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Biomedical subjects

A Marra

Publications and source records attributed to A Marra.

At least 19 recordsLinked to original sources
PubMed2006

Induction chemotherapy, concurrent chemoradiation and surgery for Pancoast tumour.

The traditional treatment of Pancoast tumour with local approaches (surgery, radiotherapy or a combination of both) leads to a poor outcome due to the high rate of incomplete resection and the lack of systemic control. The aim of the present prospective feasibility study was to determine whether a trimodality approach improves local control and survival. Patients with stage IIB-IIIB Pancoast tumour received induction chemotherapy (three courses of split-dose cisplatin and etoposide or paclitaxel) followed by concurrent chemoradiotherapy (a course of cisplatin/etoposide combined with 45 Gy hyperfractionated accelerated radiotherapy). After restaging, eligible patients underwent surgery 4-6 weeks post-radiation. A total of 31 consecutive patients with T3 (81%) or T4 (19%) Pancoast tumour were enrolled in the study. Induction chemoradiotherapy was completed in all patients without treatment-related deaths. Grade 3-4 toxicity was observed in 32% of cases. In total, 29 (94%) patients were eligible for surgery. Complete resection was achieved in 94% of patients. The post-operative mortality rate was 6.4% and major complications arose in 20.6% of the patients. The median survival was 54 months with 2- and 5-yr survival rates of 74 and 46%, respectively. In conclusion, this intensive multimodality treatment of Pancoast tumour is feasible and improves local resectability rates and long-term survival as compared with historical series.

Adult↗
PubMed2006

Whole genome expression analysis for biologic rational pathway modeling: application in cancer prognosis and therapy prediction.

Using semi-quantitative microarray technology, almost every one of the approximately 30 000 human genes can be analyzed simultaneously with a low rate of false-positives, a high specificity, and a high quantification accuracy. This is supported by data from comparative studies of microarrays and reverse-transcription PCR for established cancer genes including those for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2/ERBB2), estrogen receptor (ESR1), progesterone receptor (PGR), urokinase-type plasminogen activator (PLAU), and plasminogen activator inhibitor-1 (SERPINE1). As such, semi-quantitative expression data provide an almost completely comprehensive background of biological knowledge that can be applied to cancer diagnostics. In clinical terms, expression profiling may be able to provide significant information regarding (i) the identification of high-risk patients requiring aggressive chemotherapy; (ii) the pathway control of therapy predictive parameters (e.g. ESR1 and HER2); (iii) the discovery of targets for biologically rational therapeutics (e.g. capecitabine and trastuzumab); (iv) additional support for decisions about switching therapy; (v) target discovery; and (vi) the prediction of the course of new therapies in clinical trials. In conclusion, whole genome expression analysis might be able to determine important genes related to cancer progression and adjuvant chemotherapy resistance, especially in the context of new approaches involving primary systemic chemotherapy. In this review, we will survey the current progress in whole genome expression analyses for cancer prognosis and prediction. Special emphasis is given to the approach of combining biostatistical analysis of expression data with knowledge of biochemical and genetic pathways.

Cluster Analysis↗
PubMed2002

[Indication, type of resection and results of surgery in cases of lung tuberculosis. A historical and regional overview].

Pulmonary tuberculosis has become a rare indication for surgical intervention in all industrial nations. Over a period of 10 years we overview 193 patients who were suffering this disease and underwent thoracotomy. Main indication (79.8 %) was pulmonary nodules, of unknown origin. In this cases wedge resection was performed. Expanded resectional techniques were necessary in cases of cavernes, superinfected bronchiectasis, bronchial stenosis, hemoptysis and destroyed lungs due to tuberculosis. Considering the heterogenous groups of patients, the perioperative morbidity (21.8 %) and mortality (0.5 %) has to be regarded in comparison to the data found in the literature.

Developed Countries↗
PubMed2002

[Significance of pulmonary lymph node metastases in locally advanced non-small cell lung cancer].

