Amputation-free survival in the long-term follow-up and gender-related characteristics in patients revascularized for critical limb ischemia.

OBJECTIVE: Patients with Critical Limb Ischemia (CLI) present a high risk of cardiovascular events and death. Revascularization is the cornerstone of therapy to relieve ischemic pain and prevent limb loss. Literature data suggest that women tend to present with worse outcomes after revascularization. The aim of the present study is to determine amputation-free survival in a long-term follow-up in women and men following endovascular revascularization procedure for CLI. METHODS: From November 2013 to December 2020, 357 consecutive patients were retrospectively included. Clinical and biological parameters were recorded at baseline before endovascular revascularization. During follow-up until February 2023, overall survival and amputation-free survival (freedom from major amputation) were analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed to study the parameters associated with amputation-free survival. A P<0.05 was considered as statistically significant. RESULTS: A total of 357 consecutive patients were included, 189 men and 168 women with CLI, with a mean age of 78.6±12 years. Treated hypertension (79%), diabetes mellitus (48%), coronary artery disease (39%) and protein malnutrition (61%) were the most prevalent comorbidities. Women were older than men with a mean age of 82.4±11.4 years (versus 75.4±11 years in men) and presented more frequently with protein malnutrition (70% of women). Prevalence of diabetes, tobacco use and history of coronary heart disease were significantly higher in men. During the 10-year follow-up period, 241 patients had died (68%) and 38 (11%) underwent major amputation, of whom 22 patients were still alive on February 2023. Median survival was 35.5 months [IQR: 29.5; 43] in the overall population, 38.5 [32; 50.4] months in women and 33.5 months [24.7; 43.5] in men. No gender-related differences were noted according to peri-procedural complications, survival probability and amputation-free survival. In multivariate analysis for amputation-free survival, age, previous coronary heart disease, C-reactive protein level, left ventricular ejection fraction (LVEF)<60% and albumin level<35g/L were correlated with poor outcome. In particular, protein malnutrition, as a treatable risk factor, appears significantly correlated with poor outcome in both men and women (HR=2.50 [1.16;5.38], P=0.0196 in men; HR=1.77 [1.00;3.13], P=0.049 in women). CONCLUSION: The present results highlight that mortality in patients after endovascular revascularization remains high with a mortality rate of 28% at 1 year, 40% at 2 years and 51% at 3 years. Women represented a distinct population, almost 10-year older than their male counterparts, with more prevalent protein malnutrition. However, no gender-related difference was noted according to amputation-free survival on the long-term follow-up. Associated risk factors are mainly age, a history of coronary heart disease, pre-procedural inflammatory syndrome and protein malnutrition. Correction of malnutrition could have the potential to improve functional and general long-term prognosis in patients with CLI together with optimal medical and interventional management.

Fissurectomy with mucosal advancement flap anoplasty: The end of a dogma?

INTRODUCTION: The goal was to compare fissurectomy with mucosal advancement flap anoplasty to fissurectomy alone in the surgical treatment of anal fissure. PATIENTS AND METHODS: This study included patients who underwent surgery in 2019 for solitary, idiopathic, non-infected, posterior anal fissure, after failure of medical treatment. The choice to perform advancement flap anoplasty was based on surgeon preference and did not depend on the fissure itself. The main endpoint was the time to relief of pain. RESULTS: Of 599 fissurectomies performed during the study period, 226 patients (37.6% women, mean age 41.7±12.0 years old) underwent fissurectomy alone (n=182) or associated with advancement flap anoplasty (n=44). The two groups differed as to their sex ratio (33.5 vs. 54.5% women, P=0.01), body mass index (25.3±4.0 vs. 23.6±3.9, P=0.013) and Bristol score (3.2 vs. 3.4, P=0.038). Time to relief of pain, time to disappearance of bleeding and time to healing were 1.1 (0.5-2.3), 1.0 (0.5-2.1) and 2.0 (1.1-3.6) months, respectively. The rate of healing was 93.8% and the complication rate was 6.2%. The differences between the two groups for these outcomes were not statistically significant. The risk factors associated with absence of healing were age ≥ 40 years (Odds ratio (OR): 3.84; 95% CI, 1.12-17.68) and pre-surgical duration of fissure<35.6 weeks (OR: 6.54; 95% CI: 1.69-43.21). CONCLUSION: Mucosal advancement flap anoplasty does not provide any added value to fissurectomy alone.

