Patient involvement in pharmacovigilance: determinants and evolution of reporting from 2011 to 2020 in France.

INTRODUCTION: Because patients and patient organizations want to strengthen their role in the care pathway and drug evaluation and in order to improve pharmacovigilance activities, European competent authorities implemented regulations to allow direct reporting of adverse drug reactions related to medicinal products by patients in 2012. OBJECTIVES: To describe evolution and analyze determinants of patient reporting activity in France in order to assess patient involvement in pharmacovigilance. METHOD: Using the French national pharmacovigilance database, univariate and multivariate analyses were performed to compare the characteristics of adverse drug reaction (ADR) reports from patients and healthcare professionals (HCP) between 2011 and 2020. The relationship between regional patient ADR report activity and regional care provision and socio-professional characteristics was analyzed using the principal component analysis. RESULTS: A significant and higher increase in ADR reports over time from patients (r = 0.89, p < 0.001) compared to HCP (r = 0.27, p = 0.002) has been observed. Patient ADR report activities compared to HCP concerned more women (80% vs. 55%, p < 0.001), younger age classes (p < 0.001), reporting through web portal (83% vs. 17%, p < 0.001), and less serious events (26% vs. 63%, p < 0.001). In the principal component analysis, regional patient reporting activity was related to socio-professional categories, age classes, and densities of hospital beds and physicians. CONCLUSION: Our results confirm an increasing involvement of patients in ADR report activities. The determinants of patient reporting activities are not only related to drug and medical factors but also to social factors. Digital tools may also play a role in health democracy in pharmacovigilance.

Allergy in adolescent population (14-18 years) living in Campania region (Southern Italy). A multicenter study.

Summary: Adolescents (Ad) constitute a difficult to manage population among individuals suffering from asthma. The aim of our study was to assess the prevalence, clinical characteristics and age of onset of allergic sensitization and clinical symptoms in a sample of atopic Ad living in the Campania region (Southern Italy). Sixteen Allergy units or Centers belonging to the Italian Association of Hospital and Territorial Allergologists (AAIITO, Campania region) participated in this cross-sectional study. A case report form (CRF) was specifically designed for this study and commercial allergen extracts used for screening SPTs were provided by ALK-Abelló Group (Milan, Italy). A total of 443 patients were examined (females, f 220, 49.6 %; males, m 223, 50.3%). Dust mites represent the most common sensitizing agents in allergic Ad living in Campania region (Dermatoph. pteronyssinus 67.4% and Dermatoph. farinae 66.5%), followed by Parietaria (58.9%), grasses (45.8%), Artemisia vulgaris (16.7%), Olea Europaea (32.2%), dog dander (17.1%), cat dander (20.0%), Alternaria alternata (8.1%), Cupressus sempervirens (4.9%), Betula pendula (4.7%), other allergens (19.4%). An interesting comparison has been made between clinical data of our Ad with data of elderly patients (E). The role of allergic sensitization is significantly higher in Ad compared to E. Dermatophagoides pteronyssinus is the first sensitizing allergen in Ad and the last in E. Parietaria constitutes the first sensitizing pollen both in Ad and E, the percentage of sensitization is higher in Ad. Another important difference is the higher prevalence of As, as only symptom, in E compared to Ad (19.7% versus 7.6%). In conclusion, our findings confirm the high prevalence and clinical significance of airway allergic sensitization in the adolescents living in Campania region.

Strong Reduction of the Effective Radiation Length in an Axially Oriented Scintillator Crystal.

We measured a considerable increase of the emitted radiation by 120 GeV/c electrons in an axially oriented lead tungstate scintillator crystal, if compared to the case in which the sample was not aligned with the beam direction. This enhancement resulted from the interaction of particles with the strong crystalline electromagnetic field. The data collected at the external lines of the CERN Super Proton Synchrotron were critically compared to Monte Carlo simulations based on the Baier-Katkov quasiclassical method, highlighting a reduction of the scintillator radiation length by a factor of 5 in the case of beam alignment with the [001] crystal axes. The observed effect opens the way to the realization of compact electromagnetic calorimeters or detectors based on oriented scintillator crystals in which the amount of material can be strongly reduced with respect to the state of the art. These devices could have relevant applications in fixed-target experiments, as well as in satellite-borne γ telescopes.

