gene with venous thrombosis and transient ischemic attacks of thrombotic origin.

It is well established that genetic disorders interact with environmental factors to cause thrombotic diseases. Therefore, antithrombin, protein C, protein S deficiencies and the more recently described factor V Leiden and prothrombin mutations are currently been investigated to explain some thrombophilic states. We report the case of a 63-year-old man who developed two transient ischemic attacks and two years later an extensive femoro-iliac venous thrombosis. He was genotyped as FV R506Q negative and FII G20210A positive in homozygous state (FII 20210AA).

[Spinal cord infarction and recurrent venous thrombosis in association with estrogens and the 20210A allele of the prothrombin gene]. / Mielopatía aguda isquémica y trombosis venosa recurrente asociada a estrógenos y alelo 20210A del gen de la protrombina.

The acute spinal cord infarction is a rare cause of acute-onset paraplegia. Furthermore, it is specially uncommon that the infarction occurs in patients with apparent low predisposition to vascular disease. The 20210A allele of the prothrombin gene (causing a threefold-increased risk in venous thromboembolism) was recently associated with unexplained spinal cord infarction in young women under treatment with estrogens (contraceptive pill). We report a case of anterior spinal artery syndrome resulting from an ischaemic infarction at the anterior aspect of the spinal cord in a healthy 50-year-old woman, carrying this mutation, being the first published case under treatment with transdermal estradiol. She referred the typical sudden-onset back pain associated to clinical anterior spinal artery syndrome with sphincter dysfunction and nontraumatic paraplegia. A possible multiple sclerosis was ruled out and the steroids or immunoglobulin therapy induced no clinical improvement. Cerebrospinal fluid and other investigations were all negative. Sequential MRI scans revealed development of spinal cord infarction from T10 to T11, with increased signal in T2-weighted image (T2). Because she referred a previous thrombophlebitis and suffered a deep-vein thrombosis one month after paraplegia, a complete coagulation study was performed. Antithrombin, proteins C and S, homocysteine, factor V Leiden, lupus anticoagulant and anticardiolipin antibodies were all normal or negatives. In opposite, the 20210A variation was positive (heterozygous) and the factor VIIIc level was very high (280 U/dl eight months later). We argue the relative importance of both findings. The patient had no a substantial recovery over a period of 20 months.Certainly, the prothrombin 20210A seems to be associated with unexplained ischemic myelopathy among the young women with estrogens.