Levobupivacaine 0.75% vs. lidocaine 4% for topical anaesthesia: a clinical comparison in cataract surgery.

BACKGROUND: The aim of this study was to compare the efficacy of topical levobupivacaine drops 0.75% vs. lidocaine drops 4% in cataract surgery. METHODS: We examined 203 patients undergoing cataract surgery by phacoemulsification. They were randomized into two groups: one received four drops of lidocaine 4% and the other received four drops of levobupivacaine 0.75%. The onset and offset times of sensory block were evaluated. Application, intraoperative and postoperative subjective pain was quantified by the patients using a verbal pain score. Complications, rates of supplemental anaesthesia, and the satisfaction of surgeon and patients were also recorded. RESULTS: The mean sensory onset and offset times were significantly higher for the levobupivacaine group (P < 0.01). Pain score was lower in the levobupivacaine group than in the lidocaine one and the difference was statistically significant at all stages (P < 0.01). The mean satisfaction scores of patients and surgeon were also statistically higher for levobupivacaine (P < 0.01). No significant differences for complications and rates of supplemental anaesthesia were found. CONCLUSIONS: Topical levobupivacaine 0.75% shows the same efficacy and safety as lidocaine 4% in cataract surgery by phacoemulsification. There was an adequate block with a good level of satisfaction of surgeon and patients. Levobupivacaine 0.75% offers a new and acceptable choice for topical anaesthesia in cataract surgery.

[Vigilance on health surveillance in wood sector]. / Vigilanza sulla sorveglianza sanitaria nel settore legno.

OBJECTIVES: A program to promote occupational health among wood dust workers in the district of Civitavecchia. METHODS: In recent years, occupational health physicians charged of medical surveillance of wood workers (Competent Physicians, CPs) had been invited to perform a peer-review of their methods and activities. In the present phase, CPs have been invited to show the result of their medical surveillance. RESULTS: One hundred forty seven wood workers were submitted to rhinoscopic examination. The prevalence of woodwork-related rhinitis and other pathologic signs, including nasal adenocarcinoma (one case), was 32.7%. The prevalence of rhinitis in woodworkers increased with years of working as a woodworker. CONCLUSION: Wood dust and chemical exposures in wood workers represent a serious risk of disease for the nasal cavity and paranasal sinuses.

Efficacy and comparison of 0.5% levobupivacaine with 0.75% ropivacaine for peribulbar anaesthesia in cataract surgery.

BACKGROUND AND OBJECTIVE: The low cardiovascular and neurological toxicity of levobupivacaine has led to its application as a local anaesthetic in a wide variety of specialist applications including peribulbar block for cataract surgery. The aim of this study was to evaluate the efficacy of levobupivacaine 0.5% and to compare block quality vs. ropivacaine 0.75% in peribulbar anaesthesia. METHODS: We examined 208 patients subjected to cataract surgery by phacoemulsification who were randomized into two groups according to the anaesthetic used for peribulbar block, namely levobupivacaine 0.5% or ropivacaine 0.75%, both with the addition of hyaluronidase. Nerve block was carried out by injection of 6 mL of the anaesthetic mixture equally distributed between the inferotemporal and superonasal areas. The success of the block was evaluated by determining the time of motor and sensory onset, akinesia score, times of motor and sensory offset and satisfaction of the patient and surgeon after 24 h. Pre-block, post-block and postoperative intraocular pressure as well as the duration of surgical intervention was also determined. RESULTS: With respect to ropivacaine, levobupivacaine showed a significant reduction (P < 0.001) in the average motor and sensory onset. Both the akinesia score (P < 0.01) and mean motor and sensory offset times were also higher (P < 0.001). Neither the average intervention times nor the satisfaction of the patient/surgeon showed any significant differences between the two groups. CONCLUSIONS: Levobupivacaine (0.5%) has better anaesthetic properties with respect to 0.75% ropivacaine and is well-suited for peribulbar block in cataract surgery.