BACKGROUND: The locally advanced (T3 - 4) non-small cell lung cancer with pulmonary lymph node metastases (N1) is a mixture of different subgroups of disease with varying pattern of tumor extension and long-term survival rates. PATIENTS AND METHODS: We retrospectively reviewed hospital records and follow-up data of 181 patients operated on between 1990 and 1995 with pathological stage IIIA-pT3N1 and IIIB-pT4N1. Median age was 62 years (range 34 - 80). RESULTS: The operative mortality was 3.7 %. The analysis was carried out on the 181 hospital survivors. The operative procedure was a pneumonectomy in 110 cases (60.8 %) and a lobectomy/bilobectomy in 71 (39.26 %). The pathological stage according to the UICC TNM-Classification of 1997 was T3N1 in 128 (70.7 %) and T4N1 in 53 (29.3 %). We observed a metastatic involvement of the hilar, interlobar and lobar lymph nodes in 44 (24.3 %), 17 (9.4 %), and 27 (14.9 %) patients, respectively, whereas a direct infiltration in 93 patients (51.4 %). The actuarial overall 3-, 5- and 10-year survival rates for N1 hilar was 23 %, 13 % and 8 %, for N1 interlobar was 18 %, 6 % and 0 %, for N1 lobar was 48 %, 37 % and 22 %, and for N1 direct was 32 %, 27 % and 21 %, respectively. The involvement of hilar lymph nodes correlates with a worse prognosis (p =.0366). CONCLUSIONS: Metastases to the hilar lymph nodes in locally advanced NSCLC can be considered an initial N2-disease and should be treated correspondingly. Lymph node involvement by direct invasion is associated with a relatively more favourable prognosis for the patients.

Actuarial Analysis↗
PubMed2001

Chemical synthesis of linear and cyclic unnatural oligosaccharides by iterative glycosidation of ketoses.

The development of an efficient method for the stereoselective synthesis of alpha-D-(2-->1)-linked ketoside oligomers is described. The method is based on an iterative protocol composed of two key steps: a) the coupling of a thiazolylketosyl phosphite donor with an hydroxymethylketoside acceptor; and b) the introduction of the hydroxy-methyl group at the anomeric carbon atom of the resulting oligomer. To highlight its efficiency, the protocol was used in the assembly of D-galacto-2-heptulopyranose-containing oligoketosides through alpha-(2-->1) linkages up to the pentameric stage. The yield of the isolated oligomers ranged from 48 % in the first cycle to 29% in the fourth cycle. Having employed a pentenyl-substituted hydroxymethylketoside acceptor in the first cycle, all the derived oligomers contained the pentenyl group at their reducing end. This group was exploited to transform the linear oligomers into cyclic products through intramolecular glycosidation. The major product derived from the linear trisaccharide was confirmed by X-ray crystallography to be the cyclotris-(2-->1)-(alpha-D-galacto-2-heptulopyranosyl). The structure of this compound was essentially that of a [9]crown-3 ether bearing three galactopyranose rings spiroanellated in a propellerlike fashion. This arrangement of carbohydrate units linked to the crown ether created a densely alkoxylated cavity suitable for the encapsulation of alkali-metal cations (Li, Na, K, Ca, Mg).

Carbohydrate Sequence↗
PubMed2001

Differential fluorescence induction reveals Streptococcus pneumoniae loci regulated by competence stimulatory peptide.

Differential fluorescence induction (DFI) in Streptococcus pneumoniae was used as a method for the discovery of genes activated in specific growth environments. Competence stimulatory peptide (CSP) was used as the model inducing system to identify differentially expressed genes. To identify CSP-induced promoters, a plasmid library was constructed by inserting random pieces of S. pneumoniae chromosomal DNA upstream of the promoterless gfpmut2 gene in an Escherichia coli/S. pneumoniae shuttle vector. S. pneumoniae carrying the library were induced with CSP and enriched for green fluorescent protein (GFP)-expressing bacteria using fluorescence-activated cell sorting. A total of 886 fluorescent clones was screened, and 12 differentially activated promoter elements were identified. Sequence analysis of these clones revealed that three were associated with novel competence loci, one of which we show is essential for DNA uptake, and six are known CSP-inducible promoters. We also explored whether competence proteins have a role in virulence and found that mutations in three CSP-inducible genes resulted in attenuated virulence phenotypes in either of two murine infection models. These results demonstrate the utility of DFI as a method for identifying differentially expressed genes in S. pneumoniae and the potential utility of applying DFI to other Gram-positive bacteria.

