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Papers by Laurence Paolozzi

Research paper thumbnail of Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis

Annals of the Rheumatic Diseases, 2004

To evaluate long term efficacy of three iterative courses of three weekly intra-articular (IA) in... more To evaluate long term efficacy of three iterative courses of three weekly intra-articular (IA) injections of NRD101 in the treatment of symptomatic knee osteoarthritis (OA). Patients and methods: A 1 year prospective, multicentre, randomised, double blind, placebo controlled study of 301 patients aged .50 years with painful and radiological medial knee OA. Patients were randomly assigned into three groups receiving: (1) three courses of three IA injections of hyaluronic acid (HA) + oral placebo; (2) IA injections of saline solution + diacerein 100 mg/day; (3) IA injections of saline solution + oral placebo. Demographic data and symptomatic criteria-pain, Lequesne's index, patient's global assessment of disease activity, percentage of painful days-were obtained during the study; primary structural criterion was JSW. Efficacy criteria were changes in pain VAS, joint space narrowing (JSN), and percentage of progressors (JSN .0.5 mm). An intention to treat analysis was used for symptomatic variables, and completer analysis for structural variables. Results: Baseline characteristics were similar between the three groups. Mean (SD) improvement in pain VAS was clinically relevant (233.9 (27.3), n = 301), but with no difference between the groups (p = 0.96). JSW deteriorated (20.09 (0.55) mm, n = 277, p = 0.01), but with no difference between the groups (p = 0.82). Percentages of progressors were 17.7, 18.9, and 20.3% (p = 0.90), in groups 1, 2, and 3, respectively. Conclusion: A weak but statistically significant structural deterioration occurred over 1 year, together with clinically relevant symptomatic improvement in patients receiving oral drug and iterative IA injections. Symptomatic and/or structural effects for both this new HA compound and diacerein were not demonstrated.

Research paper thumbnail of Etanercept 50 mg once weekly improves patient-reported outcomes in patients with moderate-to-severe plaque psoriasis (Abstract)

Research paper thumbnail of Etanercept in the longterm treatment of patients with ankylosing spondylitis

The Journal of rheumatology, 2009

To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing spondylitis ... more To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing spondylitis (AS).

Research paper thumbnail of Once weekly administration of etanercept 50 mg is efficacious and well tolerated in patients with moderate-to-severe plaque psoriasis: a randomized controlled trial with open-label extension

British Journal of Dermatology, 2008

This study is particularly timely given a lawsuit in California that resulted in a requirement th... more This study is particularly timely given a lawsuit in California that resulted in a requirement that companies making coal tar products should place a statement warning that the product contains chemicals known to the State of California to cause skin cancer. The study reinforces an older long-term study of patients treated for psoriasis and eczema with tar and UVB at the Mayo Clinic. 1 That study also did not show an increase in skin cancers. M. Lebwohl, MD

Research paper thumbnail of CONCISE REPORTS Variability in knee radiographing: implication for

definition of radiological progression in medial knee osteoarthritis

Research paper thumbnail of Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis

Annals of the Rheumatic Diseases, 2006

Research paper thumbnail of Restoration of ligase activity in E. coli K12 lig ts7 strain by bacteriophage Mu and cloning of a DNA fragment harbouring the Mu ‘lig’ gene

Nucleic Acids Research, 1980

Restoration of ligase activity has been observed in E. coli K12 ligts7 strain lysogenic for Mu, i... more Restoration of ligase activity has been observed in E. coli K12 ligts7 strain lysogenic for Mu, in presence as well in absence of lysogenic immunity. This restoration consist in phenotypic reversal of temperature sensitivity of E. coli ligts7 which also regain the ability to sustain the complete growth cycle of T4 lig-phages. It is possible to put under the control of the gal operon the expression of the viral gene responsible for the restoration effect. This new gene of Mu has been named 'lig'. A 5 kb fragment responsible for the reported effects and localized between genes gam and lys of Mu genome has been cloned in pBR322. This recombinant plasmid used for transforming ligts7 strain restores in it normal behaviour for ligation of Okazaki pieces.