Deep remission improves the quality of life of patients with Crohn's disease and anoperineal fistula treated with darvadstrocel: results of a French pilot study.

BACKGROUND: The injection of allogeneic adipose tissue-derived mesenchymal stem cells (MSC) into anal fistulas in patients with Crohn's disease has never been evaluated in "real-life" conditions in France. METHODS: We prospectively studied the first patients receiving MSC injections at our center and undergoing 12 months of follow-up. The primary endpoint was the clinical and radiological response rate. The secondary endpoints were symptomatic efficacy, safety, anal continence, quality of life (Crohn's anal fistula-quality of life scale, CAF-QoL), and predictive factors of success. RESULTS: We included 27 consecutive patients. The complete clinical and radiological response rates at M12 were 51.9% and 50%, respectively. The combined complete clinical-radiological response (deep remission) rate was 34.6%. No major adverse effects or changes in anal continence were reported. The perianal disease activity index decreased from 6.4 to 1.6 (p < 0.001) for all patients. The CAF-QoL score also decreased from 54.0 to 25.5 (p < 0.001). At the end of the study, M12, the CAF-QoL score was significantly lower only in patients with a complete combined clinical-radiological response relative to those without a complete clinical-radiological response (15.0 versus 32.8, p = 0.01). Having a multibranching fistula and infliximab treatment were associated with a combined complete clinical-radiological response. CONCLUSIONS: This study confirms reported efficacy data for the injection of MSC for complex anal fistulas in Crohn's disease. It also shows a positive impact on the quality of life of patients, particularly those for whom a combined clinical-radiological response was achieved.

Hormone-dependent gynaecological disorders and contraceptive modalities in women with a history of venous thromboembolic event: The THROMBOGYN study.

CONTEXT: Hormone-dependent gynaecological disorders, such as polycystic ovary syndrome (PCOS) or endometriosis, have been recently discussed as potential risk factors for venous thromboembolism (VTE). Combined hormonal contraceptive (CHC) therapy, which is a well-known risk factor for VTE, is usually used to alleviate symptoms related to these gynaecological disorders. Nevertheless, prevalence of hormone-dependent gynaecological disorders at the time of VTE event and the management of hormonal contraceptives are not well known. OBJECTIVE: To assess retrospectively the prevalence of hormone-dependent gynaecological disorders in patients with VTE event and the hormonal therapy at the time of VTE event and at the time of inclusion in the present study. METHODS: Women aged between 18 to 50-year-old who were hospitalized at Saint-Joseph Hospital (Paris) for a VTE event from January 1st, 2016 to December 31st, 2020 were included in this retrospective observational study. RESULTS: In total, 125 women were included. At the time of VTE event, mean age was 39-years-old (±8) and mean body mass index (BMI) 26kg/m2 (±8). Pulmonary embolism represented more than two third (68%) of VTE events. Fourteen women (11%) had PCOS and among them, 6 (43%) were using CHC. Eleven women (9%) had endometriosis and among them, 1 (9%) was using CHC. Women with PCOS appeared to be younger at the time of VTE compared to non-PCOS women (mean age 32 years (±6.0) vs. 40 years (±8.0), respectively, P<0.001), whereas women with endometriosis were older with a mean age of 43-year-old (±7.8), which did not differ significantly from women without endometriosis. Among PCOS women, 1 (7%) VTE event was idiopathic, whereas among those with endometriosis, 5 (46%) VTE events were idiopathic. Regarding contraceptive use at the time of inclusion, with a mean delay between VTE event and inclusion of 3 years (±1), 1 woman pursued CHC, 35 (28%) used non-hormonal contraceptive. Seventy-three women (58%) were aware of hormonal contraindications due to VTE event. CONCLUSION: The present study, including 125 young women with a mean age of 39 years, allowed a description of gynecological pathologies and history of contraceptive use potentially involved in VTE events.

Peri-procedural complications following endovascular revascularization for critical limb ischemia.

