Voluntary contraction of the tensor tympani muscle and its audiometric effects.

BACKGROUND: The tensor tympani muscle is the largest muscle within the middle ear. Its voluntary contraction is a very unusual event. Only a few papers have documented its audiometric effects. OBJECTIVE: To report an unusual case of voluntary tensor tympani muscle contraction and describe its audiometric effects. CASE REPORT: A 27-year-old man, who presented complaining of voluntarily evoked bilateral tinnitus, was found to be able to voluntarily contract the tensor tympani muscle in both ears simultaneously. Audiograms were performed under conditions of rest and maximal contraction of the tensor tympani muscle. The most remarkable effects were conductive hearing loss at lower frequencies and an increase in middle-ear impedance. CONCLUSION: The importance of the tensor tympani muscle in middle-ear physiology remains unclear. It has been related to the attenuation of sounds produced during the mastication process. Voluntary control over the tensor tympani muscle is an extremely rare event. However, an understanding of the potential audiometric effects of its contraction could aid the diagnosis of hearing disorders.

Gore external valve support for superficial saphenous vein incompetence: a 10-year, follow-up registry.

AIM: This long-term (10-year) study evaluated the safety and efficacy of expanded polytetrafluoroethylene (ePTFE) external valve support (EVS) implants used for external valvuloplasty in the treatment of incompetence of the proximal long saphenous veins. METHODS: During a 10-year follow-up, patients with superficial venous disease and venous hypertension due to pure superficial vein incompetence underwent an external valvuloplasty using an EVS with a PTFE suture. Forty-nine patients were included in the EVS group and 47 in the control group. Patients with superficial venous disease and venous hypertension due to pure superficial venous incompetence were randomised into two treatment groups. The first group was treated with what was considered "conventional treatment" (ligation or stripping) and the second with external valvuloplasty with EVS. This report deals with controls treated with ligation as only 6 cases (not mentioned in this report) were treated with stripping. There were no significant differences in the two groups concerning age, sex, or type of venous insufficiency. The procedures focused on only one single limb per patient. RESULTS: 46.9% of limbs treated with EVS developed varices in comparison with 73% in the control group. New surgical procedures (localized ligation) were needed in 32.6% of the EVS patients vs. 55.3% in controls. Sclerotherapy was used in 42% of the EVS patients vs. 72.34% in controls. At 10 years the SFJ was incompetent (reflux) in 2 EVS patients (4%); one after 5 years and one after 7 years. There was no incompetence at the level of the ligated junction in controls. There were 62 incompetent venous sites (1.26 per limb) in the EVS group vs. 96 new incompetent venous sites (2.04 per limb) in controls. In controls 10.63% of the limbs developed minor discolorations and signs due to mild CVI; none was observed in the EVS group. In all ESV implants there was full restoration of competence at 1 year. CONCLUSION: EVS implants used to correct superficial venous incompetence at 10 years were well tolerated and produced good results on incompetence and on the evolution of varicose veins.

Sublingual immunotherapy with Dermatophagoides monomeric allergoid down-regulates allergen-specific immunoglobulin E and increases both interferon-gamma- and interleukin-10-production.

BACKGROUND: The clinical efficacy and safety of sublingual immunotherapy (SLIT) for aeroallergens has been demonstrated in several trials, whereas the immunological changes induced by this treatment, which may account for the clinical improvement, are still unclear. OBJECTIVE: To investigate the effects of a successful SLIT on the in vitro allergen-driven T cell response and cytokine secretion as well as on the serum levels of chemokines and of IgE, IgG1 and IgG4 antibodies (Abs). MATERIALS AND METHODS: Twenty-five Dermatophagoides pteronyssinus (Dp)-sensitive patients with perennial rhinitic and/or rhinitic and asthmatic symptoms were randomized into two groups (13 untreated (UT) and 12 SLIT-treated) for a 1 year and half study. The proliferative response of peripheral blood mononuclear cell (PBMC) to purified Der p1 allergen, their cytokines (IFN-gamma, IL-4, IL-10 and TGF-beta) production and serum levels of chemokines associated with T helper type 1 (Th1) (CXCL10) or T helper type 2 (Th2) (CCL22) responses and of Dp-specific IgE, IgG1 and IgG4 Abs were evaluated before and after 6 months of treatment. RESULTS: SLIT induced a significant reduction of symptom medication scores after 6, 12 and 18 months of treatment in comparison with UT patients. SLIT-treated patients showed a significant decrease in serum levels of DP-specific IgE Abs, whereas total IgE, and specific IgG1 and IgG4 Abs remained unchanged. The proliferative response of allergen-specific T cells to Der p1 in vitro after 6 months of treatment was reduced, while no effect was observed on T cell proliferation to recall antigen (streptokinase). Moreover, Der p1-driven IFN-gamma and IL-10 were significantly increased in culture supernatants of PBMC from 6 month-treated patients in comparison with those detected at the beginning of therapy. CONCLUSIONS: These data suggest that the allergen-driven enhancement of IL-10- and IFN-gamma-producing T cells precedes and associates with SLIT-induced down-regulation of specific IgE, thus providing a rationale to explain the clinical benefit of SLIT in allergic patients.

