Liver expression of matrix metalloproteases and their inhibitors in hepatocellular carcinoma.

BACKGROUND: Several studies have suggested the significance of some metalloproteases in the malignant behaviour of hepatocellular carcinoma. AIMS: To evaluate the liver expression of MMPs and their tissular inhibitors in patients with HCC. METHODS: An immunohistochemical study using tissue microarrays on samples obtained from 30 HCC patients, with antibodies against MMPs (1, 2, 7, 9, 11, 13 and 14) and TIMPs (1, 2 and 3) was performed. Results were correlated with various clinico-pathological findings and with overall survival. RESULTS: MMP-1 is mainly expressed by stromal cells, and MMP-13, TIMP-1 and TIMP-2 by inflammatory cells. A positive correlation between MMP-1 expression and larger size tumours (p<0.01) was found. Increased TIMP-2 expression was associated with higher preoperative serum levels of alpha-fetoprotein (p<0.01). Unsupervised hierarchical clustering for total score values designated two groups, one of them characterised by high MMPs and TIMPs expressions, including 21 cases (70%) for tumour cell clustering, 5 cases for fibroblasts (16.6%) and 6 cases for inflammatory cells (20%). All patients showing elevated MMPs and TIMPs expression in stromal cells presented a poor prognosis (p<0.05). CONCLUSIONS: High liver MMPs and TIMPs expressions in peritumour stromal cells are related to a poorer prognosis in HCC.

Levonorgestrel pharmacokinetics in plasma and milk of lactating women who take 1.5 mg for emergency contraception.

BACKGROUND: Progestin-only methods are among the contraceptive options available for breastfeeding women, however the doses of progestin used in emergency contraception (EC) have not been evaluated in nursing mothers. We therefore investigated the pharmacokinetics of 1.5 mg levonorgestrel (LNG) in lactating women. METHODS: Twelve healthy exclusively breastfeeding volunteers received 1.5 mg LNG. Women refrained from nursing for 72 h after dosing and fed their infants with milk frozen beforehand. Serial blood and milk samples were collected for 120 h and assayed for LNG and sex hormone binding globulin. RESULTS: LNG concentrations peaked in plasma and in milk 1-4 h and 2-4 h after dosing, respectively. Concentrations in milk (M) paralleled those in plasma (P) but were consistently lower (mean M:P ratio 0.28). Estimated infant exposure to LNG is 1.6 microg on the day of dosing (1 microg in the first 8 h), 0.3 microg on the second day and 0.2 microg on the third day. CONCLUSIONS: Nursing mothers may need EC. These results suggest that to limit infant exposure to the period of maximum LNG excretion in milk, mothers should discontinue nursing for at least 8 h, but not more than 24 h, after EC.

Mujer de 37 años con molestias abdominales y lesión focal esplénica / 37 year old woman with abdominal discomfort and splenic focal lesion

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Does meloxicam increase the incidence of anovulation induced by single administration of levonorgestrel in emergency contraception? A pilot study.

BACKGROUND: Levonorgestrel (LNG) consistently prevents follicular rupture only when it is given before the onset of the ovulatory stimulus. As locally synthesized prostaglandin (PG) plays a crucial role in follicular rupture and cyclooxygenase-2 (cox-2) catalyses the final step of PG synthesis, we reasoned that adding a cox-2 inhibitor to LNG would prevent follicular rupture even after the ovulatory process had been triggered by the gonadotrophin surge. METHODS: Forty-one women were divided into two groups. One was treated when the size of the leading follicle was 15-17 mm (n=10) and the other when it was >or=18 mm (n=31). Each woman contributed with one cycle treated with LNG 1.5 mg single dose plus placebo and another treated with LNG + meloxicam (Melox) 15 mg, in a randomized order. Serial blood sampling for the assay of LH and follicular monitoring by transvaginal ultrasound were performed before and after treatment. RESULTS: Follicular rupture failed to occur within the 5-day period that followed treatment in 50 and 70% of cycles treated with LNG + Placebo and LNG + Melox, respectively, in the 15-17 mm group (P=0.15) and in 16 and 39% of cycles treated with LNG + Placebo and LNG + Melox, respectively, in the >or=18 mm group (P < 0.052). The overall proportion of cycles with no follicular rupture or ovulatory dysfunction increased significantly by the addition of Melox to LNG (66 versus 88%, P < 0.012; n=41-matched pairs). CONCLUSIONS: The trend towards increased incidence of no follicular rupture when Melox was combined with LNG suggests that the addition of a cox-2 inhibitor has the potential to improve the contraceptive efficacy of LNG by a pre-fertilization effect.

