Early ultrastructural changes in RU-486-exposed decidua

An antiprogesterone (RU-486) was administered to women undergoing voluntary interruption of pregnancy. Five patients received 100 mg 12 h before surgical interruption, 5 others received 100 mg twice, 24 and 12 h before interruption, respectively, and another 5 received no drug at all and served as controls. Placentas and deciduae were examined morphologically with the light microscope and by electron microscopy. No specific lesions were detected in placental tissue. With conventional histology, the deciduae showed various degrees of interstitial edema and necrosis, changes which did not enable a distinction between treated cases and controls, although stromal disintegration tended to be more marked in RU-486-treated patients. At the ultrastructural level, the endothelium of decidual capillaries showed striking hyperplasia of the endoplasmic reticulum. Morphometric evaluation showed a statistically significant difference between RU-486-treated patients (2 X 100 mg) and controls. A possible link between these morphological changes and the induction of prostaglandin synthesis by the antiprogesterone is suggested. However, the full significance of the observed lesions remains uncertain and does not allow definite conclusions concerning the abortifacient effect of RU-486.     

Apoptosis protease activator protein-1 expression is dispensable for response of human melanoma cells to distinct proapoptotic agents

Loss of expression of the apoptosis protease activator protein-1 (APAF-1) in human melanoma is thought to promote resistance to programmed cell death by preventing caspase-9 activation. However, the role of the APAF-1-dependent pathway in apoptosis activated by cellular stress and/or DNA damage has been recently questioned. We investigated APAF-1 expression in a large panel of human melanomas and assessed cellular response to several proapoptotic agents in tumors expressing or lacking APAF-1 protein. In two melanomas with wild-type p53 but with differential expression of APAF-1, treatment with camptothecin, celecoxib, or an nitric oxide synthase inhibitor (1400W) significantly modulated expression of 36 of 96 genes in an apoptosis-specific cDNA macroarray, but APAF-1 mRNA levels were not induced (in APAF-1(-) cells) nor up-regulated (in APAF-1(+) cells), a finding confirmed at the protein level. Treatment with cisplatin, camptothecin, etoposide, betulinic acid, celecoxib, 1400W, and staurosporine promoted enzymatic activity not only of caspases -2, -8, and -3 but also of caspase-9 in both APAF-1(+) and APAF-1(-) tumor cells. Moreover, drug-induced caspase-9 enzymatic activity could be not only partially but significantly reduced by caspase-2, -3, and -8 -specific inhibitors in both APAF-1(+) and APAF-1(-) tumor cells. In response to 1 to 100 micromol/L of cisplatin, camptothecin, or celecoxib, APAF-1(+) melanomas (n = 12) did not show significantly increased levels of apoptosis compared with APAF-1(-) tumors (n = 7), with the exception of enhanced apoptosis in response to a very high dose (100 micromol/L) of etoposide. These results suggest that the response of human melanoma cells to different proapoptotic agents may be independent of their APAF-1 phenotype.     

Long-term use of oral contraceptive therapy in women with the prothrombin 20210 G-A polymorphism without thrombotic complications: a study of 13 women (12 heterozygotes and 1 homozygote)

Thirteen female patients with the prothrombin 20210 G-A abnormality (twelve heterozygotes and one homozygote) were selected out of 551 patients admitted to our Department of Medicine or to our Outpatient Hemostasis Units between January 1999 and October 2000. The selection was based on the fact that all patients had taken or were still taking oral contraceptives (OC) for a period of 3 years or longer than 3 years. None of these patents as gathered from history, physical examination, private physician records and our records has shown any DVT during or immediately after OC intake. Physical and compression ultrasonography examinations at the time of study were all negative. The average length of oral contraceptives therapy (OCT) was 10 years (range 3-23). The average age of patients at the time of oral contraception was 30 years. The 13 women had also 17 pregnancies without any venous thrombosis. The observations casts several doubt about the prothrombotic effect of this polymorphism. Since DVT has been shown to occur occasionally even in normal women, it is likely that the same may occur in women with this polymorphism regardless of the existence or not of any pathogenetic relationship between the two phenomena. Occasional reports suggesting a link between this polymorphism and oral contraception-related venous thrombosis should be carefully evaluated in order to avoid premature and incorrect conclusions.     

Muscle transplant in the rabbit's Achilles tendon

Achilles tendinopathy (AT) is a degenerative disorder resulting from functional overload, especially during running and jumping, with some inflammatory features at the insertions, bursae, and paratenon. The Achilles tendon is poorly vascularized, especially in the middle third, and the consequent slow metabolic rate allows it to work at very low oxygen tensions but prevents on the other hand a rapid healing. PURPOSE: To create an animal model to study a novel surgical technique employed in AT: transplanting some fibers of the soleus muscle into the tendon in order to improve its vascularization and healing and to study the histological appearance of the soleus graft incorporated in the tendon. METHODS: We operated on 10 white New Zealand rabbits (eight rabbits underwent the procedure, two rabbits the sham operation with incision of the tendon without graft). Two animals were euthanized at 1 wk, 1, 2, and 3 months. RESULTS: Histology showed that after 3 months the muscle fibers were still viable within the tendons, interspersed within connective tissue fibers. Tendon and muscle tissues were intimately fused. CONCLUSIONS: The persistence of the soleus muscle pedicle graft within the Achilles tendon tissue is an index of sound blood supply. This surgical model is suitable for application in further studies on tendon healing.     