CXCR3 and alphaEbeta7 integrin identify a subset of CD8+ mature thymocytes that share phenotypic and functional properties with CD8+ gut intraepithelial lymphocytes.

BACKGROUND: We previously demonstrated the existence of two distinct subsets of T cell receptor (TCR)alphabeta+CD8alphabeta+ single positive (SP) cells in human postnatal thymus which express the chemokine receptor CCR7 or CXCR3 and migrate in vitro in response to their specific ligands. AIM: To investigate whether these two CD8+ thymocyte subsets had distinct peripheral colonisation. METHODS: TCRalphabeta+CD8+ SP cells were obtained from normal postnatal thymus, mesenteric lymph node (LNs), small bowel, and peripheral blood (PB) specimens. Cells were then evaluated for expression of surface molecules, cytolytic potential, telomere length, and profile of cytokine production. RESULTS: CD8+CCR7+CXCR3- thymocytes exhibited CD62L, in common with those which localise to LNs. In contrast, CD8+CCR7-CXCR3+ thymocytes lacked CD62L but exhibited CD103, similar to intraepithelial lymphocytes (IELs) present in the gut mucosa where the CXCR3 ligand, CXCL10, and the CD103 ligand, E-cadherin, are highly and consistently expressed. In addition, thymocytes and gut CD8+CXCR3+CD103+ cells showed comparable telomere length, which was higher than that of PB CXCR3+CD8+ T cells. However, both of these populations contained perforin and granzyme A, and displayed the ability to produce interferon gamma and interleukin 2. Of note, CXCR3 deficient, in comparison with wild-type C57Black/6, mice showed decreased proportions of CD3+CD8alphabeta+ and increased proportions of CD3+CD8alphaalpha+ lymphocytes at gut level. Moreover, adoptive transfer of CD3+CD8alphabeta+ thymocytes from wild-type into CXCR3 deficient mice resulted in a significant increase in CD3+CD8alphabeta+ T cells in the gut mucosa but not in other tissues. CONCLUSIONS: The results of this study demonstrate the existence of a previously unrecognised subset of TCRalphabeta+CD8alphabeta+ SP CXCR3+CD103+ thymocytes which share phenotypic and functional features with CD8+ IELs, thus suggesting the possibility of their direct colonisation of the gut mucosa.

Effects of blocking urokinase receptor signaling by antisense oligonucleotides in a mouse model of experimental prostate cancer bone metastases.

An important factor implicated in tumor cell predisposition for invasion and metastasis is the malignancy-related upregulation of urokinase plasminogen activator receptor (uPAR). uPAR signals by activating different tyrosine kinases in different cells. We examined the effects of inhibiting uPAR signaling by inhibition of uPAR expression with antisense oligonucleotides (aODNs) in PC3 human prostate cancer cells and evaluated aODN effect in a mouse model of prostate cancer bone metastasis. Following uPAR aODN treatment, PC3 cells exhibited a strong decrease in uPAR expression, evaluated by flow cytometry and by polymerase chain reaction, and of FAK/JNK/Jun phosphorylation. The synthesis of cyclins A, B, D1 and D3 was inhibited, as shown by Western blotting, flow cytometry and polymerase chain reaction, and PC3 cells accumulated in the G2 phase of the cell cycle. PC3 cells' adhesion was unaffected, while proliferation and invasion of Matrigel were impaired. A total of 60 mice were subjected to intracardiac injection of PC3 cells and were randomly assigned to three groups: aODN (treated with 0.5 mg intraperitoneum/mouse/day), dODN (treated with the same amounts of a degenerated ODN) and control (injected with a saline solution). At 28 days after heart injection, mice were subjected to a digital scan of total body radiography, which revealed 80% reduction in mice affected by bone metastasis. The use of uPAR aODNs produced a substantial prophylactic effect against prostate cancer bone metastasis, which has to be ascribed to downregulation of uPAR expression.

Clinical effects of a standardized soy extract in postmenopausal women: a pilot study.