Animals↗
PubMed2001

A functional genomic analysis of type 3 Streptococcus pneumoniae virulence.

Streptococcus pneumoniae remains a serious cause of morbidity and mortality in humans, but relatively little is known about the molecular basis of its pathogenesis. We used signature-tagged mutagenesis together with an analysis of S. pneumoniae genome sequence to identify and characterize genes required for pathogenesis. A library of signature-tagged mutants was created by insertion-duplication mutagenesis, and 1786 strains were analysed for their inability to survive and replicate in murine models of pneumonia and bacteraemia. One hundred and eighty-six mutant strains were identified as attenuated, and 56 were selected for further genetic characterization based on their ability to excise the integrated plasmid spontaneously. The genomic DNA inserts of the plasmids were cloned in Escherichia coli and sequenced. These sequences were subjected to database searches, including the S. pneumoniae genome sequence, which allowed us to examine the chromosomal regions flanking these genes. Most of the insertions were in probable operons, but no pathogenicity islands were found. Forty-two novel virulence loci were identified. Five strains mutated in genes involved in gene regulation, cation transport or stress tolerance were shown to be highly attenuated when tested individually in a murine respiratory tract infection model. Additional experiments also suggest that induction of competence for genetic transformation has a role in virulence.

Amino Acid Sequence↗
PubMed2001

Completion pneumonectomy: current indications, complications, and results.

OBJECTIVE: Completion pneumonectomy is reported to be associated with high morbidity and mortality, especially when done in patients with benign disease. We review our 9 years of experience with this operation to evaluate the postoperative outcome and long-term results of various indications. METHODS: Between January 1990 and December 1998, 66 consecutive patients underwent completion pneumonectomy (6.8% of all pneumonectomies), and their cases were retrospectively reviewed. The indication was benign disease in 17 patients and malignant disease in 49 patients. In patients with malignant indications there were 14 local recurrences, 4 second primary tumors, 5 metastatic diseases, and 26 indications because of incomplete initial resection. RESULTS: There were no intraoperative deaths, and the postoperative mortality rate was 7.6%. Complications were encountered in 32 (53%) patients, without any significant difference between benign indication (71%) and malignant indication (47%; P =.0923). Bronchopleural fistula was encountered in 5 (7.6%) patients, and empyema was encountered in 7 (11%) patients. The actuarial 5-year survival was 57% for all patients, 65% for those with benign indications, and 54% for those with malignant indications (60% for local recurrence, 50% for second primary tumor, and 56% for incomplete resection), without any difference between benign and malignant indications (P =.9478). CONCLUSIONS: Completion pneumonectomy can be performed with acceptable mortality and morbidity, even in patients with benign disease. Patients with preoperative infection can be managed with bronchial stump covering and adequate postoperative drainage. Although complications are common, they can successfully be managed with a proper understanding of them.

Adult↗
PubMed2001

Decline of infant and child mortality rates in rural Senegal over a 37-year period (1963-1999).

BACKGROUND: In spite of an improving trend, childhood mortality in rural sub-Saharan Africa remains high and has recently risen in some countries. The factors associated with the long-term decline in childhood mortality are poorly known, due to a lack of data. METHODS: A Senegalese rural population has been under demographic surveillance since 1963. Infant and under-5 mortality rates were calculated for different periods to generate a long-term trend in childhood mortality. Evolution of age and seasonal patterns of mortality were observed. FINDINGS: During the observation period (1963-1999), infant and under-5 mortality rates decreased from 223 per thousand to 80 per thousand and 485 per thousand to 213 per thousand , respectively, with a constant annual rate of decline in the probability of dying since the 1960s (-3.7% and -3.1%, respectively). The age pattern of the under-5 mortality changed drastically, with a large decrease in the death rate between 6 and 24 months of age (from 321 per thousand to 87 per thousand ). This change took place during the 1970s. The seasonal variation, characterized by a greater proportion of deaths during the rainy season, was very marked during the 1960s, then decreased during the 1980s but it has tended to increase again in the 1990s, particularly among children 1-4 years old. CONCLUSION: This study confirms the long-term trend of decrease in child mortality in rural West Africa. Historical knowledge on healthcare developments suggests that immunizations have contributed to the decrease and the change in the age pattern. The re-emergence of malaria seems the most likely explanation for the recent rebound in seasonal variation. Attention to immunization and malaria should continue to be a priority.

