Papers by Roberto Grimaldi
Vaccine, 2009
Background: Despite the established benefit of intramuscular (i.m.) influenza vaccination, new ad... more Background: Despite the established benefit of intramuscular (i.m.) influenza vaccination, new adjuvants and delivery methods for comparable or improved immunogenicity are being explored. Intradermal (i.d.) antigen administration is hypothesized to initiate an efficient immune response at reduced antigen doses similar to that observed after i.m. full dose vaccination. Methods: In a randomized, partially blinded phase II study 224, healthy adults aged ≥18 to ≤60 years were randomly assigned to four groups and received trivalent influenza vaccine at single doses of 3.0, 4.5 and 6.0 g hemagglutinin (HA) antigen of each influenza virus strain via i.d. injection or 15.0 g HA of each influenza strain via i.m. delivery. Serum anti-influenza virus antibodies were determined by hemagglutination inhibition (HI) assay before and 3 weeks after vaccination. Safety assessments were made at baseline and at the follow-up visit by the investigators and for a 4-day period post-vaccination by the subjects themselves. Results: The EMEA requirements for re-licensing of influenza vaccines were fulfilled in all groups 3 weeks after vaccination, irrespective of dose and mode of administration. High seroconversion rates were observed in all study groups and for all strains ranging from 50.9 to 85.5% and 70.4 to 87.0% after i.d. and i.m. vaccination, respectively. Seroprotection rates for the A strains A/Solomon Islands and A/Wisconsin were generally higher compared to the B/Malaysia strain and ranged from 89.1 to 98.2% across the i.d. groups. Similar rates of 96.3% for the A/Solomon Islands and 94.4% for the A/Wisconsin strain were observed in the i.m. group. Seroprotection rates for the B/Malaysia strain were 65.5, 83.0 and 72.7% after i.d. administration of 3.0, 4.5, and 6.0 g HA of each strain, respectively, compared to a seroprotection rate of 85.2% in the i.m. group. In addition, marked increases in geometric mean titer (GMT) were observed across the groups for all influenza virus strains ranging from 6.9 to 70.5 for i.d. and from 16.9 to 56.5 for i.m. antigen delivery. Both routes of administration were well tolerated. Systemic reactions were broadly similar across the groups. With respect to local reactions the frequency of injection site pain and ecchymosis were significantly lower following i.d. vaccination, while other local reactions such as erythema occurred at higher rates with i.d. than with i.m. vaccine administration, as expected due to the mechanism of action for the i.d. route. Conclusions: The virosomal adjuvanted influenza vaccine (Inflexal ® V) was shown to be overall highly immunogenic and well tolerated when given i.d. at reduced doses to healthy adults, eliciting an immune response similar to that observed with full dose i.m. administration and thus suggesting a promising antigen-sparing strategy for universal influenza vaccination against endemic influenza. Trial registration: ISRCTN registry number: 33950739.
Vaccine, 2008
Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cann... more Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cannot be provided due to limited availability of human or equine rabies immunoglobulin (HRIG and ERIG, respectively). We report first clinical data from two phase I studies evaluating a monoclonal antibody cocktail CL184 against rabies.
