Arthroscopic Latarjet procedure: analysis of the learning curve.

BACKGROUND: The arthroscopic Latarjet procedure is an innovative technique that aims to combine the optimal results of the original open approach with those of arthroscopic stabilization. METHODS: We evaluated the learning curve and the preliminary results of the first 30 patients (29 males, 1 female; mean age 32 years, range 21-52) subjected to an arthroscopic Latarjet procedure at a mean follow-up of 13 months (range 6-22). RESULTS: Operative time fell significantly from 132 to 99 min (p < 0.001, t test) in the last 15 patients compared with the first 15 without significant differences in terms of Rowe score, patient satisfaction, complications, or graft placement. There were 21 (70 %) excellent and 9 (30 %) good outcomes according to the Rowe score. All complications (10 %) correlated with age >40 years (p = 0.002, Fisher's exact test). CONCLUSIONS: The arthroscopic Latarjet procedure is a standardized, hence reproducible technique whose complexity makes it suitable only for surgeons with solid experience in arthroscopy and shoulder surgery.

Shoulder hemiarthroplasty for fractures of the proximal humerus.

Proximal humeral fractures were managed with primary hemiarthroplasty in 57 patients, 53 women (93%) and 4 men (7%) aged 51-87 years (mean 72.2). The mean follow-up period was 52 months (range 12-98), and the mean Constant score was 59.2 (range 38-76). Patients were very satisfied (n = 19); satisfied (n = 32) or dissatisfied with the outcome (n = 5). One patient required early revision surgery. Surgical treatment of three- and four-part fractures of the proximal humerus with hemiarthroplasty is a safe and effective approach, the outcome of which appears to be related to the quality of the anatomical reconstruction of the tuberosities.

Evaluating the use of multiple microswitches and responses for children with multiple disabilities.

BACKGROUND: The present study assessed the feasibility of (1) establishing multiple microswitches and responses (some of which had not been used before) with two children with multiple disabilities, and (2) maintaining such microswitches and responses in the children's daily contexts. METHODS: The microswitches were introduced individually and then combined. During the last part of treatment and the follow-up, each child had three microswitches. RESULTS: The data show that both children learned to use all three available microswitches. Moreover, they retained fairly high levels of responding with the microswitches in their daily contexts during follow-up periods of 4 and 6 months. CONCLUSIONS: The personal and practical implications of these findings are discussed.

Interaction between novel anticancer agents and radiation in non-small cell lung cancer cell lines.

Integration of chemotherapy and radiation is the standard practice in the management of locally advanced inoperable NSCLC. To assess the biological interaction between third generation chemotherapeutic agents and radiation in non-small cell lung cancer (NSCLC) in vitro, we tested a number of different drugs (paclitaxel, docetaxel, gemcitabine, topotecan, SN-38 and cisplatin) combined with radiation, in lung cancer cell lines. Cellular chemosensitivity was determined, using the semi-automated colorimetric MTT assay, after 48, 72 and 96 h of exposure to increasing drug concentrations, (0.001-100 microM) and radiation doses (100-400 cGy). Cell lines used were the adenocarcinoma (ADK), A-549, and the squamous-cell carcinoma (SCC), LX-1. Cells were pre-treated with anticancer agents at 24, 12 and 0 h before irradiation. Cytofluorimetric cell cycle analysis was performed. A significant S-phase block or a G(2)/M block was seen with gemcitabine and topotecan or paclitaxel pre-treatment, respectively. Apoptosis was seen only after paclitaxel exposure in the A-549 cell line. Despite a similar pattern of cell-kinetic changes induced by chemotherapy pre-treatment in all cell lines, the adenocarcinoma A-549 cell line was not radiosensitized by any of the anticancer agents tested, whereas synergism was observed in the LX-1 squamous carcinoma cell line, when exposed to gemcitabine, SN-38, topotecan and cisplatin. Paclitaxel, despite a favourable cell cycle effect, was not found to be synergistic with radiotherapy in our experimental model. In conclusion, the observed synergism appears to be dose- and timing-independent and seems to be related to the histological subtype being present in SCC only. Favourable perturbation of the cell cycle is evident with all the new agents tested in both cell types, but was not sufficient to produce synergism with radiation.

