Síndrome de Behçet como diagnóstico diferencial de las úlceras genitales / Behçet's syndrome: Differential diagnosis with genital ulcers

La presencia de una úlcera genital inespecífica es el signo guía de diversas entidades clinicopatológicas. Las enfermedades de transmisión sexual son la causa más frecuente y conocida. Sin embargo, las úlceras genitales además de origen infeccioso pueden ser manifestación de una neoplasia, o de una enfermedad sistémica con afectación genital, como el síndrome de Behçet, que incluye en sus criterios diagnósticos las úlceras genitales recidivantes. Presentamos el caso de una paciente diagnosticada de síndrome de Behçet, entidad a considerar ante un cuadro de úlceras genitales de repetición

A nonspecific genital ulcer can be the first manifestation of several diseases. The best-known and most frequent cause of these ulcers is sexually transmitted diseases. Nevertheless, genital ulcers can also be a manifestation of a neoplasm or a systemic disease with genital involvement, such as Behc¸et syndrome, in which one of the diagnostic criteria is relapsing genital ulcers. We present the case of a patient diagnosed with Behc¸ et’s syndrome, an entity that should be included in the differential diagnosis of patients with recurrent genital ulcers

Torsión anexial bilateral en la posmenopausia / Bilateral adnexal torsion in the postmenopause

La torsión anexial es una complicación relativamente frecuente de las masas anexiales que se presenta sobre todo en edad reproductiva. Su diagnóstico es complicado y habitualmente definitivo tras intervención quirúrgica. Presentamos el caso de una torsión bilateral de ovario en una paciente posmenopáusica que consulta por dolor abdominal súbito. Tras laparotomía se descubren 2 cistoadenomas serosos, el mayor de 26cm, con ambos anejos torsionados. Se realiza histerectomía subtotal más doble anexectomía resolviendo el cuadro clínico de la paciente (AU)

Adnexal torsion is a relatively common complication of adnexal masses that occur mainly in reproductive age. Diagnosis is difficult and the definitive diagnosis is usually established after surgery. We report a case of bilateral ovarian torsion in a post-menopausal woman who complained of sudden abdominal pain. After laparotomy, two serous cystadenomas were discovered, the largest measuring 26cm. Both adnexa were twisted. Subtotal hysterectomy and bilateral oophorectomy was performed, producing symptom resolution (AU)

Metástasis pélvicas de cáncer de mama: revisión de cuatro casos / No disponible

La pelvis es una localización infrecuente de metástasis de cáncer de mama siendo los ovarios el sitio de afectación más común. El diagnóstico y tratamiento de las masas pélvicas de un cáncer de mama es difícil y a menudo una manifestación de la progresión metastásica de la enfermedad. En pacientes con antecedentes de cáncer de mama, la laparoscopia exploratoria parece ser la vía de elección para el diagnóstico histológico y valoración de la resecabilidad de las lesiones. Presentamos cuatro casos de metástasis de cáncer de mama en ovarios y útero y se discute el comportamiento, tratamiento y evolución de las pacientes con metástasis pélvicas(AU)

The pelvis is an uncommon metastatic site for breast cancer and the ovarian origin is the common site. The diagnosis and treatment of pelvic masses from a metastatic breast cancer are difficult and often a manifestation of metastatic progression in a patient with a known history of breast cancer. In patients with history of breast cancer, laparoscopy seems to be the preferred technique to establish the histological diagnosis and to assess the resectability of the lesions. We present four cases of metastatic breast cancer in the pelvis to the uterus and ovarian and discuss the treatment and prognosis of the patients with pelvic metastasis(AU)

Leiomiosarcoma uterino: tumoración abdominal de rápido crecimiento / Uterine leiomyosarcoma: a rapidly-growing abdominal tumor

Los sarcomas son el grupo de neoplasias uterinas menos frecuente. El propósito del caso que presentamos es tener en cuenta estos tumores en el diagnóstico diferencial de una paciente con masa abdominal de rápido crecimiento y síndrome constitucional. Esto permitirá un diagnóstico temprano y una estadificación quirúrgica adecuada, que podría ser curativa en etapas tempranas de la enfermedad (AU)

Uterine sarcomas are the least frequent group of uterine neoplasms. The aim of this case report is to serve as a reminder of the importance of including these tumors in the differential diagnosis of women with a rapidly-growing abdominal mass and constitutional syndrome. Bearing these tumors in mind could allow early diagnosis and appropriate surgical staging. Surgery can be curative in the early stages of the disease (AU)

