Embolización de arterias uterinas en el tratamiento de miomas uterinos sintomáticos / Uterine artery embolization for symptomatic uterine fibroids

Los miomas uterinos pueden ser causa de menstruaciones abundantes y prolongadas, de síntomas por compresión de órganos vecinos e infertilidad. La embolización de arterias uterinas es una terapia mínimamente invasiva que se ha constituido en una alternativa terapéutica a la histerectomía y la miomectomía múltiple, para el tratamiento de miomas uterinos sintomáticos, en mujeres que no desean fertilidad futura. Esta consiste en ocluir ambas arterias uterinas mediante partículas, con el objetivo de producir infarto isquémico de los miomas, y con ello, reducir su tamaño y controlar los síntomas. La presente comunicación muestra una de las primeras pacientes tratadas con esta técnica en nuestro país, con éxito en el control de síntomas de sangrado genital y compresión vesical, con seguimiento de un año.

Uterine fibroids may cause menorrhagia, infertility and a pressure effect over other pelvic organs. Uterine artery embolization (UAE) is a minimally invasive technique for treating fibroids. It has become a therapeutic alternative to hysterectomy and multiple myomectomy, for the treatment of symptomatic uterine fibroids in women do not wishing maintain their fertility. This technique consist in occluding both uterine arteries injecting small particles to cause infarction of fibroids, reducing their size and control bleeding and mass symptoms. This communication presents one of the first cases treated in our country by UAE with good symptoms control at one year follow-up.

PEN-2 gene mutation in a familial Alzheimer's disease case.

Genetic evidence indicates a central role of cerebral accumulation of beta-amyloid (Abeta) in the pathogenesis of Alzheimer's disease (AD). Beside presenilin 1 and 2, three other recently discovered proteins (Aph 1, PEN 2 and nicastrin) are associated with gamma-secretase activity, the enzymatic complex generating Abeta. Alterations in genes encoding these proteins were candidates for a role in AD. The PEN 2 gene was examined for unknown mutations and polymorphisms in sporadic and familial Alzheimer patients. Samples from age-matched controls (n=253), sporadic AD (SAD, n=256) and familial AD (FAD, n=140) were screened with DHPLC methodology followed by sequencing. Scanning the gene identified for the first time a missense mutation (D90N) in a patient with FAD. Three intronic polymorphisms were also identified, one of which had a higher presence of the mutated allele in AD subjects carrying the allele epsilon4 of apolipoprotein E than controls. The pathogenic role of the PEN-2 D90N mutation in AD is not clear, but the findings might lead to new studies on its functional and genetic role.

Quantitative ultrasound measurements of the calcaneus in the prediction of lumbar spine degeneration.

A cross-sectional study was conducted to evaluate the possible use of a low-cost radiation-free technique in the prediction of degenerative changes in the lumbar spine. Although an inverse correlation between osteoporosis and degenerative changes in the lumbar spine has been reported, no previous studies have asked whether there is a correlation between calcaneal quantitative ultrasound results and degenerative findings in the lumbar spine. In 117 patients with low back pain or pain in the lower limb, ultrasonographic parameters (speed of sound, broadband ultrasound attenuation, stiffness) of the calcaneus were correlated with evidence of degenerative changes and stenosis on magnetic resonance scans of the lumbar spine. Linear and logistic regression, as well as receiver operator characteristic curve analyses, were used to evaluate the correlation. Lumbar spine stenosis was associated with elevated calcaneal ultrasonographic parameters, particularly speed of sound. For the identification of a narrowing of the lumbar spinal canal below 100 mm(2) of dural sac cross-sectional area, speed of sound showed 89% sensitivity and 75% specificity in males older than 60 years. In male patients, we also found a significant positive correlation between ultrasonographic parameters and scores on a degenerative scale that primarily reflects intervertebral disc degeneration ( P=0.019 for speed of sound; P=0.039 for stiffness). In conclusion, calcaneal quantitative ultrasound is frequently used in elderly patients with low back pain as a diagnostic test for osteoporosis. The incidental finding of high values on ultrasonographic parameters in these subjects, particularly in males, is highly correlated with lumbar spine degeneration and stenosis, and can help to identify those symptomatic patients needing more extensive diagnostic testing.

The distally based superficial sural flap: our experience in reconstructing the lower leg and foot.