OBJECTIVE: Revascularization procedures are considered the cornerstone of therapy in patients with critical limb ischemia (CLI) and multiple procedures are often required to attain limb salvage. The aim of the present study is to determine the prevalence of peri-procedural complications after endovascular procedure, and to determine the clinical and biological characteristics of patients associated to the risk of peri-procedural complications. METHODS: From November 2013 to May 2021, 324 consecutive patients were retrospectively included, of whom 99 underwent more than one revascularization procedure for contralateral CLI or clinical recurrence of CLI. A total of 532 revascularizations were performed. Clinical and biological parameters were recorded at baseline before endovascular revascularization. The occurrence of a peri-procedural complication (local complications, fatal and non-fatal major bleeding or cardiovascular events) was recorded up to 30days after revascularization. Univariate and multivariate analyses were performed to study the parameters associated with per-procedural complications. A P<0.05 was considered as statistically significant. RESULTS: A total of 324 consecutive patients were included, 177 men and 147 women with CLI, with a mean age of 77.6±11.9years. Most of these patients had cardiovascular comorbidities (41% with a history of coronary heart disease, 78% treated hypertensive patients, 49% diabetic patients). Peri-procedural mortality occurred in 13 patients (4%) and 9 patients (2.8%) experienced major amputation at one-month following revascularization. Among the 532 revascularization procedures, 99 major bleeding events (22.8% of the cohort population) and 31 cardiovascular events (8.6% of the cohort population), were recorded in the peri-procedural period. Cardiovascular events were associated with peri-procedural mortality. Complications at the puncture site occurred during 38 of the 532 procedures (10.2% of the cohort population). Compared with patients undergoing a single revascularization procedure, patients with multiple procedures presented a higher risk of major bleeding events (48.5% vs. 11.6%, P<0.0001) and access site complications (20.2% vs. 5.78%, P<0.0001). In multivariate analysis, pulse pressure <60mmHg and hemoglobin level <10g/dl were correlated with the occurrence of major bleeding events; left ventricular ejection fraction<60% and the absence of statin treatment were correlated with the occurrence of cardiovascular complications; a high chronological rank of revascularization was correlated with the occurrence of local complication. Finally, age and gender were not associated with the occurrence of peri-procedural complication. CONCLUSION: The present results highlight that multiple revascularization procedures for limb salvage are required in almost one third of the population with critical limb ischemia and were associated with the risk of major bleeding events and access site complications. The most frequent complications of peripheral vascular interventions were major bleeding events. Adverse cardiovascular events were related with peri-procedural mortality. Anemia, blood pressure, left ventricular ejection fraction and statin treatment are important parameters to consider for peri-procedural outcomes, independently of age, gender and the chronological rank of revascularization procedure.

Factors associated with psychological symptoms in hospital workers of a French hospital during the COVID-19 pandemic: Lessons from the first wave.

PURPOSE: The COVID-19 pandemic has put hospital workers around the world in an unprecedented and difficult situation, possibly leading to emotional difficulties and mental health problems. We aimed to analyze psychological symptoms of the hospital employees of the Paris Saint-Joseph Hospital Group a few months after the 1st wave of the pandemic. PARTICIPANTS AND METHODS: From July 15 to October 1, 2020, a cross-sectional survey was conducted among hospital workers in the two locations of our hospital group using the Hospital Anxiety and Depression Scale (HADS) and Post-Traumatic Stress Disorder (PTSD) Checklist (PCL) to measure anxiety, depression, and PTSD symptoms. Factors independently associated with these symptoms were identified. RESULTS: In total, 780 participants (47% caregivers, 18% health administrative workers, 16% physicians, and 19% other professionals) completed the survey. Significant symptoms of anxiety, depression, and PTSD were reported by 41%, 21%, and 14% of the participants, respectively. Hierarchical regression analysis showed a higher risk of having psychological symptoms among those (1) who were infected by SARS-CoV-2 or had colleagues or relatives infected by the virus, (2) who retrospectively reported to have had an anxious experience during the first wave, and (3) with a previous history of burnout or depression. In contrast, job satisfaction appeared to be a protective factor. Overall, hospital workers showed the statistically same levels of anxiety, depression, and PTSD symptoms, regardless of their profession and whether they had worked in units with COVID-19 patients or not. CONCLUSIONS: Our cross-sectional survey of 780 hospital workers shows that after the first wave, hospital employees had a significant burden of mental health symptoms. Specific preventive measures to promote mental well-being among hospital workers exposed to COVID-19 need to be implemented, first among particularly vulnerable staff, and then, for all hospital staff for whom anxiety is detected early, and not only those who were directly exposed to infected patients.

Rufinamide in refractory childhood epileptic encephalopathies other than Lennox-Gastaut syndrome.