Feasibility study of Nestorone-ethinylestradiol vaginal contraceptive ring for emergency contraception.

OBJECTIVE: The Nestorone/ethinylestradiol (NES/EE) vaginal ring is being developed as a regular contraceptive method by the Population Council. This ring is designed to release NES 150 microg/day and EE 15 microg/day during 1 year. Here, we report a Phase I clinical trial to determine the usefulness of this ring for emergency contraception. To that end, we tested the ability of this ring to interfere with ovulation when it is inserted during the follicular phase. METHOD: Forty-eight women protected from the risk of pregnancy by nonhormonal methods were divided into three groups, which differed by the size of the dominant follicle at the time of ring insertion: 12-14 mm (n = 16), 15-17 mm (n = 18) and >or=18 mm (n = 14) diameter. The NES/EE ring was left in the vagina for 7 consecutive days, after which it was removed. The growth of the leading follicle and plasma levels of estradiol, progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the ensuing 5 days after ring insertion were determined. Afterwards, steroid hormones were measured twice a week, until menses took place. All women had a control cycle before the ring cycle, and the range of maximum follicular diameter assigned to each volunteer was the same for the control and the ring cycle at the time when placebo was ingested or the ring inserted. RESULTS: During the 5-day period after ring insertion with follicles 12-17 mm, ovulation was absent in 25 of 34 cycles (p < .01 vs. control), and ovulatory dysfunction (absent, blunted or mistimed LH peak) occurred in 8 of the 9 remaining cycles (33/34 ovulatory processes altered; p < .005 vs. control). After ring insertion with follicles >or=18 mm in diameter, ovulation did not occur in 2 of 14 cycles or was dysfunctional in 7 of the 12 remaining cycles (9/14 ovulatory processes altered; p<.025 vs. control). Altogether, 87.5% of ring cycles (42/48) had either no ovulation or ovulatory dysfunction in the 5-day study period, in contrast to 39.6% (19/48 cycles) in control cycles (p < .001). Among follicles that failed to rupture within the 5-day study period, none ruptured later on in the ring-treated cycles, while 9 of 16 did so in control cycles. Sixty-two percent of ring-treated cycles were shorter than 24 days. Nausea, vaginal discharge and abdominal pain were the most frequently reported adverse events during ring use. CONCLUSION: Interference with 87.5% of ovulatory processes, without ovulation occurring later in the cycle and shortening of cycle length, suggests the NES/EE ring may be used as an emergency contraceptive method, with the potential advantage of providing continuing contraception after it has performed its emergency function.

Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 0.75-mg dose given on the days preceding ovulation.

We assessed to what extent the standard dose of levonorgestrel (LNG), used for emergency contraception, or a single dose (half dose), given in the follicular phase, affects the ovulatory process during the ensuing 5-day period. Fifty-eight women were divided into three groups according to timing of treatment. Each woman contributed with three treatment cycles separated by resting cycles. All received placebo in one cycle, and standard or single dose in two other cycles, in a randomized order. The diameter of the dominant follicle determined the time of treatment. Each woman had the same diameter assigned for all her treatments. Diameters were grouped into 33 categories: 12-14, 15-17 or 18-20 mm. Follicular rupture failed to occur during the 5-day period in 44%, 50% and 36% of cycles with the standard, half dose and placebo, respectively. Ovulatory dysfunction, characterized by follicular rupture associated with absent, blunted or mistimed gonadotropin surge, occurred in 35%, 36% and 5% of standard, single dose or placebo cycles, respectively. In conclusion, LNG can disrupt the ovulatory process in 93% of cycles treated when the diameter of the dominant follicle is between 12 and 17 mm. It is highly probable that this mode of action fully accounts for the contraceptive efficacy as well as the failure rate of this method. The present data suggest that half the dose may be as effective as the standard dose.

[Adrenal gland myelolipoma: radiological view]. / Mielolipoma suprarrenal: una visión radiológica.

OBJECTIVE: To report a case of adrenal myelolipoma in a female patient with a history of arterial hypertension and increased plasma aldosterone levels. METHODS: Evaluation by CT and ultrasound, and anatomopathological analysis were performed. RESULTS: The CT and ultrasound scans showed a fat-containing adrenal mass. The patient underwent surgery. Histological analysis of the surgical specimen demonstrated a myelolipoma, a benign tumor composed in varying proportions of adipose and hematopoietic tissue. CONCLUSIONS: A diagnosis of adrenal myelolipoma must be considered when a fat-containing adrenal mass is demonstrated by ultrasound, CT or MRI.