The treatment of soft-tissue defects of the lower third of the leg and foot is often an awkward problem to tackle because of the frequent involvement of muscle, tendon, and bone, which is caused by the thinness and poor circulation of the skin covering them and by the small quantity of local tissue available for reconstruction. The authors present their experience with the use of sural flaps for the treatment of small- and medium-size defects of the distal region of the lower limb. The flap used was a distally based fasciocutaneous flap raised in the posterior region of the lower two thirds of the leg. Vascularization was ensured by the superficial sural artery, which accompanies the sural nerve together with the short saphenous vein. The authors treated 18 patients (12 men and 6 women) from May 1997 to August 1999 at the Division of Plastic Surgery, University of Turin, Italy. Superficial necrosis without involvement of the deep fascia (which was grafted 1 month later) occurred in 1 patient of the 18 treated. In another 2 patients, defects were found in the flap margins, but no additional surgical revision was necessary, and recovery occurred by secondary intention. In every patient the sural flaps provided good coverage of the defects, both from a functional and an aesthetic point of view. The major advantages of this flap are its easy and quick dissection. Because the major arterial axis is not sacrificed, this flap can be used in a traumatic leg with damaged major arteries.

Factors influencing the outcome of degenerative lumbar spinal stenosis.

The objective of this study was to evaluate the influence of decreased dural sac cross-sectional area and baseline clinical parameters on the outcome of patients treated surgically or conservatively for lumbar spinal stenosis. Computed tomography or magnetic resonance imaging scans of 37 patients were digitized and the dural sac cross-sectional area was calculated. This parameter and baseline clinical, socioeconomic, and anthropometric data of the patients were correlated with 1-year and 2-year follow-up data. The decrease in dural sac cross-sectional area negatively affected walking capacity on follow-up controls in patients treated conservatively, whereas such a relation was not observed among surgically treated patients. Female sex was the main parameter that worsened the global outcome of degenerative lumbar spinal stenosis, particularly after surgical treatment.

Hypoxia augments cytokine (transforming growth factor-beta (TGF-beta) and IL-1)-induced vascular endothelial growth factor secretion by human synovial fibroblasts.

Vascular endothelial growth factor (VEGF) is abundant in synovium and synovial fluids, where it probably contributes to vascular permeability and angiogenesis in arthritic joints. To investigate the probable sources of VEGF in synovium, we compared the ability of several cytokines (TGF-beta, platelet-derived growth factor (PDGF), IL-1, tumour necrosis factor (TNF), basic fibroblast growth factor (bFGF) that are associated with arthritis and angiogenesis, to stimulate secretion of VEGF protein by human synovial fibroblasts. TGF-beta was the strongest inducer of VEGF secretion; six times more VEGF was secreted when cells were stimulated by TGF-beta than when stimulated by PDGF or IL-1 for 24 h. TNF-alpha and bFGF did not stimulate any secretion of VEGF. The stimulatory effects of TGF-beta and IL-1 on VEGF secretion were additive. Hypoxic culture alone also stimulated VEGF secretion, but more importantly, hypoxic culture conditions doubled the rate of VEGF secretion stimulated by the cytokines TGF-beta and IL-1. When dermal and synovial fibroblasts were stimulated identically by hypoxia and cytokines (TGF-beta and IL-1), synovial fibroblasts secreted four times more VEGF than did dermal fibroblasts. Thus in rheumatoid arthritis, the capacity of synovial fibroblasts in the hypoxic environment to secrete large amounts of VEGF in response to cytokines such as TGF-beta probably contributes significantly to angiogenesis in the synovium.

[Our experience with a new material for skin graft areas]. / La nostra esperienza su un nuovo materiale da medicazione per le aree di prelievo cutaneo.

The authors describe a new method of medicating disepidermised areas from which a dermo-epidermic graft has been removed to cover burn areas or following post-traumatic loss of substance. This method consists of the use of a thin microfibrillar film of a polysaccharidic type, which serves as a temporary substitute for the skin, offering selective permeability, the possibility of transpiration and gaseous exchange, but at the same time being impermeable to liquids and microorganisms. A study was performed to evaluate the efficacy and tolerability of this new dressing, involving 30 patients of both sexes aged between 9 and 87 years old. The site, dimensions, and type of graft were assessed in each patient together with the duration of pain and the time taken for the lesion to heal. This study has highlighted the positive function performed by medication with microfibrillar film in facilitating the cicatricial process, achieving complete re-epithelisation within an average of 8-9 days, with a considerable reduction in pain and satisfactory esthetic and functional result. No collateral effects or complications relating to the use of this material are reported in any of the cases studied.