Vaccine, 2009
Background: Despite the established benefit of intramuscular (i.m.) influenza vaccination, new ad... more Background: Despite the established benefit of intramuscular (i.m.) influenza vaccination, new adjuvants and delivery methods for comparable or improved immunogenicity are being explored. Intradermal (i.d.) antigen administration is hypothesized to initiate an efficient immune response at reduced antigen doses similar to that observed after i.m. full dose vaccination. Methods: In a randomized, partially blinded phase II study 224, healthy adults aged ≥18 to ≤60 years were randomly assigned to four groups and received trivalent influenza vaccine at single doses of 3.0, 4.5 and 6.0 g hemagglutinin (HA) antigen of each influenza virus strain via i.d. injection or 15.0 g HA of each influenza strain via i.m. delivery. Serum anti-influenza virus antibodies were determined by hemagglutination inhibition (HI) assay before and 3 weeks after vaccination. Safety assessments were made at baseline and at the follow-up visit by the investigators and for a 4-day period post-vaccination by the subjects themselves. Results: The EMEA requirements for re-licensing of influenza vaccines were fulfilled in all groups 3 weeks after vaccination, irrespective of dose and mode of administration. High seroconversion rates were observed in all study groups and for all strains ranging from 50.9 to 85.5% and 70.4 to 87.0% after i.d. and i.m. vaccination, respectively. Seroprotection rates for the A strains A/Solomon Islands and A/Wisconsin were generally higher compared to the B/Malaysia strain and ranged from 89.1 to 98.2% across the i.d. groups. Similar rates of 96.3% for the A/Solomon Islands and 94.4% for the A/Wisconsin strain were observed in the i.m. group. Seroprotection rates for the B/Malaysia strain were 65.5, 83.0 and 72.7% after i.d. administration of 3.0, 4.5, and 6.0 g HA of each strain, respectively, compared to a seroprotection rate of 85.2% in the i.m. group. In addition, marked increases in geometric mean titer (GMT) were observed across the groups for all influenza virus strains ranging from 6.9 to 70.5 for i.d. and from 16.9 to 56.5 for i.m. antigen delivery. Both routes of administration were well tolerated. Systemic reactions were broadly similar across the groups. With respect to local reactions the frequency of injection site pain and ecchymosis were significantly lower following i.d. vaccination, while other local reactions such as erythema occurred at higher rates with i.d. than with i.m. vaccine administration, as expected due to the mechanism of action for the i.d. route. Conclusions: The virosomal adjuvanted influenza vaccine (Inflexal ® V) was shown to be overall highly immunogenic and well tolerated when given i.d. at reduced doses to healthy adults, eliciting an immune response similar to that observed with full dose i.m. administration and thus suggesting a promising antigen-sparing strategy for universal influenza vaccination against endemic influenza. Trial registration: ISRCTN registry number: 33950739.
Vaccine, 2008
Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cann... more Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cannot be provided due to limited availability of human or equine rabies immunoglobulin (HRIG and ERIG, respectively). We report first clinical data from two phase I studies evaluating a monoclonal antibody cocktail CL184 against rabies.
Angiology, 1990
The variation of capillary filtration rate (CFR), ankle circumference (AC), and ankle edema (AE) ... more The variation of capillary filtration rate (CFR), ankle circumference (AC), and ankle edema (AE) was evaluated in three groups of patients with venous hypertension (ambulatory venous pressure greater than 42 mmHg) and in a group of normal subjects before and after treatment for four weeks with Total Triterpenic fraction of Centella Asiatica (TTFCA), a venoactive drug acting on the microcirculation and on capillary permeability. Group A (20 patients) was treated with TTFCA 60 mg tid; Group B (20 patients) was treated with 30 mg tid; Group C (12 patients) was treated with placebo; and Group D (10 normal subjects) was treated with TTFCA 60 mg tid in an open study. Capillary filtration rate was assessed by venous occlusion plethysmography, ankle edema by a new system called AECT (Ankle edema coin tester). Subjective symptoms of venous hypertension were assessed by an analogue scale line considering four symptoms: swelling sensation, restless lower extremity, pain and cramps, and tiredness. CFR, AC, and AE were significantly higher in patients in comparison with normal subjects. After four weeks of TTFCA treatment there was a significant decrease of the abnormally increased CFR, AC, and AECT time in patients. This was also greater in the higher dose group. No significant change was observed in the placebo group and in normal subjects treated with TTFCA. Symptoms were also significantly improved in the two groups treated with the active drug according to the dose. No significant changes were observed in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiology, 1990
The VSC (vacuum suction chamber) device, a new system to evaluate local capillary permeability, w... more The VSC (vacuum suction chamber) device, a new system to evaluate local capillary permeability, was used with laser Doppler flowmetry to study variations of permeability and of the microcirculation in 10 normal subjects; in 22 patients with moderate, superficial venous hypertension; and in 12 patients with postphlebitic limbs and severe venous hypertension. All these patients had distal (ankle and foot edema) in the evening. After a first assessment these subjects were studied again after two weeks without treatment and after two weeks' treatment with total triterpenic fraction of centella asiatica (TTFCA), tablets, 60 mg, tid. The VSC produces a wheal on the skin of the perimalleolar region that disappears (in average) in less than sixty minutes in normal subjects. The disappearance time (DT) is greater in conditions of increased capillary filtration and permeability. The three groups of subjects (normal and those with superficial and severe venous hypertension) had significantly different, increasing disappearance time of the wheals at the first observation. There were no significant changes after two weeks' observation, but after 2 weeks' treatment with TTFCA, there was a significant decrease of DT both in limbs with superficial and with deep venous incompetence. The improvement (decrease) of the abnormally increased capillary permeability was associated with a significant improvement of the microcirculation and symptoms (studied by an analogue scale line). In conclusion this study showed a combined improvement of the microcirculation and capillary permeability after treatment with TTFCA and the possibility of using the VSC to evaluate the effects of drugs (or other treatment) on local capillary permeability in patients with venous hypertension.