Allergic sensitization to common pets (cats/dogs) according to different possible modalities of exposure: an Italian Multicenter Study.

BACKGROUND: The query "are there animals at home?" is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. METHODS: Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. RESULTS: A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150-20.75%) or indirect contact (103-14.25%), in 111 subjects (15.35%) any contact was reported. CONCLUSIONS: Only 213 patients (29.46%) would be classified as "exposed to animals" and 510 (70.54%) as "not exposed" according to usual query. Our classification has shown that many "not-exposed" subjects (399-55.19%) were "really exposed". The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals.

Allergy in urban elderly population living in Campania region (Southern Italy). A multicenter study.

Given the increasing life expectancy observed in Western countries, there is a marked interest to know more about how aging could influence respiratory health. The aim of our study was to assess the prevalence, clinical characteristics and age of onset of allergic sensitization and clinical symptoms in a sample of atopic elders living in Campania region area (Southern Italy). Fourteen Allergy units or Centres examined a total of 462 patients. In this context 215 (46.53%) had positive skin prick tests (SPTs) to at least one allergen and were diagnosed with respiratory allergy. Parietaria represents the most common sensitizing agent in elders living in Campania region, followed by dust mites, grass pollen and Olea europaea. A relatively high percentage of atopic subjects suffered from respiratory symptoms at a fairly advanced age, namely 8.3% at 60-64 years, 10.2% at 65-70 and 5.7% at > 70 years. In conclusion, the prevalence and clinical significance of airway allergic sensitization in the elderly living in Campania region is more significant than expected in latter stages of life. Physicians should not neglect the role of atopy as a risk factor for the onset of allergic respiratory symptoms even in elderly patients.

Investigation of the Electromagnetic Radiation Emitted by Sub-GeV Electrons in a Bent Crystal.

The radiation emitted by 855 MeV electrons via planar channeling and volume reflection in a 30.5-µm-thick bent Si crystal has been investigated at the MAMI (Mainzer Mikrotron) accelerator. The spectral intensity was much more intense than for an equivalent amorphous material, and peaked in the MeV range in the case of channeling radiation. Differently from a straight crystal, also for an incidence angle larger than the Lindhard angle, the spectral intensity remains nearly as high as for channeling. This is due to volume reflection, for which the intensity remains high at a large incidence angle over the whole angular acceptance, which is equal to the bending angle of the crystal. Monte Carlo simulations demonstrated that incoherent scattering significantly influences both the radiation spectrum and intensity, either for channeling or volume reflection. In the latter case, it has been shown that incoherent scattering increases the radiation intensity due to the contribution of volume-captured particles. As a consequence, the experimental spectrum becomes a mixture of channeling and pure volume reflection radiations. These results allow a better understanding of the radiation emitted by electrons subjected to coherent interactions in bent crystals within a still-unexplored energy range, which is relevant for possible applications for innovative and compact x-ray or γ-ray sources.

Orientational Coherent Effects of High-Energy Particles in a LiNbO3 Crystal.

A bent lithium niobate strip was exposed to a 400-GeV/c proton beam at the external lines of CERN Super Proton Synchrotron to probe its capabilities versus coherent interactions of the particles with the crystal such as channeling and volume reflection. Lithium niobate (LiNbO3) exhibits an interplanar electric field comparable to that of Silicon (Si) and remarkable piezoelectric properties, which could be exploited for the realization of piezo-actuated devices for the control of high-energy particle beams. In contrast to Si and germanium (Ge), LiNbO3 shows an intriguing effect; in spite of a low channeling efficiency (3%), the volume reflection maintains a high deflection efficiency (83%). Such discrepancy was ascribed to the high concentration (10(4) per cm2) of dislocations in our sample, which was obtained from a commercial wafer. Indeed, it has been theoretically shown that a channeling efficiency comparable with that of Si or Ge would be attained with a crystal at low defect concentration (less than ten per cm2). To better understand the role of dislocations on volume reflection, we have worked out computer simulation via dynecharm++ Monte Carlo code to study the effect of dislocations on volume reflection. The results of the simulations agree with experimental records, demonstrating that volume reflection is more robust than channeling in the presence of dislocations.

Steering of a sub-GeV electron beam through planar channeling enhanced by rechanneling.