Research paper thumbnail of Two classes of Mu lig mutants: the thermosensitives for integration and replication and the hyperproducers for ligase

Nucleic Acids Research, 1980

We have previously shown that Mu restores an active DNA replication at non-permissive temperature... more We have previously shown that Mu restores an active DNA replication at non-permissive temperature in E. coli K12 Iigts7 strains. In this paper we describe two new types of phage mutants for the Mu lig function. The Mu ligts mutants are conditional lethals defective for both integration and replication of DNA, unable to 'complement' the bacterial lig mutation; they map between B and lys. The mutants of the other type, on the other hand, are able to restore to a maximum level the activity impaired by the Iigts7 mutation in the host. We suggest the hypothesis that the product of Mu lig gene could be part of a complex as a topoisomerase.

Research paper thumbnail of Recommendations for an update of 2003 European regulatory requirements for registration of drugs to be used in the treatment of RA

Current Medical Research and Opinion, 2011

Since 2003, the European Medicines Agency (EMA) document, &am... more Since 2003, the European Medicines Agency (EMA) document, 'Points to consider on clinical investigation of medicinal products other than NSAIDs (nonsteroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis' has provided guidance for the clinical development of both biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). In the last few years, several new products have been developed or are in development for the treatment of RA, which offer significant efficacy with regard to disease control, including prevention of structural damage and disability. Concurrently, novel insights have been gained with respect to the assessment of disease activity, joint damage and disability. New treatment strategies have been established which relate to early therapy, tight control and rapid switching of medication. Accordingly, several new EULAR/ACR recommendations have been or are being developed. Several important additions and changes are needed in the 2003 guidance to incorporate the current scientific knowledge into clinical trial design for the development of future products. Under the auspices of the Group for the Respect of Ethics and Excellence in Science (GREES), a group of experts in the field of RA and clinical trial design met to provide a consensus recommendation for an update to the 2003 EMA guidance document.

Research paper thumbnail of Clinical profile, contemporary management and one-year mortality in patients with severe acute heart failure syndromes: The EFICA study☆

European Journal of Heart Failure, 2006

Little is known about the epidemiology of acute decompensated heart failure (ADHF) in patients ad... more Little is known about the epidemiology of acute decompensated heart failure (ADHF) in patients admitted to intensive and coronary care units (ICU/CCU). Observational data may improve disease management and guide the design of clinical trials.

Research paper thumbnail of Recommendations for an update of 2003 European regulatory requirements for registration of drugs to be used in the treatment of RA

Current Medical Research and Opinion, 2011

Since 2003, the European Medicines Agency (EMA) document, &am... more Since 2003, the European Medicines Agency (EMA) document, 'Points to consider on clinical investigation of medicinal products other than NSAIDs (nonsteroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis' has provided guidance for the clinical development of both biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). In the last few years, several new products have been developed or are in development for the treatment of RA, which offer significant efficacy with regard to disease control, including prevention of structural damage and disability. Concurrently, novel insights have been gained with respect to the assessment of disease activity, joint damage and disability. New treatment strategies have been established which relate to early therapy, tight control and rapid switching of medication. Accordingly, several new EULAR/ACR recommendations have been or are being developed. Several important additions and changes are needed in the 2003 guidance to incorporate the current scientific knowledge into clinical trial design for the development of future products. Under the auspices of the Group for the Respect of Ethics and Excellence in Science (GREES), a group of experts in the field of RA and clinical trial design met to provide a consensus recommendation for an update to the 2003 EMA guidance document.