BACKGROUND: To report on the first multicenter Italian experience with rufinamide as adjunctive drug in children, adolescents and young adults with refractory childhood-onset epileptic encephalopathies other than Lennox-Gastaut syndrome. METHODS: Thirty-eight patients (19 males, 19 females), aged between 4 and 34 (mean 13.7 ± 8.3, median 12.5), all affected by different types of childhood-onset refractory epileptic encephalopathies other than Lennox-Gastaut syndrome, were treated with rufinamide as adjunctive drug for a mean period of 11.4 months (range 3-26 months). RESULTS: Fifteen of 38 patients (39.5%) had a ≥ 50% seizure reduction in countable seizures. Complete seizure freedom was achieved in one of these patients (2.6%). Three patients (7.9%) had a 25-49% seizure reduction, whilst seizure frequency remained unchanged in 15 (39.5%) and increased in five patients (13.1%). Eleven patients (28.9%) reported adverse side effects. Vomiting was reported in five patients (13.1%); drowsiness, decreased appetite and irritability with migraine manifested in other four patients. They were transient and mild in all cases. CONCLUSION: Rufinamide may be an effective and well-tolerated adjunctive drug for the treatment of refractory childhood-onset epileptic encephalopathies other than Lennox-Gastaut syndrome. Rufinamide was most effective in patients with drop-attacks and (bi)frontal spike-wave discharges.

Transcription of potato spindle tuber viroid by RNA polymerase II starts predominantly at two specific sites.

Pospiviroidae, with their main representative potato spindle tuber viroid (PSTVd), are replicated via a rolling circle mechanism by the host-encoded DNA-dependent RNA polymerase II (pol II). In the first step, the (+)-strand circular viroid is transcribed into a (-)-strand oligomer intermediate. As yet it is not known whether transcription is initiated by promotors at specific start sites or is distributed non-specifically over the whole circle. An in vitro transcription extract was prepared from a non-infected potato cell culture which exhibited transcriptional activity using added circular PSTVd (+)-strand RNA as template. In accordance with pol II activity, transcription could be inhibited by alpha-amanitin. RT-PCR revealed the existence of at least two different start sites and primer extension identified these as nucleotides A(111) and A(325). The sequences of the first 7 nt transcribed are very similar, (105)GGAGCGA(111) and (319)GGGGCGA(325). GC-boxes are located at a distance of 15 and 16 nt upstream, respectively, in the native viroid structure, which may act to facilitate initiation. The GC-boxes may have a similar function to the GC-rich hairpin II in the (-)-strand intermediate, as described previously. The results are compared with the corresponding features of avocado sunblotch viroid, which belongs to a different family of viroids and exhibits different transcription initiation properties.

RNA structural features responsible for potato spindle tuber viroid pathogenicity.

The native structure of potato spindle tuber viroid (PSTVd) contains a series of short double helices and small internal loops that are organized into five structural domains. Nucleotides within the pathogenicity domain are known to play a critical role in modulating PSTVd symptom expression, and it has been suggested that disruption of a comparatively unstable "premelting region" within the pathogenicity domain may be required for disease induction. We have used a combination of quantitative bioassays, temperature gradient gel electrophoresis of circularized RNA transcripts, and thermodynamic calculations to compare the biological and structural properties of 12 representative PSTVd sequence variants. Certain mutations appeared to act indirectly, downregulating pathogenicity by suppressing the rate of PSTVd replication/accumulation. The effects of other mutations appeared to be more direct, but there was no consistent correlation between symptom severity and melting temperature. Taking into account the three-dimensional shape of RNA helices, comparison of the optimal secondary structures for these variants point to major differences in the geometry of their pathogenicity domains; i.e., variants producing intermediate symptoms possess a linear arrangement of three consecutive helices, whereas for variants producing mild or severe symptoms this domain is bent in opposing directions. Such alterations in RNA structure together with concomitant alterations in RNA-protein interaction(s) may be the primary cause of viroid pathogenicity.

Interdependence of pathogenicity and replicability with potato spindle tuber viroid.