Stromal cell-derived factor-1alpha induces astrocyte proliferation through the activation of extracellular signal-regulated kinases 1/2 pathway.

Stromal cell-derived factor-1 (SDF-1), the ligand of the CXCR4 receptor, is a chemokine involved in chemotaxis and brain development that also acts as co-receptor for HIV-1 infection. We previously demonstrated that CXCR4 and SDF-1alpha are expressed in cultured type-I cortical rat astrocytes, cortical neurones and cerebellar granule cells. Here, we investigated the possible functions of CXCR4 expressed in rat type-I cortical astrocytes and demonstrated that SDF-1alpha stimulated the proliferation of these cells in vitro. The proliferative activity induced by SDF-1alpha in astrocytes was reduced by PD98059, indicating the involvement of extracellular signal-regulated kinases (ERK1/2) in the astrocyte proliferation induced by CXCR4 stimulation. This observation was further confirmed showing that SDF-1alpha treatment selectively activated ERK1/2, but not p38 or stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). Moreover, both astrocyte proliferation and ERK1/2 phosphorylation, induced by SDF-1alpha, were inhibited by pertussis toxin (PTX) and wortmannin treatment indicating the involvement of a PTX sensitive G-protein and of phosphatidyl inositol-3 kinase in the signalling of SDF-1alpha. In addition, Pyk2 activation represent an upstream components for the CXCR4 signalling to ERK1/2 in astrocytes. To our knowledge, this is the first report demonstrating a proliferative effect for SDF-1alpha in primary cultures of rat type-I astrocytes, and showing that the activation of ERK1/2 is responsible for this effect. These data suggest that CXCR4/SDF-1 should play an important role in physiological and pathological glial proliferation, such as brain development, reactive gliosis and brain tumour formation.

Pre-clinical evaluation of new antineoplastic agents in NSCLC cell lines: evidence of histological subtype-dependent cytotoxicity.

The antiproliferative effect of paclitaxel, docetaxel, gemcitabine, topotecan, SN-38 and cis-platin was studied on 5 non-small cell lung cancer (NSCLC) cell lines, 3 of which were adenocarcinoma (ADK) and 2 squamous cell carcinoma (SCC). Cellular chemosensitivity was determined using the MTT in vitro assay after 48, 72 and 96 h of exposure to drug in concentration ranging from 0.001 to 100 microM. A concentration-dependent cell growth inhibition was observed for paclitaxel, gemcitabine, topotecan, SN-38 and cis-platin in all cell lines tested. Docetaxel showed a concentration-independent cytotoxicity and was 104 times more potent than cis-platin (IC50 = 0. 001 vs. 10 microM). Paclitaxel, gemcitabine, topotecan and SN-38 were 102 times more potent than cis-platin, with median IC50 = 0.1 microM at 72 h. The level of drug-induced cell growth inhibition appeared to be correlated, for some of the six drugs tested, with the tumor histological subtype. In particular, topotecan and cis-platin were more active in squamous cell carcinoma than in adenocarcinoma cell lines (p=0.006 and 0.001 respectively at 0.1 microM concentration), while paclitaxel was more active in ADK than in SCC cell lines (p=0.004 at 0.01 microM concentration). Ca-Lu-6, a cell line that, contrary to most other lung cancer cell lines, is wild-type for most oncogenes/tumor suppressor genes, was by far the most sensitive cell line used (p=0.002, 0.003, 0.01 for paclitaxel, topotecan and cis-platin respectively, at 1 microM concentration), showing a >50% growth inhibition to new drugs at a concentration of 0.01 microM. In conclusion, all these new compounds tested were found to be more potent than cis-platin in affecting cellular proliferation of six NSCLC cell lines studied. We suggest that the specific histological subtype and molecular pattern of the cell line being treated could affect the antiproliferative effect of these drugs.

Responsiveness to hormone, growth factor and drug treatment of a human breast cancer cell line: comparison between early and late cultures.