OBJECTIVE: This double-blind, randomized study was aimed at evaluating comparatively, in postmenopausal women, the activity of a standardized soy extract (SOYSELECT) and placebo when given alone or in combination with conjugated equine estrogens (CEE) on early climacteric symptoms. Lipid profile, pituitary hormones, osteocalcin and endothelin levels, and vaginal and endometrial parameters were also evaluated. DESIGN: Participants in the control group were given placebo, and participants in the treated group were given 400 mg/day of a standardized soy extract, corresponding to 50 mg/daily of isoflavones. After 6 weeks of treatment, CEE was also then given to each participant at a dose of 0.625 mg/day for 4 weeks. At the end of this period, soy and placebo treatment were suspended, and, until the end of the study (week 12), participants were administered 10 mg/day of medroxyprogesterone acetate in association with CEE (0.625 mg/day). RESULTS: When compared with pretreatment data, on week 6 of the study, a significant (p < 0.01) reduction in the mean number of hot flushes per week was observed in participants who were receiving the standardized soy extract, whereas a more marked relief was observed in both soy and placebo groups during CEE administration. Concurrently, the severity of hot flushes, assessed by means of the Greene climacteric scale, was also reduced in the soy group participants (p < 0.001, by paired t-test). No soy-related changes were observed on vaginal cytology, endometrial thickness, uterine artery pulsatility index, or metabolic and hormonal parameters tested. Finally, CEE-related changes on genital tract, uterine vascular compartment, and pituitary hormones were not modified by soy treatment. CONCLUSIONS: SOYSELECT may be a safe and efficacious therapy for relief of hot flushes in women who refuse or have contraindications for hormone replacement therapy.

Diagnostic and therapeutic technique of cervical conization with "cold knife" using fibrin glue. Preliminary outcomes.

In recent years many Authors have proposed several techniques and surgical tools to perform conical or cylindrical excisions of the portio and cervical canal. For instance, we can perform conization using a traditional "cold knife" (scalpel), CO2 laser with focal bundle, radiothermic or fine needle electroconization (Loop Electrosurgical Excision Procedure-LEEP-; Large Loop Excision of Transition Zone-LLETZ-). Our goal has been to change traditional conization of the cervix with "cold knife" using Hegar dilatators to delineate the cone we have to remove and prevent lesions in the cervical canal; furthermore, using fibrin glue (Tissucol-R) to do a considerable haemostasis. The performance takes about five minutes under local anaesthesia and it has been possible to study the patients with a 24-month follow up. The results the Authors obtained have been low blood loss, diagnostic and histological accuracy, better colposcopic follow-up, any angle-shots or abnormality of the cervical canal and any physical-chemical modifications of the ovulatory cervical mucus. The advantages of traditional conization we modified are still valid; however, others procedures have a clinical and therapeutical significance but concerning histological and diagnostic investigations they could give a negative result.

[Autoimmune thrombocytopenia and pregnancy]. / Trombocitopenia autoimmune e gravidanza.

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder with its highest frequency in young women in the reproductive years. An antepartum diagnosis of maternal thrombocytopenia has become more common because platelet counts are now included with routine complete blood cell counts. Sometimes platelet autoantibodies facilitate increased platelet destruction by the reticuloendothelial system especially the spleen. These autoantibodies (IgG) can cross the placenta and place the fetus at risk for thrombocytopenia and, sometimes, serious bleeding problems such as intracranial hemorrhage can occur. The treatment is performed by corticosteroids (prednisone) or intravenous immune gammaglobulin. Four patients with thrombocytopenia during pregnancy underwent medical treatment (prednisone 1 mg/kg/die). The results were successful. In one case only we did not have a clinical response after corticosteroid therapy. There were no intracranial hemorrhages; however the risk for the patients and fetal or neonatal hemorrhage is much lower than thought. Corticosteroid treatment is the first choice, but sometimes it can give a clinical negative response.

Immunochemical CK-MB assay for myocardial infarction.

The diagnostic efficiency of an immunochemical assay for CK-MB (I-MB) was compared with that of an electrophoretic procedure for this isoenzyme (E-MB) in 215 consecutive patients in whom acute myocardial infarction (MI) was clinically suspected. All patients were investigated with a standard protocol consisting of serial assays of total creatine kinase (CK) and lactic dehydrogenase (LD) activities, CK-MB and LD1 isoenzymes, and electrocardiograms. Technetium pyrophosphate cardiac scans were obtained for eleven patients; autopsy was performed in six cases. The diagnosis of acute MI was established in 45 patients. The coefficients of variation for the intra-assay and interassay precision of I-MB assay ranged from 2.05%-7.2%. Concordance between the I-MB and E-MB results at the decision values for acute MI was observed in 203 of 215 patients (94.4%). At the cut-off point of 10 U/L, the I-MB assay was 95.5% sensitive and 95.3% specific for acute MI; the corresponding rates for the E-MB test were 93.3% and 94.7% respectively. The test efficiency rate for I-MB assay was 95.3% and that of E-MB procedure 94.4%. A complete time-based isoenzyme protocol for the diagnosis of acute myocardial infarction has several variables; the need for interpretation of individual profiles and for the preparation of a formal report is discussed.