After the unexpected appearance of lethal symptoms on tomato plants infected with the PSTVd strain Intermediate Di, viroids were isolated and sequenced. It was found that a new strain, named RG 1, had been generated spontaneously in our greenhouse. In a different series of plant passages two new strains, named QF A and QF B, were detected which coexisted with the wild-type strain Di. Strains QF A and QF B showed intermediate symptoms when inoculated separately. In order to confirm the working hypothesis that the more pathogenic strain outcompetes the less pathogenic strain but strains of similar pathogenicity might coexist in the host, strains of different pathogenicity were mixed for inoculation in a ratio from 1:1 to 1:100 (more pathogenic:less pathogenic). The concentrations of the individual strains were determined 6 weeks postinfection with the method of nondenaturing polyacrylamide gel electrophoresis, and the working hypothesis was confirmed. The total concentrations of viroids in infected plants were very similar, irrespective of whether severe, intermediate, or mild strains or mixtures of different strains were present. The mutations in all new strains (3 in RG 1, 2 in QF A, 3 in QF B) were located in the so-called virulence-modulating region. The mutations of strain RG 1 influenced dramatically the thermodynamic stability of the native rod-like structure, as determined experimentally by temperature-gradient gel electrophoresis. Since during replication a multihairpin structure is generated transiently which is transformed afterwards into the rod-like structure, a lower thermodynamic stability of the rod-like structure leads to a higher accumulation of the transient structure. It is assumed that the transient structure, which is active in replication as shown earlier, is essential also in pathogenesis. This model explains the experimentally determined interdependence between pathogenicity and replicability of PSTVd strains.

Pneumocystis carinii pneumonia in patients with primary brain tumors.

All histologically documented episodes of Pneumocystis carinii pneumonia in adult patients with primary brain tumors treated at Memorial Sloan-Kettering Cancer Center, New York, NY, since 1981, were retrospectively reviewed. Pneumocystis carinii pneumonia was histologically documented 11 times in 10 patients. During the same 8-year interval, approximately 587 adults were seen at the center for a brain tumor, 90% of whom received ongoing therapy. Therefore, in at least 1.7% (10/587) of our patients with brain tumors, P carinii pneumonia developed. The median duration of dexamethasone therapy at the onset of P carinii pneumonia symptoms was 2.75 months. Symptoms began during tapering of steroid therapy in eight episodes. Bronchoscopy was diagnostic in the eight cases in which it was performed. Four episodes (40%) were fatal. Trimethoprim-sulfamethoxazole prophylaxis may be indicated in some patients with brain tumors, especially during tapering of steroid therapy.

The incidence and significance of Staphylococcus aureus in respiratory cultures from patients infected with the human immunodeficiency virus.

This study assessed the incidence and clinical significance of recovery of Staphylococcus aureus from the respiratory tract of patients infected with the human immunodeficiency virus (HIV). In a retrospective review of 129 consecutive episodes of respiratory disease in HIV-seropositive patients where respiratory tract cultures were obtained, S. aureus was recovered in 30 (23%) of the episodes. Twenty-nine of these were evaluated in this study, and the recovery of S. aureus was found to represent pneumonia in 8 cases (28%), to be of indeterminate significance in 18 cases (62%), and to represent colonization in 3 cases (10%). Episodes of S. aureus pneumonia were usually community-acquired (seven of eight episodes) and had an acute or subacute clinical presentation. Fever and physical signs of pneumonia were present in all patients. Chest radiographic presentations varied, but local infiltrates were seen in seven of eight episodes. Concomitant pulmonary disorders were common (seven of eight episodes). All patients were appropriately treated; five patients recovered and three died, giving a mortality rate of 38%. We conclude that S. aureus is a frequent isolate from respiratory tract cultures of HIV-seropositive patients referred for evaluation of pulmonary disease. It can cause a pneumonia with a high mortality rate, as it did in 6% of all episodes of pulmonary disease reviewed in this study. Clinicians should be aware that HIV-seropositive patients may develop respiratory disease secondary to S. aureus infection and that when this organism is suspected, appropriate antibiotic therapy should be instituted.

Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin.