Age Distribution↗
PubMed2001

rho is not essential for viability or virulence in Staphylococcus aureus.

We have identified the gene for transcription termination factor Rho in Staphylococcus aureus. Deletion of rho in S. aureus reveals that it is not essential for viability or virulence. We also searched the available bacterial genomic sequences for homologs of Rho and found that it is broadly distributed and highly conserved. Exceptions include Streptococcus pneumoniae, Streptococcus pyogenes, Mycoplasma genitalium, Mycoplasma pneumoniae, Ureaplasma urealyticum, and Synechocystis sp. strain PCC6803, all of which appear not to possess a Rho homolog. Complementation studies indicate that S. aureus Rho possesses the same activity as Escherichia coli Rho and that the Rho inhibitor bicyclomycin is active against S. aureus Rho. Our results explain the lack of activity of bicyclomycin against many gram-positive bacteria and raise the possibility that the essentiality of rho may be the exception rather than the rule.

Amino Acid Sequence↗
PubMed2001

Streptococcus pneumoniae causes experimental meningitis following intranasal and otitis media infections via a nonhematogenous route.

Using two different animal models of Streptococcus pneumoniae infection, we have demonstrated that this organism is able to spread to the central nervous system and cause meningitis by bypassing the bloodstream. Following respiratory tract infection induced via intranasal inoculation, bacteria were rapidly found in the bloodstream and brains in the majority of infected mice. A similar pattern of dissemination occurred following otitis media infection via transbullar injection of gerbils. However, a small percentage of animals infected by either route showed no bacteria in the blood and yet did have significant numbers of bacteria in brain tissue. Subsequent experiments using a galU mutant of S. pneumoniae, which is impaired in its ability to disseminate to the bloodstream following infection, showed that this organism is able to spread to the brain and cerebrospinal fluid. These results demonstrate that, unlike many bacterial pathogens that cause meningitis, S. pneumoniae is able to do so independent of bloodstream involvement upon different routes of infection. This may address the difficulty in treating human infections caused by this organism.

Animals↗
PubMed2001

[Pleomorphic adenoma of the parotid gland in childhood].

BACKGROUND: The authors report the results of ten years' activity at the Pedodontic Surgery Unit in the Institute of Maxillofacial Surgery at the Second University of Naples and analyse the possibility of conservative treatment of pleomorphic adenoma in childhood. METHODS: The study includes 614 cases of salivary gland pathology. The authors illustrate the epidemiological, clinical and therapeutic characteristics of this type of lesion in childhood, emphasising that the data emerging from this study do not differ from the clinical and therapeutic management of pleomorphic adenoma in young patients reported in the literature. RESULTS: In particular, they emphasise that satisfactory therapeutic results can be achieved using conservative techniques, like conservative superficial parotidectomy. CONCLUSIONS: Conservative superficial parotidectomy has the advantage of being less radical and traumatic for a young patient, without provoking a significant increase in recidivation.

Adenoma, Pleomorphic↗
PubMed2000

A genomic analysis of two-component signal transduction in Streptococcus pneumoniae.

A genomics-based approach was used to identify the entire gene complement of putative two-component signal transduction systems (TCSTSs) in Streptococcus pneumoniae. A total of 14 open reading frames (ORFs) were identified as putative response regulators, 13 of which were adjacent to genes encoding probable histidine kinases. Both the histidine kinase and response regulator proteins were categorized into subfamilies on the basis of phylogeny. Through a systematic programme of mutagenesis, the importance of each novel TCSTS was determined with respect to viability and pathogenicity. One TCSTS was identified that was essential for the growth of S. pneumoniaeThis locus was highly homologous to the yycFG gene pair encoding the essential response regulator/histidine kinase proteins identified in Bacillus subtilis and Staphylococcus aureus. Separate deletions of eight other loci led in each case to a dramatic attenuation of growth in a mouse respiratory tract infection model, suggesting that these signal transduction systems are important for the in vivo adaptation and pathogenesis of S. pneumoniae. The identification of conserved TCSTSs important for both pathogenicity and viability in a Gram-positive pathogen highlights the potential of two-component signal transduction as a multicomponent target for antibacterial drug discovery.