Growth rate, morphology, and responsiveness to mitogenic stimuli and pharmacological treatments were evaluated in early and late cell passages derived from the same clone of the widely used MCF-7 human breast adenocarcinoma cell line. Our results indicate dissimilarities between early (E) and late (L) passages for some of the parameters analyzed. The cells that underwent many subcultivations grew faster than the others; both appeared homogeneous in size and shape. The E cells, subcultured for almost 1 yr, displayed higher sensitivity to the mitogenic action of both estradiol, according to the level of estrogen receptor, and insulin-like growth factor-I than did the L cells, kept in culture for more than 10 yr. Cell responsiveness to two drugs, a novel steroid antiestrogen and a polysulfonated distamycin A derivative, was more pronounced in the early cultures only at the longer time of exposure to the higher concentration of the estrogen antagonist. In addition, a drug-induced inhibition of insulin-like growth factor-I binding to its receptor was shown in both E and L cells, the latter being less sensitive than the former when exposed to the antiestrogen. Finally, MCF-7 E and L cells showed similar behavior when drug-induced apoptosis was tested.

Establishment and preliminary characterization of human malignant mesothelioma cell lines.

Malignant mesothelioma is an aggressive and rare tumor of the mesothelium which arises in serosal cavities and is strongly related to asbestos exposure. The incidence of this tumor is still increasing because of the widespread use of asbestos over the past years and the long latency of this malignancy. The paucity of well-characterized in vitro human models and the consequent shortage of experimental pharmacological studies on mesothelioma reduce the success of its clinical management. It is well known that established human cell lines represent a rapid and advantageous system for in vitro studies of several diseases, such as mesothelioma. Thus, the aim of our study was to establish and characterize a panel of selected human malignant mesothelioma cell lines in order to highlight the biology of this tumor and to test the effectiveness of new antiproliferative compounds. During the last year, we collected 10 pleural effusion samples from patients with diagnosed and pharmacologically untreated mesothelioma. Among these, we were able to isolate three continuously growing cell lines, identified as IST-Mes1, IST-Mes2 and IST-Mes3. Another previously established malignant mesothelioma cell line (MPP89) has also been included in this study. The cells in culture appeared morphologically heterogeneous: three of them (IST-Mes1, IST-Mes2, and MPP89) were spindle-shaped, and upon reaching confluence, they assumed the characteristic cobblestone-like pattern, whereas IST-Mes3 showed mixed sizes and shapes. Cell growth studies revealed that all cell lines reach exponential growth phase within 4-7 days after plating with a doubling time ranging from 37-87 hours. Finally, insulin-like growth factor-I did not stimulate cellular proliferation of both the IST-Mes1 and IST-Mes2 cell lines.

Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)-retinamide in human breast cancer cell lines.

The potent mitogenic activity of insulin-like growth factor I (IGF-I) on breast epithelium is inhibited by retinoic acid in oestrogen receptor-positive (ER+) breast cancer cell lines. We studied and compared the effects of N-(4-hydroxyphenyl)-retinamide (4-HPR) in terms of growth inhibition and modulation of the IGF-I system in ER+ (MCF-7) and oestrogen receptor-negative (ER-) (MDA-MB231) breast cancer cell lines. Treatment with 1-10 microM 4-HPR for up to 96 h induced a dose- and time-dependent inhibition of proliferation in both breast cancer cell lines. Induction of apoptosis was much more evident in MCF-7 than in MDA-MB231 cells (30-40% compared with 0-5% respectively at 5 microM for 48 h). Exogenous human recombinant IGF-I (hr-IGF-I)-stimulated cell proliferation was abolished by 1 microM 4-HPR in MCF-7 cells. Immunoreactive IGF-I-like protein concentration in conditioned medium was reduced by 38% in MCF-7 and by 90% in MDA-MB231 cell lines following treatment for 48 h with 5 microM 4-HPR. Western ligand blot analysis showed a reduction of IGF-binding protein 4 (BP4) and BP5 by 67% and 87%, respectively, in MCF-7, whereas IGF-BP4 and -BP1 were reduced by approximately 20% in MDA-MB231 cells. Exposure to 5 microM 4-HPR for 48 h inhibited [125I]IGF-I binding and Scatchard analysis revealed a decrease of more than 50% in maximum binding capacity (Bmax) and a reduced receptor number/cell in both cancer cell lines. Steady-state type I IGF-receptor mRNA levels were reduced by approximately 30% in both tumour cell lines. We conclude that 4-HPR induces a significant down-regulation of the IGF-I system in both ER+ (MCF-7) and ER- (MDA-MB231) breast cancer cell lines. These findings suggest that, in our model, interference with the ER signalling pathway is not the only mechanism of breast cancer growth inhibition by 4-HPR.