Tumores uterinos con componente sarcomatoso: análisis retrospectivo de 18 casos / Uterine sarcomas: A retrospective analysis of 18 cases

Resumen Los sarcomas uterinos son tumores malignos del cuerpo uterino de clasificación histológica heterogénea y poco frecuentes. Suelen diagnosticarse en mujeres posmenopáusicas y tras el estudio de la pieza quirúrgica. Objetivos Revisar las características clínicas, procedimientos diagnósticos empleados, tratamiento y evolución de sarcomas uterinos en una serie de casos a 5 años. Material y métodos Se realizó un estudio descriptivo y retrospectivo de 18 casos de sarcomas uterinos diagnosticados y tratados en el Complexo Hospitalario de Pontevedra entre octubre de 2002 y diciembre de 2007. Analizamos la edad más frecuente de presentación, paridad, estudio premenopáusico y posmenopáusico, patologías asociadas, tipo histológico más prevalente, clínica más habitual, métodos diagnósticos empleados, estadios patológicos, tratamientos efectuados y seguimiento de las pacientes. Resultados La edad media global fue de 64,22 años. La nuliparidad se observó sólo en el 11,1%. El 66,6% eran posmenopáusicas. La patología médica asociada a mayor frecuencia fue la hipertensión arterial, en un 50% de los casos. El tumor más prevalente fue el carcinosarcoma, en el 33,3% de casos. El síntoma principal fue la menorragia, presente en un 61,11% de los casos, seguida del dolor abdominal, en un 22,2% de los casos. El 66,6% de las pacientes presentaba una tumoración abdominopélvica en la exploración y el 94% presentaba un valor normal del marcador tumoral CA 125. El diagnóstico definitivo se estableció por el análisis de la pieza operatoria en 13 casos (72,2%). Al 88,8% de las pacientes se las sometió a tratamiento (..) (AU)

Abstract Uterine sarcomas are a rare form of endometrial cancer with heterogeneous histologic classification. These tumors are usually diagnosed in postmenopausal women and the diagnosis is often postoperative. Objectives To review the clinical features, diagnostic procedures, treatment and outcomes of uterine sarcomas in a series of cases over a 5-year period. Material and methods We performed a retrospective descriptive study of 18 patients with uterine sarcoma diagnosed and treated in Pontevedra Hospital between October 2002 and December 2007. The following variables were analyzed: the most frequent age at presentation, parity, pre- or postmenopausal status, associated diseases, most prevalent histologic type, principal symptoms, diagnostic methods used, pathological stages, treatment, and follow-up. Results The overall mean age was 64.22 years. Nulliparity was observed in only 11.1% and 66.6% were postmenopausal. The most frequent medical disorder was hypertension in 50% of the patients. The most prevalent histological type was malignant mixed mesodermal tumor in 33.3%. The principal symptom was metrorrhagia in 61.11%, followed by abdominal pain in 22.2%. On pelvic examination, the uterus was enlarged in 66.6% of the patients and 94% showed normal serum CA 125 levels. The definitive diagnosis was established by histopathologic analysis of the surgical specimen in 13 patients (72.2%). Treatment consisted of surgery in 88.8%. Adjuvant treatment (chemotherapy, radiotherapy or hormonotherapy) was used in 77.7%. The 5-year survival rate was 22.22% in our series of cases and all four survivors had low-grade endometrial stromal sarcomas. Conclusions A high percentage of the patients underwent surgery without a correct diagnosis, frequently leading to incomplete surgery. As expected, most women with advanced-stage tumors died from the disease. Even in the early stages, this type of tumor is aggressive and has a poor prognosis (AU)

Tratamiento mediante conización de la neoplasia cervical intraepitelial en el Complejo Hospitalario de Pontevedra / Conization of cervical intraepithelial neoplasm in the pontevedra hospital complex

Objetivo Evaluar la conización como tratamiento de la neoplasia cervical intraepitelial (CIN), complicaciones y seguimiento posterior. Material y métodos Estudio retrospectivo de 79 pacientes con diferentes grados de CIN tratadas mediante conización desde el 1 de enero de 2004 hasta el 31 de diciembre de 2006. Controles a los 6 y 12 meses. Resultados La edad media fue de 37,7 años y la indicación más frecuente lesión intraepitelial cervical de grado alto (H-SIL, del inglés high grade squamous intraepithelial lesion). Medios empleados: asa de diatermia (49,36%), aguja electroquirúrgica (35,44%) y bisturí frío (15,19%). La determinación de ácido desoxirribonucleico-virus del papiloma humano resultó positiva en 72 pacientes. Cinco pacientes presentaron hemorragia postoperatoria. El estudio anatomopatológico del cono fue H-SIL en el 86%, con márgenes libres en un 88,3%. Al año de la conización, 3 pacientes presentaban persistencia de la enfermedad. Conclusiones La conización cervical como tratamiento escisional de las lesiones cervicales intarepiteliales es una técnica sencilla, efectiva, con escasas complicaciones y que permite un buen estudio anatomopatológico de la pieza quirúrgica obtenida (AU)