The development of circadian rhythms in the fetus and neonate.

The circadian time-keeping system is the neural system that allows predictive adaptation of individuals to the reproducible 24-hour day/night alternations of our planet. A biological clock, the suprachiasmatic nucleus, receives environmental information and imposes a circadian pattern to physiological functions. Since the suprachiasmatic nucleus develops early in gestation and circadian rhythms are present in the fetus and newborn, the circadian system seems to be functional in fetal life and can receive circadian inputs through the mother. The neonate moves to an environment in which the main time giving signal is the light:dark cycle. Teleologically, a term newborn should be fit to face this challenge. But this may be quite different for a preterm infant that trades the circadian environment to which it was previously exposed for the timeless environment of the Neonatal Intensive Care Nursery. Scientists and physicians should seek new experimental and clinical approaches to answer the challenging questions of perinatal chronomedicine.

Invaginación ileocecal causada por un pólipo fibroide inflamatorio / Ileocecal intussusception caused by an inflammatory fibroid polyp

El pólipo fibroide inflamatorio es una lesión poco frecuente del tracto gastrointestinal caracterizada por una proliferación celular no neoplásica compuesta por fibroblastos, vasos sanguíneos y células inflamatorias en el seno de una estroma edematosa y colágena. Presentamos el caso de una mujer de 78 años de edad en la que la enfermedad se manifestó inicialmente con un cuadro de suboclusión intestinal. El estudio histológico puso de manifiesto una estructura polipoide constituida por una proliferación de vasos de variado tamaño, algunos congestivos, y de fibroblastos, que se disponían en áreas de forma concéntrica. La estroma se acompañaba de un intenso infiltrado inflamatorio con abundantes eosinófilos. El pólipo fibroide inflamatorio podría considerarse una lesión no neoplásica de carácter reactivo e inflamatorio, y explicarse como una cicatrización hipertrófica del tejido conectivo submucoso, a modo de queloide (AU)

[Intestinal tuberculosis, a difficult suspected diagnosis]. / Tuberculosis intestinal, un difícil diagnóstico de presunción.

Intestinal tuberculosis (ITB) is an always difficult clinical diagnosis; we must keep in mind it in the diagnosis of patients with abdominal pain, even without concomitant lung involvement. Seven patients with ITB were revised. Five patients were male and two female, with a mean age of 45 years; all of them presented abdominal pain. Ileocecal region was involved in 71.4% of the cases. Only one patient showed old specific pulmonary lesions radiologically. Neoplasia was the most frequent clinical presumption. ITB diagnosis was made only in one case, as first possibility. Histopathological examination revealed caseous granulomas in all the cases, with acid-alcohol resistant bacilli in 71.4% of them. We want to underline the need of thinking about ITB, in the clinical evaluation of in specific abdominal pain, above all in immunosuppressed patients, and to emphasize the importance of histopathologic findings in the final diagnosis of this entity.

Tuberculosis intestinal, un difícil diagnóstico de presunción / Intestinal tuberculosis, difficult clinical diagnosis

La tuberculosis intestinal (TBI) es un diagnóstico clínico siempre difícil que es necesario tener en cuenta al valorar cuadros de dolor abdominal, incluso sin afectación pulmonar concomitante. Revisamos siete casos de TBI, en cinco varones y dos mujeres, con una edad media de 45 años; todos se presentaron como dolor abdominal. La localización pricipal fue íleo-cecal (71,4%). En un enfermo se documentó radiografía de tórax anormal por tuberculosis pulmonar antigua. El diagnóstico de presunción más frecuente fue el de neoplasia y sólo en un caso se pensó en TBI como primera posibilidad. Se llegó al diagnóstico final tras el estudio histopatológico, en el que se observaron granulomas caseificantes en todos los casos, con bacilos ácido-alcohol resistentes en el 71,4%. Queremos subrayar la necesidad de pensar en TBI, al valorar cuadros de dolor abdominal, sobre todo en inmunodeprimidos y destacar la importancia del estudio anatomopatológico en el diagnóstico final de estos enfermos (AU)

[An intimal sarcoma of the pulmonary artery. An immunohistochemical study]. / Sarcoma intimal de la arteria pulmonar. Estudio inmunohistoquímico.

