Variations of lymphocyte sub-populations in vulvar condylomata during therapy with beta-interferon.

Several experiences induced us to consider genital HPV infection as an expression of a local immunodeficiency. The aim of our study was to research the effect of immunotherapy on the lymphocyte subpopulations and Langerhans cells in vulvar condyloma. Twenty women with persistent vulvar condylomata, treated with 2,000,000 IU/die of beta-interferon for 15 days, were submitted to vulvar biopsy before and 2-5 months after medical treatment. The frozen sections obtained were assayed with the following monoclonal antibodies: OKT 4 (T helper lymphocytes), OKT 8 (T suppressor lymphocytes), OKB 7 (B lymphocytes) and S-100 protein (Langerhans cells). Using a morphometric evaluation, the average number of both intraepithelial and stromal lymphocyte subsets and of the intraepithelial Langerhans cells was assessed. In all the biopsies preceeding the medical treatment we found a low number of T helper lymphocytes both in the epithelium and stroma, with inversion of T4/T8 lymphocyte ratio and rare presence of Langerhans cells. In patients with a good therapeutic response (50-100% of condyloma reduction) we observed an increase in intraepithelial T4 lymphocytes and a decrease in both intraepithelial and stromal T8 lymphocytes. In cases with persistent disease after therapy, the histological pattern was similar to that observed in the first biopsy, with the exception of a significant increase in the average number of Langerhans cells. Our data correlate the clinical response to the immunotherapy with the histology of lymphocyte subsets in the vulvar condylomata. The increase in Langerhans cells observed in patients with negative response may be interpreted with a probable inability of these cells to promote the immune reaction.     

Cytokine production, activation marker, and skin homing receptor in children with atopic dermatitis and bronchial asthma

T cells are known to develop a critical role in the pathogenesis of atopic dermatitis (AD) and bronchial asthma. T cells involved in AD express the skin homing receptor CLA, but no lung homing receptor has been identified in bronchial asthma. We compared different cell markers and the cytokine production in T cells from children with AD or bronchial asthma. We studied the involvement of CLA+ and CLA- T-cell subpopulations in these diseases. We studied 20 children with acute AD lesions, 15 with mild persistent asthma, and 15 non-atopic controls. All patients were sensitized to house dust mite (DP) and evaluated during the acute phase. Total and specific IgE were measured by immunoassay and the expression of different cell markers and the cytokine production was analyzed by flow cytometry in peripheral blood mononuclear cells. Total IgE was significantly higher in AD children and IgE to DP in the asthmatic children. There was a significant increase in CD25+ CD4+ cells in asthmatic children and in HLA-DR+ CD4+ and HLA-DR+ CD8+ cells in AD. In the CD4+ subsets, there was an increase in IL-13, IL-5 and TNF-alpha in AD compared to controls, a decrease in IFN-gamma in asthmatic children compared to controls, and an increase in IL-13, IL5, IL2, TNF-alpha, and IFN-gamma in the AD compared to asthmatic children. Changes in cytokine production were mainly detected in CLA+ cells in AD and in CLA- cells in asthma. Differences exist in total and specific IgE, activation markers, and cytokine patterns between AD children and children with asthma, with the former expressing a Th2 pattern whereas in asthmatic children we only detected a decrease in IFN-gamma. Moreover, the subpopulations (CLA+ vs. CLA-) expressing these changes were different, indicating that the underlying mechanisms in the two diseases are not exactly the same.     

Measurement of Pressure-Time Product during Spontaneous Assisted Breathing by Rapid Interrupter Technique

Background: Measuring the work of breathing of patients undergoing spontaneous assisted ventilation can be useful to monitor and titrate ventilatory support. The aim of this study was to obtain measurements of the pressure generated by the respiratory muscles (PMUSC) and the derived pressure-time product (PTP; a good indicator of the metabolic work of breathing), performing the rapid interrupter technique with a commercial ventilator.

Methods: A Draeger Evita 4 ventilator (Draeger Medical, Lubeck, Germany) was controlled by a personal computer to rapidly interrupt the airway flow at different times and volumes of the respiratory cycle during pressure-support ventilation. From the airway pressure tracing after the occlusion, the authors estimated the alveolar pressure and PMUSC; the integration of PMUSC values over the inspiratory time yields the measurement of PTP. Esophageal pressure measurements were used as a reference. After a bench study of the valves' performance, the authors performed 11 measurement sequences in eight patients.

Results: The closure times for the inspiratory and expiratory valves were 74 +/- 10 and 61 +/- 13 ms, respectively. The interrupter technique provided a reliable estimate of PMUSC (PMUSC, occl = 1.00 [middle dot] PMUSC, pes + 0.19; r = 0.88; 95% confidence interval for agreement, +5.49/-5.32 cm H2O). PTPoccl tightly correlated with PTPpes (PTPoccl = 0.95 [middle dot] PTPpes + 0.13; r = 0.96; 95% confidence interval, 1.94/-1.61 cm H2O [middle dot] s).     