Collagen-induced arthritis as a model of rheumatoid arthritis.

Collagen-induced arthritis (CIA) is an animal model for the human autoimmune disease rheumatoid arthritis (RA). CIA can be induced in several species including primates by immunization with heterologous type-II collagen (CII). Polyclonal antibodies are formed upon immunization with CII that exhibit a broad range of epitope specificities (some that cross-react with hose CII); however, only antibodies directed against certain specific epitopes on CII are arthritogenic. Recently, the importance of cognate interactions between T-cells and B-cells to the induction of CIA was demonstrated by administration of monoclonal antibodies against a T-cell surface protein, gp39. Blocking the interaction of T-cell gp39, with its receptor/ligand on the surface of B-cells (CD40), completely blocked induction of CIA in mice. A concomitant reduction in the level of anti-CII IgG produced in anti-gp39-treated animals was observed, demonstrating the crucial importance of T-cell:B-cell interactions via gp39:CD-40 binding to the primary immune response to CII in vivo and therefore to the induction of CIA. Other features of CIA are important in elucidating the condition and this article will deal with some important issues.

Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue.

Vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), is a potent microvascular permeability enhancing cytokine and a selective mitogen for endothelial cells. It has been implicated in tumor angiogenesis and ascites fluid accumulation. Since development of the destructive synovial pannus in rheumatoid arthritis (RA) is associated with changes in vascular permeability (synovial fluid accumulation), synovial cell hyperplasia, and angiogenesis, we examined synovial fluids (SFs) and joint tissue for the expression and local accumulation of VPF/VEGF. VPF/VEGF was detected in all of 21 synovial fluids examined and when measured by an immunofluorimetric assay, ranged from 6.9 to 180.5 pM. These levels are biologically significant, since < 1 pM VPF/VEGF can elicit responses from its target cells, endothelial cells. Levels of VPF/VEGF were highest in rheumatoid arthritis fluids (n = 10), with a mean value (+/- SEM) of 59.1 +/- 18.0 pM, vs. 21.4 +/- 2.3 pM for 11 SFs from patients with other forms of arthritis (p = 0.042). In situ hybridization studies that were performed on joint tissues from patients with active RA revealed that synovial lining macrophages strongly expressed VPF/VEGF mRNA, and that microvascular endothelial cells of nearby blood vessels strongly expressed mRNA for the VPF/VEGF receptors, flt-1 and KDR. Immunohistochemistry performed on inflamed rheumatoid synovial tissue revealed that the VPF/VEGF peptide was localized to macrophages within inflamed synovium, as well as to microvascular endothelium, its putative target in the tissue. Together, these findings indicate that VPF/VEGF may have an important role in the pathogenesis of RA.

Annexin-1 localization in human skin: possible association with cytoskeletal elements in keratinocytes of the stratum spinosum.

Annexin-1 (also called lipocortin-1 or p35), a putative substrate of the epidermal growth factor/receptor kinase, protein kinase C, and transglutaminase, was immunolocalized in embryonic, neonatal, adult, and diseased human epidermis. In embryonic skin intense annexin-1 immunoreactivity was found in the periderm at 54 d estimated gestational age (EGA). Later (EGA = 91-143 d), annexin-1 immunoreactivity was restricted to basal keratinocytes. In neonatal skin, basal cells were often more heavily stained than were suprabasal keratinocytes, which were also stained. Only basal keratinocytes stained in adult plantar skin, but in thin skin annexin-1 was present in the basal, suprabasal, and sometimes even in the granular layers of the epidermis. Often, annexin-1 appeared concentrated around the perimeter of cells, especially tonofilament/desmosome-rich keratinocytes of the spinous-cell layer. At high magnification, annexin-1 appeared associated with distinct structures and was very granular in appearance in the intensely stained ductal keratinocytes of eccrine sweat glands, cells that are very highly enriched in keratin tonofilaments. This striking distribution in certain keratinocytes enriched in tonofilaments suggests a role for annexin-1 in cytoskeletal functions.

Critical role of peripheral blood phagocytes and the involvement of complement in tumour necrosis factor enhancement of passive collagen-arthritis.