Perceived challenges and attitudes to regimen and product selection from Italian haemophilia treaters: the 2013 AICE survey

Despite great advances in haemophilia care in the last 20 years, a number of questions on haemophilia therapy remain unanswered. These debated issues primarily involve the choice of the product type (plasma‐derived vs. recombinant) for patients with different characteristics: specifically, if they were infected by blood‐borne virus infections, and if they bear high or low risk of inhibitor development. In addition, the most appropriate treatment regimen in non‐inhibitor and inhibitor patients compel physicians operating at the haemophilia treatment centres (HTCs) to take important therapeutic decisions, which are often based on their personal clinical experience rather than on evidence‐based recommendations from published literature data. To know the opinion on the most controversial aspects in haemophilia care of Italian expert physicians, who are responsible for common clinical practice and therapeutic decisions, we have conducted a survey among the Directors of HTCs affiliated to the Italian Association of Haemophilia Centres (AICE). A questionnaire, consisting of 19 questions covering the most important topics related to haemophilia treatment, was sent to the Directors of all 52 Italian HTCs. Forty Directors out of 52 (76.9%) responded, accounting for the large majority of HTCs affiliated to the AICE throughout Italy. The results of this survey provide for the first time a picture of the attitudes towards clotting factor concentrate use and product selection of clinicians working at Italian HTCs.     

TNF-Based Isolated Limb Perfusion Followed by Consolidation Biotherapy with Systemic Low-dose Interferon Alpha 2b in Patients with In-transit Melanoma Metastases: A Pilot Trial

BACKGROUND: Tumor necrosis factor (TNF)-based isolated limb perfusion (ILP) yields high tumor response rates in patients with in-transit melanoma metastases. However, most patients will ultimately experience disease recurrence. The aim of this pilot study was to test the hypothesis that systemic low-dose interferon alpha-2b (LDI) might consolidate the therapeutic effect of ILP. METHODS: A total of 12 patients with in-transit melanoma metastases not amenable to surgical excision were given LDI subcutaneously (3 million IU/day, 7 days/week for 12 months) after TNF-based ILP (TNF 1 mg + melphalan (L-PAM) 10 mg/L) (group A). The clinical outcome of these patients was historically compared with that of 19 patients with similar anthropometric and disease characteristics who underwent TNF-based ILP alone (group B). RESULTS: In group A, LDI was well tolerated, only grade 2 systemic toxicity being recorded in 50% of patients. The progression-free survival analysis showed a statistically significant advantage for group A patients as compared with group B (median time to progression: 26 and 17 months, respectively; log-rank test P-value: 0.037). This survival benefit was confirmed at multivariate analysis, where treatment was the only prognostic factor retained by the prediction model. The analysis of the risk of disease progression over time suggested that this survival benefit appears to vanish after LDI discontinuation, which further strengthens the hypothesis that LDI might consolidate the therapeutic effect of TNF-based ILP. CONCLUSIONS: These preliminary findings support the conduction of larger trials to formally assess the ability of LDI to improve the clinical outcome of melanoma patients with in-transit metastases undergoing TNF-based ILP.     

Lateral ankle instability in high-demand athletes: reconstruction with fibular periosteal flap

Purpose

Fibular periosteal flaps have been used to address chronic lateral ankle instability, but there are no studies in the literature reporting functional outcomes after this particular procedure in high-demand athletes. We postulated that for chronic instability, nonanatomical reconstruction of the lateral ankle ligament with a fibular periosteal flap will return high-demand athletes to their previous levels of activity.

Methods

Forty patients who had grade III ankle sprain and experienced no success after a course of supervised conservative management lasting at least six months and who had a preinjury Tegner score of ≥6 underwent a lateral compartment reconstruction with a fibular periosteal flap. Each patient was given the Tegner and Karlsson questionnaire and was evaluated by the Zwipp method, Foot and Ankle Outcome Score (FAOS) and the American Orthopaedic Foot and Ankle Society (AOFAS) score at the six-month, one, two and three-year time points. Range of motion (ROM) of the affected ankle was assessed, and stress X-rays were performed. Mean patient age was 24.5 (range17–30) years, and no patient was lost to follow-up.

Results

Mean follow-up was 36 (minimum 18) months, mean Tegner scores at the one, two and three-year time points were 8.8, 8.9 and 8.9, respectively, and mean Karlsson scores were 93 ± 5.2, 95 ± 3.1 and 94.9, respectively. AOFAS and FAOS scores improved from a mean of 69.4 and 71.4, respectively, in the preoperative group to a mean of 97.2 and 94.4, respectively, at the last follow-up. The ROM was equal to the contralateral ankle in all but two patients at the two-year follow-up. No major complications were found.

Conclusion

Nonanatomical ligament reconstruction with a fibular periosteal flap for chronic lateral ankle instability was effective in returning high-demand athletes to their preinjury functional levels.