Pulmonary artery intimal sarcomas tend to be presented with symptoms of pulmonary thromboembolism and grow regionally, with little capacity to metastasize. They probably originate from subendothelial cells, that become myofibroblasts. Knowledge of it is important to establish a presurgery diagnosis, with the possibility of a total resection, the only useful treatment until now. We report a case of a pulmonary artery primary sarcoma, in a 73 year old woman, admitted with hemoptysis and pleuritic chest pain, who died ten days after. Autopsy revealed an intraluminal mass at the pulmonary artery trunk, without regional nor distance involvement. Microscopic study showed a pleomorphic tumor with spindle and epithelioid cells, positive for actin, desmin and vimentin. All these data support the diagnosis of primary intimal sarcoma of the pulmonary artery. We want to emphasize the myogenic differentiation of the tumor, uncommon in previously reported cases.

[Alveolar rhabdomyosarcoma with massive infiltration of the bone marrow as its initial manifestation]. / Rabdomiosarcoma alveolar con infiltración masiva de medula ósea como manifestación inicial.

We report a case of alveolar rhabdomyosarcoma (AR) with massive infiltration of bone marrow at presentation, and initial diagnosis in bone marrow aspirate. A 35 year old man presented with a submandibular mass, and hematomas after mild traumatisms. Peripheral blood showed thrombocytopenia and a normocytic anaemia. Bone marrow film showed diffuse involvement by undifferentiated blasts with rhabdomyoblastic features. Subsequent biopsy of submandibular lymph node confirmed the diagnosis with positivity for specific muscle actin and desmin, and negativity for lymphoid markers. Initial presentation of AR with extensive bone marrow involvement is extremely rare, and it could lead to wrong diagnosis and treatment of acute leukaemia, with the serious consequences that this would have. Immunohistochemical study and morphologic differential features can be of great diagnostic help.

[Extramedullary anaplastic plasmacytoma]. / Plasmocitoma anaplásico extramedular.

A case of extramedullary plasmacytoma of the maxillary sinus, locally aggressive, in a 65 years old man is presented. Clinical diagnosis of adenocarcinoma was suspected but the pathological study showed an anaplastic morphology, with little plasmacytic differentiation and lack of stain with cytokeratins and epithelial membrane antigen (EMA), immunohistochemical marker of plasmatic cells, among others. Definitive diagnosis was based on light chain restriction and lack of multiple myeloma.

[Primary round-cell liposarcoma of the bladder]. / Liposarcoma de células redondas primario de vejiga urinaria.

OBJECTIVE: To report a rare case of primary round cell liposarcoma of the urinary bladder. METHODS: A case of primary round cell liposarcoma of the urinary bladder in an 80-year-old female with hematuria is presented. The patient had a large, solid, non-circumscribed bladder tumor of 6.5 cms. The radiological, histological and immunohistochemical findings are discussed. RESULTS: The neoplasm was composed of isolated lipoblasts among numerous small round cells that were positive for S-100 and vimentin, and a high proliferation rate was demonstrated by Ki-67. The patient died 10 months after the histologic diagnosis. CONCLUSION: Primary liposarcoma of the urinary bladder is a very rare tumor with a poor prognosis that usually presents as a large tumor mass.

[Cytological diagnosis of malignant melanoma of the esophagus]. / Diagnóstico citológico de melanoma maligno de esófago.

Malignant melanoma of the esophagus is an extremely rare neoplasm. We presented a case of this neoplasm diagnosed on a cytologic smear from a 84 year-old women. The smear was characterized by scattered dissociated cells with hyperchromatic irregular nuclei, prominent nucleoli and occasional cytoplasmic brown pigment. The immunohistochemical study revealed positivity for HMB-45 and S-100 protein.

Non-abortive effect of Adhatoda vasica spissum leaf extract by oral administration in rats.

The possible abortive effect of an extract of Adhatoda vasica leaf spissum, was studied in rats. The principal alkaloid detected in the extract was vasicine (0.85 ± 0.03%). The extract (325 mg/kg/day) was administered with a gastric cannula to a group of 5 pregnant females between day 1 and 9 of pregnancy. In another experiment 9 pregnant females received in the water 0.25 and 2.5% of Adhatoda vasica between day 1 and 9 of pregnancy. It was concluded that the administration of Adhatoda vasica did not produce abortion in any of the treated groups.