Repertoire breadth of human CD4+ T cells specific for HIV gp120 and p66 (primary antigens) or for PPD and tetanus toxoid (secondary antigens)

Antigen derived peptides bound on MHC class II molecules on presenting cells stimulate specific CD4 lymphocytes that are in a naive state if antigen is given for the first time, or in a memory state if antigen has been previously encountered. In order to compare clonal heterogeneity of the human CD4+ T helper repertoire in primary vs. recall responses, we have generated T cell lines in vitro by repeated stimulation of peripheral lymphocytes with primary or with recall antigens. Clonal heterogeneity was broad in the case of recall response to tetanus toxoid or PPD, with a high frequency of specific precursors (> 100 cells/10(6) lymphocytes). In contrast, T cell lines responsive to primary antigens (HIV gp120 or HIV p66) were oligoclonal as defined by TCR V beta gene usage and by spectratyping, and the precursor frequency was low (< 2 cells/10(6) lymphocytes). Primary T cell lines generated from blood samples drawn at different times from the same donor showed that clones with identical TCR CDR3 region coding sequences were expanded, suggesting that in these individuals a large progeny derived from one single precursor is present, even though a previous encounter with the antigen was not documented. Assuming an even in vivo distribution of such cells, the presence of one precursor every 10(6) CD4 lymphocytes (within the CD4 T repertoire that comprises roughly 10(11) CD4 T cells) indicates that approximately 10(5) identical T cells from the same clonal precursor account for the primary response against the model antigens we have studied.

Human T leukaemia virus type 1 (HTLV-1) specific T-helper cell response: clonal fluctuations and repertoire heterogeneity.

The naive T-helper (Th) repertoire specific for HTLV-1 envelope (env) has been examined on antigen specific T-cell lines and clones from non-immune individuals. Clonal heterogeneity was determined by analysing the T-cell receptor (TCR) Vbeta gene usage and by sequencing the hypervariable regions of the TCR genes. Fluctuations in the V beta gene usage were determined by comparing the TCR Vbeta gene profiles of T-cell lines at different times. We found that a diverse repertoire for HTLV-1 env could be triggered in vitro. Diverse Vbeta genes were used by the same line tested at different times, suggesting that clonal composition of an antigen-specific T-cell line is not constant in vitro. Clones in fact may be up- and down-regulated and clonotypes undetectable at one time point can emerge upon subsequent restimulation. Therefore evaluation of the clonal composition of a T-cell line gives a snapshot of the dominant clones at the time of analysis, and does not tell the whole picture of the antigen-specific ensemble. Furthermore, by sequencing the TCR genes, we identified clones with identical Vbeta gene usage which differed in hypervariable regions (CDR3), indicating their derivation from independent precursors and contributing to overall clonal heterogeneity. If these data can be extended to HTLV-1-infected patients studied in vivo, the Th cell repertoire specific for HTLV-1 env may prove very heterogenous, with important implications for vaccine development.

Handling of retroviral antigens by human antigen-presenting cells.

Antigen-specific T helper cells play an important role in retroviral infections. Indeed, they provide help for B-cell activation and antibody production and for clonal expansion of cytolytic lymphocytes. Therefore, we used retrovirus-specific human T helper clones in order to define modes of antigen presentation, antigen-presenting cells and the molecular context of Th epitopes that could be exploited in the design of immunogens aimed at optimizing the Th cell response. In particular, we describe several mechanisms of receptor-mediated antigen uptake that enhance the stimulation of human T-cell clones specific for HIV and HTLV-1 antigens; we report on the differential recognition of Th epitopes depending on the molecular-viral context; we show that dendritic cells are the most efficient presenting cells and are essential for the induction of in vitro primary Th cell responses; and finally, we propose that Th cells specific for internal, conserved antigens of HIV such as reverse transcriptase, may be candidates for intrastructural help resulting in induction of envelope specific antibodies.

Human CD4+ T cells can discriminate the molecular and structural context of T epitopes of HIV gp120 and HIV p66.

CD4+ T cell lines and clones specific for human immunodeficiency virus (HIV) antigens have been generated from peripheral lymphocytes of naive individuals by priming with the envelope protein gp120, the enzyme reverse transcriptase (p66), and their synthetic peptides. T cells were tested for proliferation to proteins, to peptides, and to HIV virions. Different patterns of reaction were identified. T cells primed in vitro with the whole antigen responded to the protein, but recognition of overlapping peptides occurred with a fraction of the lines or clones. The virus was recognized by some, but not all, of the gp120- and p66-specific T cells, with an efficiency 2 logs higher than the recombinant soluble proteins on a molar basis. One T cell line specific for gp120 responded to virions presented by B cells, but not by monocytes. In contrast, T cells induced with peptides did not always respond to the proteins. Generation of T cell lines from naive individuals may be an in vitro model for T cell immunization, and the response patterns may have implications for the design of vaccines aimed at inducing a T helper response. In fact our in vitro data suggest that (a) immunization with peptides does not always induce T cells recognizing the whole protein, (b) immunization with proteins does not always induce T cells recognizing the protein in the context of the HIV virus, and (c) recognition of gp120 in the context of HIV may be dictated by the type of presenting cells.