We report the observation of efficient steering of a 855 MeV electron beam at MAMI (MAinzer MIkrotron) facilities by means of planar channeling and volume reflection in a bent silicon crystal. A 30.5 µm thick plate of (211) oriented Si was bent to cause quasimosaic deformation of the (111) crystallographic planes, which were used for coherent interaction with the electron beam. The experimental results are analogous to those recorded some years ago at energy higher than 100 GeV, which is the only comparable study to date. Monte Carlo simulations demonstrated that rechanneling plays a considerable role in a particle's dynamics and hinders the spoiling of channeled particles. These results allow a better understanding of the dynamics of electrons subject to coherent interactions in a bent silicon crystal in the sub-GeV energy range, which is relevant for realization of innovative x-ray sources based on channeling in periodically bent crystals.

Coherent effects of high-energy particles in a graded Si(1-x)Ge(x) crystal.

A graded Si(1-x)Ge(x) crystal has been manufactured for operation with high-energy protons to excite coherent interactions of the particles with the crystal such as channeling and volume reflection. The crystal had the shape of a parallelepiped though its (111) atomic planes were curved at a radius of 25.6 m because of the graded Ge content. The crystal was exposed to a 400 GeV/c proton beam at the external lines of CERN Super Proton Synchrotron to probe its capability to steer high-energy particles. Measured deflection efficiency was 62.0% under planar channeling and 96.0% under volume reflection. Such values are critically compared to their counterparts for a standard bent Si crystal under peer conditions. A Monte Carlo simulation of the dynamics of channeled and volume reflected particles in a graded crystal including the effect of Ge impurities and of lattice dislocations has been carried out. We found that the effect of crystal imperfections spoiled the efficiency of channeling while it negligibly affected the performance of volume reflection. We finally propose the usage of the graded crystal as a primary scatterer to aid halo collimation for the new generation of hadronic machines. As a unique feature, a properly cut graded crystal circumvents the problem of the miscut angle, which is currently a severe limitation for implementation of crystal-assisted collimation.

Broad and intense radiation accompanying multiple volume reflection of ultrarelativistic electrons in a bent crystal.

The radiation emitted by 120 GeV/c electrons traversing a single bent crystal under multiple volume reflection orientation is investigated. Multiple volume reflection in one crystal occurs as a charged particle impacts on a bent crystal at several axial channeling angles with respect to a crystal axis. The resulting energy-loss spectrum of electrons was very intense over the full energy range up to the nominal energy of the beam. As compared to the radiation emission by an individual volume reflection, the energy-loss spectrum is more intense and peaks at an energy 3 times greater. Experimental results are compared to a theoretical approach based on the direct integration of the quasiclassical Baier and Katkov formula. In this way, it is possible to determine the mean number of photons emitted by each electron and, thus, to extract the single-photon spectrum, which is broad and intense. The soft part of the radiation spectrum is due to the contribution of coherent interaction between electrons and several reflecting planes intersecting the same crystal axis, whereas the hard part is mainly connected to coherent bremsstrahlung induced by correlated scattering of electrons by atomic strings (string of strings scattering and radiation). The radiation generation by multiple volume reflection takes place over a broad angular range of the incident beam with respect to coherent bremsstrahlung and channeling radiation in straight crystals. Therefore, this type of radiation can be exploited for applications, such as beam dump and collimation devices for future linear colliders.

[Latency: relevant element in the attribution, forecast, and prevention of occupational neoplasms]. / La latenza: elemento rilevante nella attribuzione, previsione e prevenzione delle neoplasie professionali.

The knowledge on latencies of occupational cancers is relevant as far as causal diagnosis, epidemiologic forecast and primary and secondary prevention are concerned. Literature mainly shows highly non specific data on tumour latencies. The widest burden of available data on occupational cancers relates to mesothelioma due to asbestos exposure. Data covering different cancers are scanty. The present review of available data anyway allows to set some values that can serve as a reference, even though major limitations are to be considered. In particular, still unanswered questions deal with the leading role of either the cancerogenic power of agents, or of the dose, the organ susceptibility, the cell doubling time of specific neoplasms, the role of confundings. Due to the high dispersion of the latency values reported for single tumour types, it is still questionable if mean or median values can be deemed reliable.