Animals↗
PubMed2000

Lactic acidosis and antiretroviral therapy: a case report and literature review.

Antiretrovirals, particularly nucleoside analogue reverse transcriptase inhibitors (RTIs) - DDI, 3TC and D4T, are widely used to effectively control human immunodeficiency virus (HIV) infection. These drugs have several adverse effects including anemia, peripheral neuropathy, pancreatitis and, on rare occasions, lactic acidosis. We describe the case of a 39 year old patient who had severe lactic acidosis after receiving stavudine (D4T) and didanosine (DDI) for an 8 month period. She had never manifested an opportunistic infection and presented a CD4 count of 378 cells/mm3 and an undetectable viral load (< 400 copies/ml). The purpose of the following report is to alert clinicians and infectious diseases specialists to the occurrence of lactic acidosis in asymptomatic HIV patients receiving antiretrovirals for long periods of time.

Acidosis, Lactic↗
PubMed2000

Genetic characterization of gram-positive homologs of the XerCD site-specific recombinases.

Homologs of the XerCD enzymes, which in Escherichia coli have been shown to be responsible for resolving chromosomal multimers prior to chromosome segregation, were identified in the genomes of Staphylococcus aureus and Streptococcus pneumoniae. Phylogenetic and conservation pattern analysis suggests that the S. aureus gene products are orthologs of XerC and D. A S. aureus xerC null mutant displayed in vitro characteristics consistent with the segregation defect reported for E. coli xer mutants, and was found to be attenuated in a murine infection model. Strikingly, the S. aureus xerD gene appears to be absolutely required for viability, and may therefore be the first example of an essential gene of the lambda integrase family. In contrast, phylogenetic and conservation pattern analysis show that the S. pneumoniae gene products are more closely related to phage integrases than to XerCD. S. pneumoniae xer1, 2 and 3 null mutants were each found to be attenuated in a murine infection model, suggesting that they may control processes which affect virulence.

Alleles↗
PubMed1999

Computerised counting of tumour infiltrating lymphocytes in 90 breast cancer specimens.

Tumour infiltrating lymphocytes (TILs) implicated in immunologic cytotoxicity were evaluated by immunohistochemistry and digitally counted in serial sections from 90 breast cancers in order to assess their number, the relationships between them and to tumour histology. CD3+, CD4+, CD8+, CD20+, CD25+ and CD56+ lymphocytes were found in 58 (64.4%), 52 (57.7%), 50 (55.5%), 22 (24.4%), 11 (12.2%) and 21 (23.3%) tumours, respectively. There was no difference in the number of TILs between pure infiltrating ductal (NOS) and non-ductal carcinomas, and no relationship between TILs and histological grades was found. CD3+ TILs directly correlated to age, while lymph node negative patients had tumours infiltrated by fewer CD4+ TILs with respect to lymph node positive patients. In 25/90 patients, randomly chosen, the status of peripheral blood lymphocytes was evaluated but no differences with respect to the status found in healthy blood donors was obtained; nonetheless while in some patients CD8+ TILs outnumbered CD4+ TILs in situ, the CD4/CD8 ratio was normal in their peripheral blood. The results show a considerable diversity of TILs among breast tumours, their lack of relationship with the status of the peripheral blood cells, and their potential important relationship with age (CD3+) and lymph node status (CD4+).

Adult↗
PubMed1999

Malignant optic glioma of adulthood. Case report and review of the literature.

INTRODUCTION: The malignant optic glioma in adulthood is a rare tumour of middle-age which causes an early loss of vision and always leads to death within a year. CASE REPORT: The authors report a case of this disease in a 68-year-old woman with a history of rapidly deteriorating vision and death 6 months after surgery. CONCLUSION: A review of the previous cases showed the accordance of these with the syndrome defined first by Hoyt et al. in 1973; a statistical analysis reveals that the radiotherapy improves the survival whereas the role of chemotherapy is still not definite.

Aged↗