Research paper thumbnail of A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and Efficacy of Etanercept 25 Twice Weekly in Patients with Severe Persistent Asthma

Research paper thumbnail of Variability in knee radiographing: implication for definition of radiological progression in medial knee osteoarthritis

Annals of the Rheumatic Diseases, 1998

Research paper thumbnail of Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis

Annals of the Rheumatic Diseases, 2004

To evaluate long term efficacy of three iterative courses of three weekly intra-articular (IA) in... more To evaluate long term efficacy of three iterative courses of three weekly intra-articular (IA) injections of NRD101 in the treatment of symptomatic knee osteoarthritis (OA). Patients and methods: A 1 year prospective, multicentre, randomised, double blind, placebo controlled study of 301 patients aged .50 years with painful and radiological medial knee OA. Patients were randomly assigned into three groups receiving: (1) three courses of three IA injections of hyaluronic acid (HA) + oral placebo; (2) IA injections of saline solution + diacerein 100 mg/day; (3) IA injections of saline solution + oral placebo. Demographic data and symptomatic criteria-pain, Lequesne's index, patient's global assessment of disease activity, percentage of painful days-were obtained during the study; primary structural criterion was JSW. Efficacy criteria were changes in pain VAS, joint space narrowing (JSN), and percentage of progressors (JSN .0.5 mm). An intention to treat analysis was used for symptomatic variables, and completer analysis for structural variables. Results: Baseline characteristics were similar between the three groups. Mean (SD) improvement in pain VAS was clinically relevant (233.9 (27.3), n = 301), but with no difference between the groups (p = 0.96). JSW deteriorated (20.09 (0.55) mm, n = 277, p = 0.01), but with no difference between the groups (p = 0.82). Percentages of progressors were 17.7, 18.9, and 20.3% (p = 0.90), in groups 1, 2, and 3, respectively. Conclusion: A weak but statistically significant structural deterioration occurred over 1 year, together with clinically relevant symptomatic improvement in patients receiving oral drug and iterative IA injections. Symptomatic and/or structural effects for both this new HA compound and diacerein were not demonstrated.

Research paper thumbnail of Etanercept 50 mg once weekly improves patient-reported outcomes in patients with moderate-to-severe plaque psoriasis (Abstract)

Research paper thumbnail of Etanercept in the longterm treatment of patients with ankylosing spondylitis

The Journal of rheumatology, 2009

To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing spondylitis ... more To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing spondylitis (AS).

Research paper thumbnail of Once weekly administration of etanercept 50 mg is efficacious and well tolerated in patients with moderate-to-severe plaque psoriasis: a randomized controlled trial with open-label extension

British Journal of Dermatology, 2008

This study is particularly timely given a lawsuit in California that resulted in a requirement th... more This study is particularly timely given a lawsuit in California that resulted in a requirement that companies making coal tar products should place a statement warning that the product contains chemicals known to the State of California to cause skin cancer. The study reinforces an older long-term study of patients treated for psoriasis and eczema with tar and UVB at the Mayo Clinic. 1 That study also did not show an increase in skin cancers. M. Lebwohl, MD

Research paper thumbnail of CONCISE REPORTS Variability in knee radiographing: implication for

definition of radiological progression in medial knee osteoarthritis

Research paper thumbnail of Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis

Annals of the Rheumatic Diseases, 2006

Research paper thumbnail of Restoration of ligase activity in E. coli K12 lig ts7 strain by bacteriophage Mu and cloning of a DNA fragment harbouring the Mu ‘lig’ gene

Nucleic Acids Research, 1980

Restoration of ligase activity has been observed in E. coli K12 ligts7 strain lysogenic for Mu, i... more Restoration of ligase activity has been observed in E. coli K12 ligts7 strain lysogenic for Mu, in presence as well in absence of lysogenic immunity. This restoration consist in phenotypic reversal of temperature sensitivity of E. coli ligts7 which also regain the ability to sustain the complete growth cycle of T4 lig-phages. It is possible to put under the control of the gal operon the expression of the viral gene responsible for the restoration effect. This new gene of Mu has been named 'lig'. A 5 kb fragment responsible for the reported effects and localized between genes gam and lys of Mu genome has been cloned in pBR322. This recombinant plasmid used for transforming ligts7 strain restores in it normal behaviour for ligation of Okazaki pieces.