Sensitization to horse allergens in Italy: a multicentre study in urban atopic subjects without occupational exposure.

BACKGROUND: Horses play a significant role in people's leisure time in Italy and other countries, but few data are available on IgE-mediated sensitization to horse allergens in patients without occupational exposure. We assessed, in a multicentric survey, the prevalence of horse sensitization in atopic subjects and its clinical characteristics. METHODS: Allergists from the whole Italian territory were required to collect the results of skin prick tests from at least 100 consecutive subjects. Those patients with a positive skin test to horse dander underwent a detailed interview concerning clinical history, pet ownership and possible exposure. RESULTS: Data from 3,235 outpatients were collected and 2,097 had at least 1 skin positivity. Among them, 113 (5.38%) were sensitized to horse dander (9 monosensitized). Thirty patients reported direct horse contact (4 owners and 26 for riding or occasional contact), 23 patients were sometimes in contact with horse owners and 60 subjects denied any direct or indirect exposure. Among 9 horse monosensitized patients, 6 had intermittent and mild rhinitis and 3 persistent moderate/severe rhinitis plus asthma. Three of them were horse owners or riders and the remaining had no contact with the animal. CONCLUSIONS: Our data evidence that the rate of sensitization to horse dander is not negligible and probably underestimated. In susceptible, not occupationally exposed individuals, horse contact, but also indirect or no apparent exposure, may induce sensitization. We recommend inclusion of horse allergen in the routine panel for the diagnosis of respiratory allergy.

[Criteria to notify to the authorities the occupational lumbar trait diseases]. / Criteri per la denuncia ex D.M. 27/4/04 delle spondilodiscopatie del tratto lombare e dell'ernia discale lombare.

To carry out the requirement of notification according to the Italian law D.M. 27/4/04 in relation to the item "Manual handling of loads made continuously during working shift" it is necessary to clarify some quantitative and chronological aspects regarding the exposure and to precise the nature of the diseases to be notified. To fulfil their choices doctors at the moment can not rely on quantitative referrings based on the evidence and wide spread accepted, but they basically have operative indications partly taken from literature and stil under validation. However, to carry out the requirement of the law and to avoid choices not based on considered criteria, we propose some operative criteria deriving from the knowledge that at the moment seems more consolidated and accepted in the occupational and previdential medicine.

Air particulate matter exacerbates lung response on Sjögren's Syndrome animals.

Epidemiological studies have associated air particulate matter (PM) inhalation with a decline in lung function and increased morbo-mortality due to cardiorespiratory diseases, particularly in susceptible populations. Sjögren's Syndrome (SS) is a chronic autoimmune disease characterized by cellular infiltration in exocrine glands and extraglandular tissue, being the respiratory tract an important target. We evaluated the effect of PM on the airways of NOD mice, which develop SS and BALB/c mice. BALB/c or NOD mice (2-3 months) were randomized in two groups and exposed to intranasal instillation either with saline (control) or ROFA solution (1mg/kg body weight). After 24h, mice were euthanized in order to perform lung histology, or measure total cell number (TCN), differential cell count (DCC) and superoxide anion generation in the bronchoalveolar lavage (BAL) fluid. BALB/c mice showed normal histoarchitecture, while NOD mice showed lymphocytic peribronchial infiltrates. ROFA exposure affected the respiratory tract from both BALB/c and NOD mice, with a significant increase in the TCN (p<0.05) and generation of O2(-) (p<0.05), as well as an imbalance in the DCC (p<0.05). All histological observations correlated with the cellular parameters evaluated. Lesions in NOD mice were more severe than those of BALB/c, showing cellular infiltration in the alveoli and leading to a greater decrease in the alveolar space. We have proved that in this experimental Sjögren's Syndrome animal model (NOD mice); airborne pollution exacerbates pre-existing pulmonary lesions. These findings show experimental evidence on the harmful effects of airborne pollution on the airways of patients with Sjögren's Syndrome.

The experimental setup of the Interaction in Crystals for Emission of RADiation collaboration at Mainzer Mikrotron: Design, commissioning, and tests.