Studies have implicated tumour necrosis factor-alpha (TNF-alpha) in type-II collagen (CII)-induced arthritis (CIA), a well established animal model of human rheumatoid arthritis. Precisely how TNF is involved in CIA is not yet clear. In this study the effects of TNF on CIA were examined, independent of its potential effects on the immune response, by performing peri-articular injection of TNF in combination with passive immunization of rats. A sub-arthritic dose (5 mg) of affinity-purified anti-CII IgG, which alone was insufficient to induce spontaneous clinical arthritis, was used throughout the study. Obvious clinical arthritis that persisted for several days was rapidly induced by injections of 100 ng TNF into hindpaws of rats that were passively immunized shortly before the TNF injection. Injections of TNF in non-immunized control rats did not induce clinical arthritis, nor did buffer-only injections in passively immunized controls. The clinical arthritic response was a local phenomenon, limited only to the TNF-injected hindpaws. No swelling was observed in the opposite, buffer-injected hindpaws, indicating the effects of TNF were not systemic. Depletion of peripheral blood phagocytes with anti-rat neutrophil antiserum before passive immunization completely abolished the ability of TNF to induce clinical arthritis, identifying phagocytic cells as the essential target cells in evoking this arthritic response. A role for complement activation was also demonstrated in this model through the use of a soluble recombinant version of CD35, the cell surface complement receptor type-1 (sCR1, BRL55730), which significantly reduced TNF-induced arthritis in phagocyte-replete rats.

Prevention of collagen-induced arthritis with an antibody to gp39, the ligand for CD40.

The ligand for the CD40 antigen is a 39-kilodalton protein, gp39, expressed on the surface of activated CD4+ T cells and is essential for thymus-dependent humoral immunity. The role of gp39-CD40 interactions in autoimmune disease was investigated in vivo with the use of an antibody that blocks their interactions (anti-gp39). Arthritis induced in mice by immunization with type II collagen was inhibited by anti-gp39. Anti-gp39 blocked the development of joint inflammation, serum antibody titers to collagen, the infiltration of inflammatory cells into the subsynovial tissue, and the erosion of cartilage and bone. Thus, interference with gp39-CD40 interactions may have therapeutic potential in the treatment of autoimmune disease.

Effect of propranolol in head tremor: quantitative study following single-dose and sustained drug administration.

The effect of the beta-adrenoceptor antagonist propranolol has been investigated in nine patients suffering from isolated (six patients) or prominent (three patients) essential tremor of the head. In a double-blind, placebo-controlled study the tremorolytic efficacy of propranolol has been assessed by a quantitative accelerometric method after a single oral dose (120 mg) and following 2 weeks of sustained treatment with two different dosage regimens of the drug (120 and 240 mg daily). As compared with placebo, a significant reduction in tremor magnitude was found following a single oral dose but not on sustained administration of the beta-blocker at either dosage. The results suggest that the efficacy of sustained propranolol on isolated or prominent essential head tremor is less predictable and satisfactory than expected on the basis of the single-dose response, as compared with hand tremor.

Acceleration of onset of collagen-induced arthritis by intra-articular injection of tumour necrosis factor or transforming growth factor-beta.

We examined whether tumour necrosis factor (TNF) or transforming growth factor-beta 1 (TGF-beta 1) could alter the course of collagen-induced arthritis (CIA). Injection of 100 ng TNF or 500 ng TGF-beta 1 into ankle joints of normal rats induced a very limited inflammatory response, observable only upon histological analysis. However, when injected into ankle joints of rats 9 days after immunization with bovine type II collagen (CII), identical doses of TNF or TGF-beta 1 induced a sustained, clinically obvious inflammation and oedema that began within 8 h on average, as compared to 90 h in CII-immunized control rats given no injections or intra-articular injections of buffer. The incidence of arthritis at 2 weeks post-immunization was 100% for TNF-injected hindpaws, compared with 55% for the control groups, a statistically significant difference. In rats passively immunized with a subarthritic dose of affinity purified antibody to rat-CII, intra-articular injection of 100 ng TNF or 500 ng of TGF-beta 1 also induced intense, though transient arthritis. The rapid proinflammatory effects in CIA described in this study and the synergy demonstrated between anti-CII IgG and either cytokine, suggest that these cytokines can participate locally in the pathogenesis of arthritis.

Determination of cimetidine and related impurities in pharmaceutical formulations by high-performance liquid chromatography.

The analytical characteristics of cimetidine tablets were studied. A high-performance liquid chromatographic method was developed in order to assay cimetidine and its related impurities simultaneously. A reversed-phase system and diode-array detector were used.

Transforming growth factor beta 1 (TGF-beta 1) induced neutrophil recruitment to synovial tissues: implications for TGF-beta-driven synovial inflammation and hyperplasia.