Research paper thumbnail of Two classes of Mu lig mutants: the thermosensitives for integration and replication and the hyperproducers for ligase

Nucleic Acids Research, 1980

We have previously shown that Mu restores an active DNA replication at non-permissive temperature... more We have previously shown that Mu restores an active DNA replication at non-permissive temperature in E. coli K12 Iigts7 strains. In this paper we describe two new types of phage mutants for the Mu lig function. The Mu ligts mutants are conditional lethals defective for both integration and replication of DNA, unable to 'complement' the bacterial lig mutation; they map between B and lys. The mutants of the other type, on the other hand, are able to restore to a maximum level the activity impaired by the Iigts7 mutation in the host. We suggest the hypothesis that the product of Mu lig gene could be part of a complex as a topoisomerase.

Research paper thumbnail of Recommendations for an update of 2003 European regulatory requirements for registration of drugs to be used in the treatment of RA

Current Medical Research and Opinion, 2011

Since 2003, the European Medicines Agency (EMA) document, &am... more Since 2003, the European Medicines Agency (EMA) document, 'Points to consider on clinical investigation of medicinal products other than NSAIDs (nonsteroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis' has provided guidance for the clinical development of both biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). In the last few years, several new products have been developed or are in development for the treatment of RA, which offer significant efficacy with regard to disease control, including prevention of structural damage and disability. Concurrently, novel insights have been gained with respect to the assessment of disease activity, joint damage and disability. New treatment strategies have been established which relate to early therapy, tight control and rapid switching of medication. Accordingly, several new EULAR/ACR recommendations have been or are being developed. Several important additions and changes are needed in the 2003 guidance to incorporate the current scientific knowledge into clinical trial design for the development of future products. Under the auspices of the Group for the Respect of Ethics and Excellence in Science (GREES), a group of experts in the field of RA and clinical trial design met to provide a consensus recommendation for an update to the 2003 EMA guidance document.

Research paper thumbnail of Clinical profile, contemporary management and one-year mortality in patients with severe acute heart failure syndromes: The EFICA study☆

European Journal of Heart Failure, 2006

Little is known about the epidemiology of acute decompensated heart failure (ADHF) in patients ad... more Little is known about the epidemiology of acute decompensated heart failure (ADHF) in patients admitted to intensive and coronary care units (ICU/CCU). Observational data may improve disease management and guide the design of clinical trials.

Research paper thumbnail of Recommendations for an update of 2003 European regulatory requirements for registration of drugs to be used in the treatment of RA

Current Medical Research and Opinion, 2011

Since 2003, the European Medicines Agency (EMA) document, &am... more Since 2003, the European Medicines Agency (EMA) document, 'Points to consider on clinical investigation of medicinal products other than NSAIDs (nonsteroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis' has provided guidance for the clinical development of both biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). In the last few years, several new products have been developed or are in development for the treatment of RA, which offer significant efficacy with regard to disease control, including prevention of structural damage and disability. Concurrently, novel insights have been gained with respect to the assessment of disease activity, joint damage and disability. New treatment strategies have been established which relate to early therapy, tight control and rapid switching of medication. Accordingly, several new EULAR/ACR recommendations have been or are being developed. Several important additions and changes are needed in the 2003 guidance to incorporate the current scientific knowledge into clinical trial design for the development of future products. Under the auspices of the Group for the Respect of Ethics and Excellence in Science (GREES), a group of experts in the field of RA and clinical trial design met to provide a consensus recommendation for an update to the 2003 EMA guidance document.

Research paper thumbnail of A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Safety and Efficacy of Etanercept 25 Twice Weekly in Patients with Severe Persistent Asthma

Research paper thumbnail of Variability in knee radiographing: implication for definition of radiological progression in medial knee osteoarthritis

Annals of the Rheumatic Diseases, 1998