Objectives To evaluate conization as a treatment of cervical intraepithelial neoplasm (CIN), as well as complications and subsequent follow-up. Material and methods A retrospective study was performed in 79 patients with distinct grades of CIN treated with conization from 1st January 2004 to 31st December, 2006. Follow-up visits were made at 6 and 12 months. Results The mean age of the patients was 37.7 years and the most common indication was high-grade squamous intraepithelial lesion (H-SIL). Conization was performed by diathermy loop in 49.36%, electrosurgical needle in 35.44% and cold-knife in 15.19%. Human papilloma virus (HPV)-DNA determination was positive in 72 patients. Postoperative bleeding occurred in five patients. Histopathological analysis of the cone revealed H-SIL in 86%, with free margins in 88.3%. At 1 year after conization, persistent disease was found in three patients. Conclusions Cervical conization as a means of excising CIN is a simple and effective technique with few complications that allows correct histopathological analysis of the surgical specimen (AU)

Tetanus neurotoxin-insensitive vesicle-associated membrane protein localizes to a presynaptic membrane compartment in selected terminal subsets of the rat brain.

Tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) is a vesicular soluble N-ethyl maleimide-sensitive fusion protein attachment protein receptor (SNARE) that has been implicated in neurite outgrowth. It has previously been reported that TI-VAMP is localised in the somatodendritic compartment of neurons indicating a role in membrane fusion events within dendrites. Using a newly produced monoclonal antibody to TI-VAMP that improves signal/noise immunodetection, we report that TI-VAMP is also present in subsets of axon terminals of the adult rat brain. Four distinctive populations of labelled axon terminals were identified: 1) the hippocampal mossy fibres of the dentate gyrus and of CA3, 2) the striatal peridendritic terminal plexuses in the globus pallidus (GP), substantia nigra pars reticulata (SNr), 3) peridendritic plexuses in the central nucleus of the amygdala, and 4) the primary sensory afferents in the dorsal horn of the spinal cord. The presynaptic localisation of TI-VAMP in these locations was demonstrated by co-localisation with synaptophysin. Ultrastructural studies showed TI-VAMP labelling over synaptic vesicles in the mossy fibres, whereas it was localised in tubulo-vesicular structures and multivesicular bodies in the pyramidal cell dendrites. The presynaptic localisation of TI-VAMP occurred by P15, so relatively late during development. In contrast, dendritic labelling was most prominent during the early post-natal period. Co-localisation with markers of neurotransmitters showed that TI-VAMP-positive terminals are GABAergic in the GP and SNr and glutamatergic in the mossy fibre system and in the dorsal root afferents. Most of these terminals are known to co-localise with neuropeptides. We found met-enkephalin-immunoreactivity in a sizeable fraction of the TI-VAMP positive terminals in the GP, amygdala, and dorsal horn, as well as in a few mossy fibre terminals. The function of TI-VAMP in subsets of mature axon terminals remains to be elucidated; it could participate in the exocytotic molecular machinery and/or be implicated in particular growth properties of the mature axon terminals. Thus, the presence of TI-VAMP in the mossy fibres may correspond to the high degree of plasticity that characterises this pathway throughout adult life.

A common exocytotic mechanism mediates axonal and dendritic outgrowth.

Outgrowth of the dendrites and the axon is the basis of the establishment of the neuronal shape, and it requires addition of new membrane to both growing processes. It is not yet clear whether one or two exocytotic pathways are responsible for the respective outgrowth of axons and dendrites. We have previously shown that tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) defines a novel network of tubulovesicular structures present both at the leading edge of elongating dendrites and axons of immature hippocampal neurons developing in primary culture and that TI-VAMP is an essential protein for neurite outgrowth in PC12 cells. Here we show that the expression of the N-terminal domain of TI-VAMP inhibits the outgrowth of both dendrites and axons in neurons in primary culture. This effect is more prominent at the earliest stages of the development of neurons in vitro. Expression of the N-terminal domain deleted form of TI-VAMP has the opposite effect. This constitutively active form of TI-VAMP localizes as the endogenous protein, particularly concentrating at the leading edge of growing axons. Our results suggest that a common exocytotic mechanism that relies on TI-VAMP mediates both axonal and dendritic outgrowth in developing neurons.