We have studied the consequences of introducing human recombinant transforming growth factor beta 1 (hrTGF-beta 1) into synovial tissue of the rat, to begin to better understand the significance of the fact that biologically active TGF-beta is found in human arthritic synovial effusions. Within 4-6 h after the intra-articular injection of 1 microgram of hrTGF-beta 1 into rat knee joints, extensive recruitment of polymorphonuclear leukocytes (PMNs) was observed. Cytochemistry and high resolution histological techniques were used to quantitate the influx of PMNs, which peaked 6 h post-injection. In a Boyden chamber assay, hrTGF-beta 1 at 1-10 fg/ml elicited a chemotactic response from PMNs greater in magnitude than that evoked by FMLP, establishing that TGF-beta 1 is an effective chemotactic agent for PMNs in vitro as well as in vivo. That PMNs may represent an important source of TGF-beta in inflammatory infiltrates was strongly suggested by a demonstration that stored TGF-beta 1 was secreted during phorbol myristate acetate-stimulated degranulation in vitro. Acid/ethanol extracts of human PMNs assayed by ELISA contained an average of 355 ng of TGF/beta 1 per 10(9) cells potentially available for secretion during degranulation of PMNs. [3H]Thymidine incorporation in vivo and autoradiography of tissue sections revealed that widespread cell proliferation was triggered by TGF-beta 1 injection. Synovial lining cells and cells located deep within the subsynovial connective tissue were identified as sources of at least some of the new cells that contribute to TGF-beta 1-induced hyperplasia. Our results demonstrate that TGF-beta is capable of exerting pathogenic effects on synovial tissue and that PMNs may represent a significant source of the TGF-beta present in synovial effusions.

Quantitative comparison of barbiturates in essential hand and head tremor.

The tremorolytic effects of primidone and phenobarbital in essential tremor of hands and head were compared in a double-blind, placebo-controlled trial. Quantitative measurements of tremor were obtained in 15 patients by means of an accelerometric method. Only primidone proved to be superior to placebo in reducing hand tremor, suggesting that its tremorolytic effectiveness is largely dependent on the parent drug rather than its metabolite phenobarbital. Head tremor tended to improve only in three out of six patients with both primidone and phenobarbital, but, likely due to the small number of affected patients, the effect failed to reach statistical significance.

Synthesis of transforming growth factor-beta 1 by megakaryocytes and its localization to megakaryocyte and platelet alpha-granules.

We have directly demonstrated that megakaryocytes are a major site of synthesis and storage of transforming growth factor-beta 1 (TGF/beta 1) by combined immunohistochemical, immunocytochemical, and in situ hybridization methods. The presence of TGF/beta 1 messenger RNA (mRNA) in mature megakaryocytes in adult rat spleen and bone marrow (BM) was established by in situ hybridization. Localization of TGF/beta 1 protein to intact alpha-granules of megakaryocytes, its putative storage site, was accomplished in glycol-methacrylate embedded porcine BM with an immunoperoxidase technique and light microscopy. The TGF/beta 1 was sequestered in intracytoplasmic granules in a pattern virtually identical to that of another alpha-granule marker protein, fibrinogen. This observation strongly suggests packaging of TGF/beta 1 into this organelle within megakaryocytes. That TGF/beta 1 mRNA was localized to megakaryocytes suggests that the TGF/beta 1 found in the alpha-granules in platelets originates with megakaryocyte synthesis. The alpha-granule localization of TGF/beta 1, as well as fibrinogen, was also demonstrated in isolated platelets at the ultrastructural level by electronmicroscopy (EM) and postembedding colloidal-gold immunocytochemistry, thus directly demonstrating that alpha-granules are the final storage site for TGF/beta 1 in mature platelets.

Clinical and computer-based assessment of long-term therapeutic efficacy of propranolol in essential tremor.

Despite a large number of studies demonstrating the effectiveness of propranolol in relieving essential tremor (ET) the long-term therapeutic outcome of these patients remains poorly defined. The results of a one-year follow-up study in 18 patients with mild to severe ET performed by using clinical and computer-based methods of assessment indicate that the initial therapeutic benefit of propranolol is apparently retained. However, following 3-6 months of sustained treatment a proportion of patients required an increase in daily dosage of propranolol in order to maintain adequate symptomatic control of tremor, indicating a relative decrease in tremorolytic efficacy of the drug possibly due to long-term tolerance.