Angiology, 1990
The variation of capillary filtration rate (CFR), ankle circumference (AC), and ankle edema (AE) ... more The variation of capillary filtration rate (CFR), ankle circumference (AC), and ankle edema (AE) was evaluated in three groups of patients with venous hypertension (ambulatory venous pressure greater than 42 mmHg) and in a group of normal subjects before and after treatment for four weeks with Total Triterpenic fraction of Centella Asiatica (TTFCA), a venoactive drug acting on the microcirculation and on capillary permeability. Group A (20 patients) was treated with TTFCA 60 mg tid; Group B (20 patients) was treated with 30 mg tid; Group C (12 patients) was treated with placebo; and Group D (10 normal subjects) was treated with TTFCA 60 mg tid in an open study. Capillary filtration rate was assessed by venous occlusion plethysmography, ankle edema by a new system called AECT (Ankle edema coin tester). Subjective symptoms of venous hypertension were assessed by an analogue scale line considering four symptoms: swelling sensation, restless lower extremity, pain and cramps, and tiredness. CFR, AC, and AE were significantly higher in patients in comparison with normal subjects. After four weeks of TTFCA treatment there was a significant decrease of the abnormally increased CFR, AC, and AECT time in patients. This was also greater in the higher dose group. No significant change was observed in the placebo group and in normal subjects treated with TTFCA. Symptoms were also significantly improved in the two groups treated with the active drug according to the dose. No significant changes were observed in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiology, 1990
The VSC (vacuum suction chamber) device, a new system to evaluate local capillary permeability, w... more The VSC (vacuum suction chamber) device, a new system to evaluate local capillary permeability, was used with laser Doppler flowmetry to study variations of permeability and of the microcirculation in 10 normal subjects; in 22 patients with moderate, superficial venous hypertension; and in 12 patients with postphlebitic limbs and severe venous hypertension. All these patients had distal (ankle and foot edema) in the evening. After a first assessment these subjects were studied again after two weeks without treatment and after two weeks' treatment with total triterpenic fraction of centella asiatica (TTFCA), tablets, 60 mg, tid. The VSC produces a wheal on the skin of the perimalleolar region that disappears (in average) in less than sixty minutes in normal subjects. The disappearance time (DT) is greater in conditions of increased capillary filtration and permeability. The three groups of subjects (normal and those with superficial and severe venous hypertension) had significantly different, increasing disappearance time of the wheals at the first observation. There were no significant changes after two weeks' observation, but after 2 weeks' treatment with TTFCA, there was a significant decrease of DT both in limbs with superficial and with deep venous incompetence. The improvement (decrease) of the abnormally increased capillary permeability was associated with a significant improvement of the microcirculation and symptoms (studied by an analogue scale line). In conclusion this study showed a combined improvement of the microcirculation and capillary permeability after treatment with TTFCA and the possibility of using the VSC to evaluate the effects of drugs (or other treatment) on local capillary permeability in patients with venous hypertension.