Recycling of the insulin-sensitive glucose transporter GLUT4. Access of surface internalized GLUT4 molecules to the perinuclear storage compartment is mediated by the Phe5-Gln6-Gln7-Ile8 motif.

The insulin-sensitive glucose transporter GLUT4 is translocated to the plasma membrane in response to insulin and recycled back to the intracellular store(s) after removal of the hormone. We have used clonal 3T3-L1 fibroblasts and adipocyte-like cells stably expressing wild-type GLUT4 to characterize (a) the intracellular compartment where the bulk of GLUT4 is intracellularly stored and (b) the mechanisms involved in the recycling of endocytosed GLUT4 to the store compartment. Surface internalized GLUT4 is targeted to a large, flat, fenestrated saccular structure resistant to brefeldin A that localized to the vicinity of the Golgi complex is sealed to endocytosed transferrin (GLUT4 storage compartment). Recycling of endocytosed GLUT4 was studied by comparing the cellular distributions of antibody/biotin tagged GLUT4 and GLUT4(Ser(5)), a mutant with the Phe(5)-Gln(6)-Gln(7)-Ile(8) inactivated by the substitution of Ser for Phe(5). Ablation of the Phe(5)-Gln(6)-Gln(7)-Ile(8) inhibits the recycling of endocytosed GLUT4 to the GLUT4 store compartment and results in its transport to late endosomes/lysosomes where it is rapidly degraded.

Distinct reading of different structural determinants modulates the dileucine-mediated transport steps of the lysosomal membrane protein LIMPII and the insulin-sensitive glucose transporter GLUT4.

Leucine-based motifs mediate the sorting of membrane proteins at such cellular sites as the trans-Golgi network, endosomes, and plasma membrane. A Leu paired with a second Leu, Ile, or Met, while itself lacking the ability to mediate transport, is the key structural feature in these motifs. Here we have studied the structural differences between the leucine-based motifs contained in the COOH tails of LIMPII and GLUT4, two membrane proteins that are transported through the secretory pathway and are targeted to lysosomes () and to a perinuclear compartment adjacent to the Golgi complex (), respectively. LIMPII and GLUT4 display negatively (Asp(470)/Glu(471)) and positively (Arg(484)/Arg(485)) charged residues, respectively, at positions -4 and -5 upstream from the critical Leu residue. The change in the charge sign of residues -4 and -5 results in missorting of LIMPII and GLUT4. We note that the acidic Glu residue at position -4 is critical for efficient intracellular sorting of LIMPII to lysosomes, but is dispensable for its surface internalization by endocytosis. Efficient intracellular sorting and endocytosis of GLUT4 require an Arg pair between positions -4 and -7. These results are consistent with the existence of distinct leucine-based motifs and provide evidence of their different readings at different cellular sites.

Role of tetanus neurotoxin insensitive vesicle-associated membrane protein (TI-VAMP) in vesicular transport mediating neurite outgrowth.

How vesicular transport participates in neurite outgrowth is still poorly understood. Neurite outgrowth is not sensitive to tetanus neurotoxin thus does not involve synaptobrevin-mediated vesicular transport to the plasma membrane of neurons. Tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) is a vesicle-SNARE (soluble N-ethylmaleimide-sensitive fusion protein [NSF] attachment protein [SNAP] receptor), involved in transport to the apical plasma membrane in epithelial cells, a tetanus neurotoxin-resistant pathway. Here we show that TI-VAMP is essential for vesicular transport-mediating neurite outgrowth in staurosporine-differentiated PC12 cells. The NH(2)-terminal domain, which precedes the SNARE motif of TI-VAMP, inhibits the association of TI-VAMP with synaptosome-associated protein of 25 kD (SNAP25). Expression of this domain inhibits neurite outgrowth as potently as Botulinum neurotoxin E, which cleaves SNAP25. In contrast, expression of the NH(2)-terminal deletion mutant of TI-VAMP increases SNARE complex formation and strongly stimulates neurite outgrowth. These results provide the first functional evidence for the role of TI-VAMP in neurite outgrowth and point to its NH(2)-terminal domain as a key regulator in this process.

Intracellular targeting and retention of the glucose transporter GLUT4 by the perinuclear storage compartment involves distinct carboxyl-tail motifs.