Principles of contact lens tonometry.

We constructed a contact lens with an integrated pressure-sensing device. It is housed in a container with three force-sensing elements, each 120 degrees apart, enabling measurement of the appositional force, i.e., the force with which the instrument is held against the eye. In part 1 of the study, the lens' precision was tested against a manometric transducer in five eye bank eyes. The second part examined pressure as a factor dependent on the appositional force, and the third part of the study investigated the correct procedure for measuring baseline eye pressure, p0. The instrument described here allows investigation of three examination parameters: (a) the measurement of p0, the pressure independent of the appositional force; (b) the continuous measurement of the intraocular pressure (IOP); (c) the measurement of the IOP dependent on the appositional force, including artificial IOP elevation.

Contact lens tonometry--application in humans.

PURPOSE: To establish a standard clinical procedure for measuring intraocular pressure (Po) with the contact lens tonometer (CLT), to demonstrate possibilities for analyzing ocular pulsation and performing ophthalmodynamometry. METHODS: A reliable histogram-based analyzing system for determining Po is used. First, the ocular pressure was registered with the CLT method and compared with the Goldmann applanation pressure, measured immediately beforehand. Second, ocular pulsation was studied by recording Po for 30 to 70 seconds, and the pulse amplitude was then analyzed. Third, an ophthalmodynamometry method during slit-lamp examination was tested. The central retinal artery was observed through the contact lens while the appositional force was elevated. A mark was set at the systolic and diastolic pressure while observing arterial pulsation (similar to the Korotkoff sounds). RESULTS: Compared with the Goldmann method measurements, Po obtained with the CLT method yielded a linear regression of r = 0.7 (right eye) and r = 0.68 (left eye), and was therefore highly significant (P < 0.0001, two-tailed). Analysis of the pulse amplitude showed great variability (range, 1 to 9 mm Hg; means, 2.9 mm Hg [right eye] and 3.0 mm Hg [left eye]). The dependence of the pulse amplitude on Po and age was shown with a correlation coefficient of r = 0.55 and r = 0.59, respectively. The difference between the right and left eye of the person was < 0.5 mm Hg. CONCLUSION: The CLT can be used during slit-lamp examination and permits tonometry during ophthalmoscopy, ocular pulsation assessment at different intraocular pressures, and ophthalmodynamometry.

Anti-insulin-like growth factor-I activity of a novel polysulphonated distamycin A derivative in human lung cancer cell lines.

1. The purpose of this study was to investigate the antiproliferative effect and the modulation of the mitogenic insulin-like growth factor-I (IGF-I) system by FCE 26644 and FCE 27784, two polyanionic sulphonated distamycin A derivative compounds, on two human non-small cell lung cancer (N-SCLC) cell lines. 2. For cell growth studies the colorimetric MTT and the thymidine incorporation assays were performed; the presence of IGF-I and IGF-binding proteins in conditioned media was revealed by radioimmunoassay and Western ligand blot, respectively. Variations at the IGF-I-receptor level were tested by binding studies on cell monolayers. 3. A significant concentration- and time-dependent cytostatic activity of FCE 26644 (IC50 approximately 200 micrograms ml-1 at 72 h) compared to its analogue FCE 27784 (IC50 > 800 micrograms ml-1) was observed in both cell lines studied. The IGF-I-stimulated proliferation of the IGF-I-responsive A549 cell line was abolished by 24 h of FCE 26644 treatment whereas FCE 27784 was inactive. FCE 26644 increased (4 to 6 fold) the secretion of IGF-I-like material and reduced the IGF-I binding (IC50 > 100 micrograms ml-1) in both A549 and Ca-Lu-1 cell lines. FCE 26644 (100 micrograms ml-1) did not affect the KD (approximately 0.5 nM) but reduced the Bmax and the number of receptor sites (50%). 4. Our findings demonstrate that the ability to down-regulate the cell proliferation of N-SCLC cell lines, shown by FCE 26644, depends at least partially, on interference with the "IGF-I mitogenic system'.