Pain, 2011
Spinal cord stimulation (SCS) is believed to be effective in treating refractory angina. The need... more Spinal cord stimulation (SCS) is believed to be effective in treating refractory angina. The need for SCSrelated chest paresthesia, however, has hitherto made impossible placebo-controlled trials. Subliminal (non paresthesic) SCS, however, might be also effective on anginal pain. In this trial we compared subliminal SCS with paresthesic SCS and with sham SCS. Twenty-five refractory angina patients, who had never received SCS before, underwent SCS device implantation and were randomized to three groups: paresthesic SCS (group PS; n = 10), subliminal SCS (group SS; n = 7) or ''sham" SCS (group NS; n = 8). After 1 month group NS patients were randomized to either group PS or SS. After 1 month, changes in angina episodes (p = 0.016), nitroglycerin use (p = 0.015), angina class (p = 0.02), quality of life score (p = 0.05), and items 2 (p = 0.008) and 3 (p = 0.009) of Seattle angina questionnaire differed significantly among groups. Group PS showed significant improvement in outcomes compared to group NS, whereas there were no significant differences between groups SS and NS; furthermore, only nitroglycerin use differed significantly between groups PS and SS. At 3 months, a significant difference between groups PS and SS was observed in angina attacks (p = 0.002), but not in other variables. Thus, in this study, paresthesic, but not subliminal SCS was superior to sham SCS in improving clinical status in refractory angina patients. The lack of significant differences between PS and SS groups in this small study suggests that a possible role for subliminal SCS in individual patients deserves to be assessed in larger trials with appropriate statistical power.
Pace-pacing and Clinical Electrophysiology, 2009
Background: Spinal cord stimulation (SCS) has proven antianginal and antiischemic effects in seve... more Background: Spinal cord stimulation (SCS) has proven antianginal and antiischemic effects in severe coronary artery disease patients, minimizing frequency, intensity, and duration of pain. The mechanism explaining these effects has been detected in a sympathicolytic effect of the SCS. We monitored 30minute-long recordings of the heart rate variability (HRV) and its spectral power parameters to evaluate the influence of SCS on the sympathetic/parasympathetic balance.
Journal of Cardiovascular Medicine, 2015
A 29-year-old woman with two mechanical valve prostheses was referred to our institution for sudd... more A 29-year-old woman with two mechanical valve prostheses was referred to our institution for sudden and self-resolved diplopia 2 weeks after childbirth. From the beginning of pregnancy, nadroparin was started instead of warfarin. The echocardiogram performed at hospital admission revealed a severe aortic prosthesis regurgitation due to incomplete leaflet apposition with a prosthetic aortic transvalvular gradient increase. Three-dimensional transoesophageal echocardiography revealed a thrombus located between the two prostheses, causing intermittent aortic valve malfunction. Intravenous heparin was started. Three days later, a second transoesophageal echocardiogram revealed a decreased aortic transvalvular gradient, but an oval thrombus adhered to the mitral prosthesis and fluctuating through the prosthetic valve was detected. Tissue plasminogen activator infusion was started. To reduce cerebral embolization, carotid filters used during artery angioplasty were placed in common carotid arteries, left and right. No complication occurred during and after the procedure. With thrombus absence at 30-min transoesophageal echocardiography, filters were removed. The patient continued intravenous heparin until achievement of a therapeutic international normalized ratio range and she was asymptomatic on discharge.
Journal of The American College of Cardiology, 2002
Aims An antiarrhythmic effect of spinal cord stimulation (SCS) has been recognized in an animal m... more Aims An antiarrhythmic effect of spinal cord stimulation (SCS) has been recognized in an animal model. The actual mechanism is still mainly unknown. An adrenergic output reduction has been advocated as the main mechanism, although a modulation effect on the arrhythmic substrate has not yet been investigated. We studied T-wave alternans (TWA) modifications to test the hypothesis that SCS affects the arrhythmic substrate.
Pace-pacing and Clinical Electrophysiology, 2007
Wiley also publishes its books in a variety of electronic formats. Some content that appears in p... more Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment by physicians for any particular patient. The publisher and the authors make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. Readers should consult with a specialist where appropriate. The fact that an organization or website is referred to in this work as a citation and/or a potential source of further information does not mean that the authors or the publisher endorse the information the organization or website may provide or recommendations it may make. Further, readers should be aware that internet websites listed in this work may have changed or disappeared between when this work was written and when it is read. No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom.
European Journal of Clinical Pharmacology, 1986
The kinetics of phenobarbital (PB) was compared after oral administration of equivalent doses of ... more The kinetics of phenobarbital (PB) was compared after oral administration of equivalent doses of the drug as the acid or the propylhexedrine salt (barbexaclone) to 7 normal volunteers. The absorption and elimination parameters were very similar. It was concluded that propylhexedrine did not affect the serum kinetics of PB given as barbexaclone.