Silicon/germanium flat/bent crystals are thin devices able to efficiently deflect charged particle GeV-energy beams up to a few hundreds of µrad; moreover, high intensity photons can be efficiently produced in the so-called Multi-Volume Reflection (MVR) and Multiple Volume Reflections in One Crystal (MVROC) conditions. In the last years, the research interest in this field has moved to the dynamic studies of light negative leptons in the low energy range: the possibility to deflect negative particles and to produce high intensity γ sources via the coherent interactions with crystals in the sub-GeV energy range has been proved by the ICE-RAD (Interaction in Crystals for Emission of RADiation) Collaboration at the MAinzer MIkrotron (MAMI, Germany). This paper describes the setup used by the ICE-RAD experiment for the crystals characterization (both in terms of deflection and radiation emission properties): a high precision goniometer is used to align the crystals with the incoming beam, while a silicon based profilometer and an inorganic scintillator reconstruct, respectively, the particle position and the photon spectra after the samples. The crystals manufacturing process and their characterization, the silicon profilometer commissioning at the CERN PS T9 beamline, and the commissioning of the whole setup installed at MAMI are presented.

Tuberculosis incidence in developing countries with high prevalence of HIV infection.

OBJECTIVE: To study the impact of the HIV epidemic on tuberculosis (TB) incidence in developing countries. DESIGN: A simple mathematical model is constructed using figures from published reports to estimate the rise of TB incidence as the HIV epidemic expands. METHOD: Two groups with different risk of developing TB are identified: individuals with dual infection of HIV and Mycobacterium tuberculosis and the rest of the population. The model is based on a combination of the incidence and the percentage of TB in these two groups. The expected rise in TB incidence and the percentage of TB cases that will be HIV-positive are plotted against the prevalence of HIV. CONCLUSIONS: Unless appropriate action is taken, TB incidence in developing countries will double as the prevalence of HIV infection reaches 13 per hundred adults.

PIP: 95% of tuberculosis (TB) cases in the world live in developing countries. HIV infection greatly increases the risk of developing active TB among those with latent Mycobacterium tuberculosis infection. Thus researchers have used data from existing research to develop a mathematical model to gauge the increase in TB incidence in developing countries while considering rising HIV prevalence among adults. They look at 2 groups with sizable differences in risk of acquiring TB: adults with both HIV and M. tuberculosis infections and all other adults. The researchers plot the expected increase in TB incidence and percentage of TB cases that also have HIV infection against HIV prevalence. According to the model, when the prevalence of HIV infection hits 13% of adults in developing countries, the number of new TB cases doubles. Most of this increase will occur in areas that already lack diagnostic services, drugs, hospital beds, and other needed supplies. TB chemoprophylaxis treatment of HIV-positive people could result in a lower increase in TB incidence, however. WHO has set a goal of 50% reduction in TB incidence by 2002. Public health officials could use this model to plan TB control programs to bring about a reduction in the increase. Even though TB control programs can help stem the projected increase, it will be very difficult for developing countries with high HIV prevalence to hold back the projected rise in TB incidence. Developing countries must take considerable appropriate action soon to prevent doubling of TB incidence as HIV prevalence nears 13% of adults.

Muscarinic acetylcholine receptor antibodies as a new marker of dry eye Sjögren syndrome.

PURPOSE: The authors investigated whether circulating autoantibodies against M(3) muscarinic acetylcholine receptors (mAChRs) could be a new marker for diagnosis for primary and secondary Sjögren syndrome (SS) dry eye. METHODS: Enzyme-linked immunosorbent assay (ELISA) using both rat exorbital lacrimal gland acinar cell membranes and synthetic 25-mer peptide as antigens was used to determine autoantibodies against acinar cells and M(3) mAChRs. Also, nitric oxide synthase (NOS) activity was assessed to determine the biological effect of these autoantibodies in relation to the M(3) mAChR. RESULTS: Sera from dry eye primary SS (pSS) or secondary SS (sSS) patients tested by ELISA recognized membrane lacrimal gland acinar cells antigens and the synthetic 25-mer peptide, corresponding to the second extracellular loop of human M(3) mAChRs. Moreover, the IgG fraction and the corresponding affinity-purified anti-M(3) peptide autoantibodies from the same patients were able to activate NOS coupled to lacrimal gland M(3) mAChRs. As controls, IgG and sera from women without dry eye with or without rheumatoid arthritis and from normal control subjects gave negative results on ELISA and biological assay; thus demonstrating the specificity of the reaction. CONCLUSIONS: Autoantibodies against mAChR may be considered among the serum factors implicated in the pathophysiology of the development of pSS dry eyes and could be a new marker to differentiate SS dry eyes from non-SS dry eyes.