An unobtrusive system for helping a person with blindness and intellectual disability travel in indoor areas.

A system causing no environmental disturbance was employed for helping a woman with blindness and intellectual disability travel in indoor areas. The system provided encouragement and praise while the woman moved in the correct direction and a buzzer sound in the case of incorrect direction through earpieces. The results showed that the woman learned to use the system and traveled successfully.

Comparison between novel steroid-like and conventional nonsteroidal antioestrogens in inhibiting oestradiol- and IGF-I-induced proliferation of human breast cancer-derived cells.

1. This study has two specific aims: (a) to compare the antioestrogenic activity of two steroidal analogues of 17 beta-oestradiol, the 7 alpha-alkylamide, ICI 164,384 and the 7 alpha-alkylsulphinylamide, ICI 182,780, with that of the triphenylethylene-derived compound 4OH-tamoxifen on a pool of human breast cancer cell lines (HBCCL) with a range of hormonal responsiveness and acquired anti-oestrogen resistance and (b) to investigate the ability of such antioestrogens to modulate the potent breast carcinoma growth-stimulatory activity of the 'IGF-I system'. 2. For the chemosensitivity investigations we used a long-term colorimetric and the short-term thymidine incorporation assay; we analysed IGF-I in conditioned media by a radioimmunoassay, IGF-I mRNA in the cells by RT-PCR and molecular species of IGF-I-binding proteins, secreted in conditioned media, by Western ligand blot. IGF-I receptors were assayed on cell monolayers by binding studies and by Scatchard analysis, we calculated KD, Bmax and sites/cell. 3. Our results indicate that ICI 182,780 and ICI 164,384 are 1.5-5.5 fold more potent than 4OH-tamoxifen in inhibiting the basal proliferation of oestrogen-receptor positive (ER+) breast cancer cell lines. Moreover we demonstrate the capacity of ICI 182,780 and ICI 164,384 to reduce, in a time-dependent fashion, oestrogen- and/or IGF-I-stimulated growth of ER+cell lines, possibly by negatively interfering with an IGF-I-like material secretion and IGF-I-receptor number. 4. Our data provide the first evidence that, on ER+human breast carcinoma cell lines, steroidal antioestrogens inhibit cell growth and modulate the IGF-I mitogenic system. The mechanism of this latter effect has yet to be identified.

Suramin interferes with auto/paracrine insulin-like growth factor I-controlled proliferative loop on human lung cancer cell lines.

Human non-small cell lung cancer (N-SCLC), a common malignancy generally unmanageable by conventional cytotoxic chemotherapy, represents a major world health burden. Suramin, a polyanionic drug which appears to interfere with growth-factor/receptor interaction, has recently been shown to be cytostatic for small cell lung cancer cells; it may also be effective for N-SCLC. As insulin-like growth factor I (IGF-I) is a known progression agent for N-SCLC, we have examined the effects of suramin on the 'IGF-I system' in a panel of human N-SCLC cell lines. Colorimetric and thymidine incorporation assays were used to assess cell chemosensitivity whereas a radio-receptor assay was employed to evaluate IGF-I/receptor binding. Suramin reversibly reduced, in a concentration- and time-dependent manner, the growth of each N-SCLC cell line examined either cultured in serum-containing or serum-free medium. Furthermore, suramin caused a concentration-related inhibition of labeled IGF-I peptide specific binding on all cell lines studied. Suramin caused a significant reduction in the Bmax values with only weak variations in the affinity constants (Kd). We hypothesize that suramin interference with IGF-I mitogenic activity is a pathway by which this drug produces its effect in vitro. These data indicate further studies on the mechanism of action and pharmacology of suramin in vivo are warranted.