Pharmacopsychiatry, 1987
The pharmacodynamic and kinetic profiles of two oral biperiden formulations (tablet with instant-... more The pharmacodynamic and kinetic profiles of two oral biperiden formulations (tablet with instant-release and sugar-coated tablet with slow-release) were studied in a total of 12 healthy subjects after the administration of a 4 mg dose and compared in part to placebo. Biperiden as slow-release formulation showed much slower absorption than the instant-release tablet; whereas plasma levels peaked as early as 1-2 h after administration of the tablet, with the slow-release formulation a first peak was seen approximately 4.5 h after intake in the majority of the subjects. In some subjects this was followed by a trough, in others by formation of a shoulder at around 0.5 ng/ml. In all subjects a peak of about 1.0 ng/ml was reached after 10-12 h. The instant-release tablet and the slow-release formulation showed comparable bioavailability. Plasma concentrations for the slow-release formulation at 24 h were around 0.5 ng/ml, about twice as high as those for the instant-release formulation. The ratio of peak to 24 h values showed the marked reduction which is characteristic for a slow-release formulation compared with the instant-release tablet. The subjective well-being of the volunteers was not influenced by the slow-release formulation, whereas after the instant-release tablet slight CNS effects (dizziness, drowsiness and fatigue) were reported up to 6 h after ingestion. Furthermore, objectively quantifiable pharmacodynamic ocular parameters (near-point accomodation, pupil size) and the secretion of saliva proved to be less affected by the slow-release formulation than by the instant-release tablet, or not affected at all.
European Journal of Clinical Pharmacology, 1986
The medicinal herb formulation Da-Cheng-Qi decoction (DCQD) has been shown to ameliorate the seve... more The medicinal herb formulation Da-Cheng-Qi decoction (DCQD) has been shown to ameliorate the severity of acute pancreatitis by regulating an apoptosis-necrosis switch in cells. The active components responsible for this effect and their detailed mechanism of action remain unclear. Here we determine the pharmacokinetic characteristics of the four most abundant compounds in DCQD using a rat model of severe acute pancreatitis. Acute pancreatitis-like symptoms were first induced in rats and then they were given DCQD orally. Rhein was found in rat serum at much higher levels than magnolol, hesperidin, or naringin, even though it was the least abundant of the four compounds in the DCQD. We also examined pharmacodynamics in AR42J cells stimulated with 10(-8) M cerulein as a cellular model of acute pancreatitis. After pretreating AR42J cells with individual compounds and then exposing them to cerulein, we determined cell viability, levels of apoptosis and necrosis, and numbers of cells positive for reactive oxygen species (ROS). Pretreatment with any of the four DCQD compounds increased cell viability and the apoptosis index, while also reducing necrosis and ROS generation. The compounds showed maximal effect in AR42J cells around the same time that they showed maximum serum concentration in rats. Although all four components appear to play a role in an apoptosis-necrosis cellular switch in vitro, rhein may be the most bioactive DCQD ingredient.
Journal of Ethnopharmacology, 1986
Various tests of psychomotor performance were carried out in a group of 16 healthy male volunteer... more Various tests of psychomotor performance were carried out in a group of 16 healthy male volunteers given a standardized preparation of Korean ginseng (G 115; 100 mg twice a day for 12 weeks) and in a similar group given identical placebo capsules under double-blind conditions. A favourable effect of G 115 relative to baseline performance was observed in attention (cancellation test), processing (mental arithmetic, logical deduction), integrated sensory-motor function (choice reaction time) and auditory reaction time. However, end performance of the G 115 group was superior statistically to the placebo group only in mental arithmetic. No difference between G 115 and placebo was found in tests of pure motor function (tapping test),, recognition (digit symbol substitution) and visual reaction time. No adverse effects were reported. It is concluded that G 115 may be superior to placebo in improving certain psychomotor functions in healthy subjects.
Journal of Ethnopharmacology, 1990
... The Italian Journal of Biochemistry 37 (1988), pp. 6977. View Record in Scopus | Cited By in... more ... The Italian Journal of Biochemistry 37 (1988), pp. 6977. View Record in Scopus | Cited By in Scopus (23). Corresponding Author Contact Information Correspondence to: Dr. F. De Ponti. Copyright © 1990 Published by Elsevier Ireland Ltd. Journal of Ethnopharmacology ...
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Papers by Roberto Grimaldi