Persistent dizziness after surgical treatment of vertigo: an exploratory study of prognostic factors.

OBJECTIVE: Persistent vertigo and imbalance can occur after surgery for vertigo regardless of surgical approach. This study explored for factors affecting outcome of vertigo surgery. STUDY DESIGN: Patient survey and chart review. SETTING: Tertiary referral neurotologic private practice. PATIENTS/INTERVENTION: Of 111 patients (57.7% female; mean age, 52.3 yr), 59 underwent vestibular nerve section (middle fossa, retrolabyrinthine, and translabyrinthine), 25 underwent transmastoid labyrinthectomy, and 27 underwent endolymphatic sac shunt. Eighty-three percent had Ménière's disease. Mean follow-up was 4.3 years. MAIN OUTCOME MEASURES: Primary outcomes included American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) vertigo score and class, number of spells per month, current and change in AAO-HNS disability rating, vertigo and imbalance severity ratings, and frequency of imbalance. RESULTS: Three preoperative factors were consistently related to outcome: AAO-HNS disability rating, imbalance frequency rating, and duration of first symptom ([rho] = 0.19-0.51; all p's < 0.05). Greater disability and more frequent imbalance related to poorer outcome, but longer duration of disease related to better outcome. Presurgery vertigo characteristics were generally not related to outcome. Ménière's patients were more likely to have improvement in imbalance, as were those with no other significant disease and no allergy. The presence of tinnitus in the contralateral ear was associated with poorer outcomes, including a lower rate of results of Classes A and B (p = 0.023). Vertigo as a first symptom and the presence of eye disease also showed relationships to poorer outcome. CONCLUSION: Those rating themselves as more disabled before surgery are less likely to achieve the best outcomes, whereas frequency and severity of preoperative vertigo are not predictive. Several possible prognostic factors were identified that warrant future prospective study.     

El cultivo celular en la investigación básica del cáncer de mama

Resumen La técnica del cultivo celular es la que ha permitido conocer el comportamientoin vitro de las células cancerosas. En esta revisión pretendemos introducir las peculiaridades básicas del cultivo celular, referido especialmente a líneas cancerosas mamarias, relacionar el origen de las líneas celulares más utilizadas en la investigación de este cáncer, mencionar las técnicas de laboratorio que pueden aplicarse sobre estos cultivos y ejemplificar la utilidad de las mismas, tomando como modelo diversos trabajos que estudian los efectos del factor de crecimiento epidérmico sobre líneas celulares hormonoindependientes de cáncer de mama.      

Transmitter Release Associated with Long-term Synaptic Depression in Rat Corticostriatal Slices

Using a corticostriatal slice preparation, we have recently shown that tetanic stimulation of the corticostriatal pathway produces long-term depression (LTD) of striatal excitatory synaptic transmission. In the present study we have analysed the relationship between LTD and the striatal release of different endogenous transmitters. Samples of perfusate were collected via a small cannula placed just above the surface of the striatal slice close to the recording electrode, and were analysed by HPLC. The high-frequency stimulation (100 Hz, three trains, 3 s duration, 20 s intervals) used to induce LTD caused a significant but transient increase in the release of both excitatory (aspartate and glutamate) and inhibitory (glycine and GABA) amino acid transmitters. Tetanic stimulation also produced a significant, but transient increase in the release of endogenous dopamine. We conclude that the tetanic stimulation of the corticostriatal pathway is able to induce a large but transient release of excitatory amino acids and of dopamine, whose participation in the induction of striatal LTD has been demonstrated previously. Moreover, the maintenance of this form of synaptic plasticity does not seem to require a sustained change in transmitter release.     

Suppression of B cell differentiation by ligation of membrane-bound IgM

Using B cells from the transgenic mouse line B6-Sp6 and control littermates, stimulated by lipopolysaccharide (LPS) under novel culture conditions that provide for the response of all B cells, we show here that specific ligation of the surface IgM molecules always results in inhibition of terminal differentiation and immunoglobulin secretion by activated cells, regardless of the ligand. Thus, monoclonal antibodies to (a) the CH region of Ig (anti-μ. and anti-allotype), (b) the Cx region, (c) the V region (anti-idiotype) of surface IgM, as well as (d) multivalent antigen (2,4,6-trinitrophenyl-bovine serum albumin), all show similar effects and dose-response curves. IgD-negative transgenic B cells are equally sensitive to IgM ligation-dependent inhibition, as control (IgD-positive) B cells. The allotype specificity of this inhibition, assessed by using anti-u, allotype reagents to inhibit and assay the responses, suggests that B cells expressing transgenic or endogenous IgM in transgenic B6-Sp6 mice are largely independent populations. These observations establish that anti-IgM antibodies in conjunction with appropriate LPS stimulation, provide a universal model system for functional characterization of B cell responses.