The mechanisms by which the insulin-sensitive glucose transporter, GLUT4, is targeted and retained in a storage compartment near to the Golgi complex are poorly understood. Here we report that removal of the carboxyl-terminal acidic Pro(505)AspGluAsnAsp(509) sequence prevents the storage of GLUT4 in the VAMP-2 positive compartment adjacent to the Golgi complex (GSC), and results in its targeting to GLUT4-positive vesicles and Rab7-positive late endosomes. Storage of the truncated GLUT4 in the GSC is restored by substitution of Phe for the Tyr(502) residue adjacent to Pro(505) or by treatment of cells with the tyrosine kinase inhibitor genistein. Ablation of the Leu(489)Leu(490)-based motif prevents the targeting of GLUT4delta5 to GLUT4-positive-vesicles and late endosomes as well as the retention of GLUT4delta5Phe(502 )by the GSC. These results are consisting with a model of GLUT4 transport in which the targeting of the protein from the TGN to the GSC is mediated by the Leu(489)Leu(490)-based motif and its release from the GSC involves Tyr(502 )and the adjacent carboxyl-terminal Pro(505)AspGluAsnAsp(509) sequence.

[Findings on the occurrence of complications caused by DEV and HDVC (delta) vaccines]. / Rilievo della incidenza delle complicanze da vaccini DEV e HDCV (delta).

The complications arising from two different anti-rabies vaccines were compared: DEV (duck embryo vaccine; the schedule included 14 daily doses plus 3 boosters) and HDCV (human diploid cells vaccine; the schedule included 5 doses plus 1 booster). 2646 patients were immunised, following a post-exposure prophylaxis, at the Antirabies Unit of the Institute of Hygiene of Rome. Among the 1434 patients immunised with DEV, 364 (25.38%) developed side-effects, whilst among the 1212 subjects immunised with HDCV only 47 (3.88%) developed side-effects. Using DEV the more frequent complications were as follows: fever (48.62%), regional adenopathy (49.45%), erythema (89.29%), local induration (41.48%). Using HDCV the main complication was fever (65.96%). The principal association of complication in DEV were: erythema + induration + edema + adenopathy + fever; general malaise + asthenia + adenopathy; dizziness + headache. Hyperthermia resulted often associated with regional adenopathy and the general malaise with the headache in the vaccinated with HDCV. All complications were widely distributed during the period of immunisation. However most side-effects arose following the 5th DEV dose or the 2nd HDCV dose. Regional adenopathy, was the more persistent and less tolerated symptom, also local erythema showed a long persistence, whilst the other symptoms regressed within 48-72 hours with proper therapy and rest. Sex and age did not influence the incidence nor the type of complications. Neither neuroparalysis was detected nor serious impairment of health. In our study the coincidence of unwanted effects, following an antirabies immunisation, seems lower than that described in the literature. This was probably due to the high level of purification of the vaccine and possibly to the different recording of the minor symptoms.

[Effect of previous anti-rabies treatment with Fermi type vaccine on the antibody response to one dose of HDCV]. / Influenza di pregressi trattamenti antirabbici con vaccino tipo Fermi sulla risposta anticorpale ad una dose di HDCV.

We report the effect of previous anti-rabies treatments following a single HDCV challenge. The aim is to obtain guidelines for the re-vaccination of patients previously already immunised. 37 adults at risk for rabies, vaccinated 5-10 years before using a Fermi vaccine, were challenged with a single HDCV dose. 29 adults, previously not immunised were used as a control. Neutralizing antibodies' titres (indirect fluorescent antibody microtest) were monitored on day 0 (HDCV challenge) and 15. The best group produced an optimal response to the antigenic challenge: all subjects reached responses higher than the serum-conversion limit (0.5 U.I./ml), and 43.2% of patients had titres higher than 8 I.U./ml. Neither the number of previous injections of antirabies vaccine (5, 15, 20), nor the years between the first and the second vaccination were related to the antibody response. In the control group the serum-conversion limit was obtained in 31% of patients, and only 13.8% of them produced titres higher than 0.5 U.I./ml. Our data support a short vaccination schedule for patients at risk, who had an history of vaccination. In agreement with nerve-tissue vaccines, specific World Health Organisation Committee (1984), and in our researches of Fermi type, we suggest that in patients having an history of vaccination (documented by antibody titres), a single HDCV dose, monitoring the antibody response, is sufficient to control a new, not dangerous infection (site and type of the wound, animal, local epidemiology). Patients without a laboratory documentation of the previous antibody titres, or patients with a dangerous infection, should be challenged with three HDCV doses on day 0, 3, 7.