Heat shock protein expression in human conjunctiva.

PURPOSE: To examine the distribution of human heat shock proteins (HSPs) HSP90, inducible HSP70 (iHSP70), constitutive and inducible HSP70 (cHSP70), HSP65, and human HSP27 in conjunctival biopsy specimens of ocular cicatricial pemphigoid (OCP), atopic keratoconjunctivitis, and healthy persons with cataract. METHODS: Using an immunoperoxidase technique, conjunctival biopsy specimens from ten patients with ocular cicatricial pemphigoid, ten patients with atopic keratoconjunctivitis and ten healthy persons undergoing cataract surgery were analyzed with a panel of monoclonal antibodies directed against human HSPs. RESULTS: Large amounts of HSP90 and HSP27, and lesser amounts of cHSP70, iHSP70, and HSP65 were present in atopic keratoconjunctivitis and normal epithelium; less of these proteins were seen in OCP conjunctival epithelium. In atopic keratoconjunctivitis and normal tissue the substantia propria contained a few HSP-positive cells, and the vascular endothelium was consistently negative for all of the HSPs. In sharp contrast, OCP stroma contained large numbers of cells staining for HSP27, HSP90, and iHSP70, and the vasculature was strongly positive, particularly for HSP90, cHSP70, and HSP27. CONCLUSION: These results indicate that normal and atopic keratoconjunctivitis epithelia express HSP90 and HSP27 and some form of HSP65 and HSP70. The differences between normal, atopic keratoconjunctivitis, and OCP stromal staining suggest an upregulated expression of HSP90, cHSP70, and HSP27 at the site of inflammation in OCP, the stroma, from cytokine release. The striking presence of HSP in the conjunctival vascular endothelium from OCP patients suggests a previously unappreciated role of the vasculature in OCP.

The role of macrophages in the pathogenesis of HSV-1 induced chorioretinitis in BALB/c mice.

PURPOSE: To examine the effects of modification of immune effector cells, including macrophages, in the pathogenesis of herpes simplex virus retinitis in BALB/c mice. METHODS: Two intravitreal injections (2 microliters each) of anti-CD11b monoclonal antibody (mAb) [13 micrograms/microliters] were administered to the contralateral eyes of 10 BALB/c mice on days 6 and 8 after HSV inoculation into the right anterior chamber (AC) with HSV-1. A control group consisted of mice injected with anti-HLA-DR mAb in the same fashion. Specific macrophage depletion was performed in an additional group of 12 BALB/c mice by intravenous (i.v.) injection of dichloromethylene diphosphonate (Cl2MDP)-liposomes 7 days before AC HSV-1 inoculation into the eye. Control group consisted of mice receiving i.v. PBS-liposomes. Mice were clinically observed for 14 days postinfection, and the incidence of chorioretinal disease was confirmed by histopathologic studies. RESULTS: Intravitreal injections of anti-CD11b mAb produced a dramatic suppression of the contralateral retinal necrosis (2 of 10 mice) compared to 9 of 10 controls receiving an irrelevant antibody therapy (P < 0.05). Mice treated with i.v. Cl2MDP-liposomes also showed a significant inhibition of the development of contralateral chorioretinitis, with only 3 of 12 mice developing retinal disease compared to 9 of 12 mice from the control group (P < 0.05). FACS analysis performed on peripheral blood and spleen cells showed a significant depletion of Mac-1+ cells of Cl2MDP-liposome-treated but not of PBS-liposome-treated mice (controls). CONCLUSION: Intravitreal anti-CD11b mAb therapy, a broadly directed depletion strategy against many effector cells (macrophages, granulocytes, natural killer cells, and even cytotoxic T-cells) was most efficient in suppressing the HSV-1 induced contralateral disease. A more specific technique (i.v. Cl2MDP-liposome therapy) to deplete macrophages also produced a significant inhibition of HSV-1 induced contralateral chorioretinitis. These findings suggest that macrophages are important participants in the effector phase of the destructive inflammatory immune response induced by HSV-1 in the eye.