Recognition of human T-leukemia virus (HTLV-1) envelope by human CD4+ T-cell lines from HTLV-1 seronegative individuals: specificity and clonal heterogeneity.

Because T-helper cells are critical for immune responses in retroviral infections, CD4+ T-cell lines specific for the human T-leukemia virus type 1 (HTLV-1) envelope have been generated from peripheral T lymphocytes of nonimmune donors to study their naive repertoire. Recombinant fragments (RE1, amino acids [aa] 26-200; RE3, aa 165-307; RE5, aa 308-401; and RE6, aa 165-401) of HTLV-1 envelope, whole envelope glycoprotein, and synthetic peptides were used to induce T-cell lines. CD4+ T-cell lines specific for one or more fragments were obtained from seven of eight individuals tested. T-cell lines generated against envelope glycoprotein from five of five donors did not cross-react with the RE fragments and vice versa. The lines specific for RE and env were mapped with overlapping peptides. The lines with single peptide (narrow) specificity contained a variety of clones that used different T-cell receptor V beta genes. These data (1) suggest that most of the normal individuals carry T-helper precursors specific for epitopes on HTLV-1 envelope; (2) indicate that heterogeneity of HTLV-1 envelope-specific T cells can be detected in the naive repertoire; and (3) define optimal antigenic preparations to be used to assess cellular immunity in HTLV-1-infected individuals.

Nucleolar localisation of three Hox homeoproteins.

Homeoproteins encoded by genes of the Hox family are nuclear proteins believed to act as transcription factors and to participate in the determination of the body plan. Here we show that in several vertebrate cells, they exhibit a subnuclear localisation associated with the nucleolus. We used monoclonal antibodies to study the distribution of three homeoproteins, namely HOXB7, HOXC6 and HOXD4. The immunoreactivity to antibodies against HOXC6 protein in Xenopus laevis embryonic tissues is restricted to one or two spots within the nucleus; this distribution partially overlaps that of fibrillarin, a protein of the fibrillar zone of the nucleoli. Indirect immunofluorescence analysis of the distribution of HOXB7 protein in 3T3 cells, and of HOXD4 protein in human neuroblastoma and Raji lymphoma cell lines and activated lymphocytes, results invariably in a nucleolar localisation. Purified nucleoli from stimulated T lymphocytes, and Raji cells contain an activity capable of binding, in a gel retardation assay, to an oligonucleotide specifically recognised by the HOXD4 homeoprotein. This activity is specifically removed by anti-HOXD4 antibodies and is found associated in southwestern blots with a single band with an apparent M(r) of 30,000, corresponding to that of recombinant HOXD4. The functional significance of the nucleolar localisation of Hox proteins remains to be determined.

The homeotic gene products in the control of cell differentiation and proliferation.

Embryo development is controlled by a successive series of genes that provide each cell in the growing embryo with precise position information. Knowledge of these genes is known most completely from Drosophila, where a simple initial pattern generated by maternal effect genes is gradually segmented by the sequential transient expression of three successive series of genes: the gap genes, the pair-rule genes, and the segment polarity genes. Superimposing their action on the preexisting segments, these homeotic genes cause unique and often very distinctive patterns of differentiation for different segments. In humans, about 40 homeotic genes have been identified and are grouped into four clusters on chromosomes 2, 7, 12, and 17, whose organization reflects their spatial and temporal expression. Several homeotic genes have been found expressed not only in embryonic tissues, but also in adult tissues, most notably in the hematopoietic lineage, and also in tumors, especially leukemia, teratocarcinoma, and neuroblastoma, wherein their expression pattern is modified in a complex manner by retinoic acid. The target genes of the transcription factors encoded by the homeotic genes are largely unknown, but recent reports indicate that they may regulate the expression of adhesion molecules on the membrane and the production of components of the extracellular matrix. Abnormal expression of these genes can therefore affect not only cell proliferation, but also the spread of cells to aberrant locations.

[Diagnostic echography in tumefactions of the parotid space]. / Ecografia diagnostica nelle tumefazioni della loggia parotidea.

The reliability of the echographic approach to the diagnosis of expansive lesions of the parotid area has been evaluated by comparing in 45 patients the echographic data with the results of the clinical and/or histopathological investigations. There was a satisfactory agreement between conclusions based on the two approaches. In particular, echography was able to differentiate between: (a) intra- and extraglandular nodules; (b) diffuse and focal involvement of the gland and, (c) malignant and nonmalignant proliferative processes.