Expression and function of the insulin-like growth factor I system in human non-small-cell lung cancer and normal lung cell lines.

In order to analyze the presence and the function of the "insulin-like growth factor I (IGF-I) system" in human non-small-cell lung cancer (N-SCLC) we tested 5 cell lines of different histological sub-types: A549, Ca-Lu-6, SK-Lu-1 (adenocarcinoma); Ca-Lu-1, SK-Mes-1 (squamous carcinoma) and one normal fibroblast-like fetal lung cell line (IMR-90) for expression of the IGF-I peptide and its RNA transcribed from the IGF-I gene; IGF-binding proteins (IGF-BP); IGF-I receptor (IGF-I-R) and its mRNA. In addition, we examined the capacity of exogenous human recombinant IGF-I to enhance the in vitro cell proliferation. In medium conditioned from cell cultures, we detected immunoreactive IGF-I material by radioimmunoassay. Western ligand blot and affinity labelling demonstrated the presence of several molecular species of IGF-BPs (IGF-BP-4, -1, -2, -3) as well. Northern blot analysis of polyA+ RNA from all cell lines examined revealed the presence of IGF-I and IGF-I-R mRNA. Moreover, binding studies on cultured cell lines showed one class of high-affinity, operative type-I IGF cell-surface binding sites. Finally, by thymidine uptake and colorimetric metabolic MTT assays, we found that most neoplastic cell lines react mitogenically to IGF-I and that its physiological effect is abolished by an anti-IGF-I-receptor antibody. These data indicate the importance of the IGF-I system in N-SCLC growth. Furthermore, they suggest that this mitogenic complex should be appraised as a possible target for anti-neoplastic drugs, antibodies or growth-factor analogues offering potential new approaches to therapy.

Suramin-induced growth inhibition and insulin-like growth factor-I binding blockade in human breast carcinoma cell lines: potentially related events.

Suramin, a polyanionic drug used in the treatment of trypanosomiasis and onchocerciasis, inhibits growth factor-induced mitogenesis in several human tumours. We have investigated the effect of suramin on human breast cancer cell lines (HBCCL). By cell counts and thymidine incorporation we found that 50 to 400 micrograms/ml suramin inhibits the proliferation of HBCCL in a dose-dependent and reversible fashion (ID50 approximately 200 micrograms/ml for MCF-7 and MDA-MB 231). Radioreceptor and affinity cross-linking assays showed that suramin was also able to reduce the binding of insulin-like growth factor I (IGF-I) to its receptor (40-50% inhibition at 100 micrograms/ml). Our results indicate that the drug does not affect the IGF-I receptor (IGF-I-R), but binds directly to the IGF-I peptide. In conclusion, the strict correlation observed between suramin inhibition of proliferation and IGF-I binding on HBCCL suggests a possible therapeutic role for this molecule as an antineoplastic drug in human breast tumours.

Optical bistability by photothermal displacement in prism coupling into planar waveguides.

We have identified photothermal displacement as a mechanism for optical bistability (OB) in prism coupling into absorbing planar waveguides: heating by the absorbed incoupled power causes a buckling of the waveguide, a reduction in air-gap width, and thus an increase in incoupling efficiency and a positive feedback. We developed a theory of this OB that qualitatively agrees well with experimental results obtained by coupling argon-laser light into indium-tin oxide layers as strongly absorbing waveguides. This new OB is quite different from dispersive OB in prism or grating couplers caused by a power-dependent effective guide index.

Self-pulsing in prism coupling into planar waveguides.

Coupling argon-laser light into absorbing SiO(2)-TiO(2) waveguides, we observed at constant input power depending on the angle of incidence and the initial gap width, self-pulsing, bistability, or a special form of bistability with either a constant or a self-pulsing output. The system's dynamics is governed by two effects with different time constants, both caused by heating of the waveguide by the incoupled absorbed power: (1) thermal expansion of waveguide and prism, which reduces the coupling gap width and thus changes the incoupling efficiency, and (2) desorption of H(2)O molecules from the SiO(2)-TiO(2) layer, which changes the effective guide index.