STUDY OBJECTIVE: To assess the efficacy of the combination of the antiviral agent ganciclovir (9-1,3 dihydroxy-2-propoxymethylguanine) and high-dose intravenous immune globulin for treating cytomegalovirus interstitial pneumonitis after allogeneic bone marrow transplantation. DESIGN: Nonrandomized prospective trial of combined treatment with two drugs; findings in these patients were compared with those in control patients treated with either of the two drugs alone. SETTING: Medical, pediatric, and intensive care units of a tertiary-care cancer treatment center. PATIENTS: Consecutive cases of 10 patients in the study group and of 11 patients in a historical control group with evidence of cytomegalovirus pneumonia after bone marrow transplantation for treatment of leukemia or congenital immune deficiency. INTERVENTIONS: Study Group (10 patients): ganciclovir, 2.5 mg/kg body weight, three times daily for 20 days, plus intravenous immune globulin, 500 mg/kg every other day for ten doses. Patients were then given ganciclovir, 5 mg/kg.d three to five times a week for 20 more doses, and intravenous immune globulin, 500 mg/kg twice a week for 8 more doses. Control Group (11 patients): ganciclovir alone (2 patients), 5 mg/kg twice a day for 14 to 21 days; cytomegalovirus hyperimmune globulin (5 patients), 400 mg/kg.d for 10 days; and intravenous immune globulin (4 patients), 400 mg/kg.d for 10 days. MEASUREMENTS AND MAIN RESULTS: Responses were observed in all patients treated with combination therapy; 7 of 10 patients were alive and well, and had no recurrence of disease at a median of 10 months after therapy. No therapeutic benefit was observed, and none of the 11 patients treated with either ganciclovir or intravenous immune globulin alone survived (P = 0.001 by Fisher exact test). CONCLUSIONS: Ganciclovir, when combined with high-dose intravenous immune globulin, appears to have significantly altered the outcome of patients with cytomegalovirus pneumonia after allogeneic bone marrow transplantation.

Bacterial and fungal pneumonias.

Bacterial pneumonias occur with increased frequency and can be associated with increased morbidity in the HIV-infected population compared with normals. The pathogens that most frequently cause community-acquired pneumonias are S. pneumoniae, H. influenzae, and occasionally S. aureus. These pneumonias usually respond to appropriate antibiotic therapy; however, patients diagnosed with bacterial pneumonias are at increased risk for subsequent episodes. Nosocomial pneumonias, by contrast, are usually caused by gram-negative organisms and have a high mortality. Fungal pneumonias also have an increased incidence in AIDS patients, and usually occur in the setting of disseminated disease. Infections caused by C. neoformans, H. capsulatum, and C. immitis often recur despite a good initial response to amphotericin B. Maintenance therapy with an antifungal agent is therefore recommended.

Hydrogen peroxide release by alveolar macrophages from sarcoid patients and by alveolar macrophages from normals after exposure to recombinant interferons alpha A, beta, and gamma and 1,25-dihydroxyvitamin D3.

We measured H2O2 release by human alveolar macrophages (AM) from normals and sarcoid patients in suspension immediately after bronchoalveolar lavage in the presence and absence of the triggering agent, phorbol myristate acetate (PMA). AM from 11 sarcoid patients produced a mean (+/- SE) of 21.7 +/- 2.3 and 5.9 +/- 3.4 nmol H2O2/10(6) macrophages in the presence and absence of PMA, respectively. By contrast, AM from normals (n = 6) produced 9.8 +/- 1.7 and 1.6 +/- 0.7 nmol H2O2/10(6) macrophages with and without PMA, respectively. Macrophage activation, as monitored by H2O2 production, did not correlate with the angiotensin-converting enzyme levels, the result of gallium-67 scans, or the percent of lymphocytes in the bronchoalveolar lavage. To determine whether AM from normals could be stimulated to increase their H2O2 production to the level seen in patients with sarcoid, we measured H2O2 released by adherent AM after incubation in each of four potential activating agents: recombinant interferons alpha A, beta, gamma (rIFN alpha A, rIFN beta, and rIFN gamma, respectively), and 1,25-dihydroxyvitamin D3. H2O2 release in the range seen in sarcoid patients could be induced in PMA-triggered AM from normals by rIFN gamma in a time- (t1/2 approximately 1 d) and dose-dependent fashion (threefold increase, EC50 5 antiviral U/ml) and by rIFN alpha A and rIFN beta at higher concentrations, but not by 1,25-dihydroxyvitamin D3.

Compartmentalized regulation of macrophage arachidonic acid metabolism.

We show that downregulation of arachidonic acid (20:4) metabolism which occurs following i.p. injection of C. parvum can occur in a single, localized macrophage population, and is therefore unlikely to be mediated solely by a systemic factor.

The alveolar macrophage.

The alveolar macrophage is one of the few tissue macrophage populations readily accessible to study both in the human and in animals. Since harvesting of these cells by bronchoalveolar lavage was first described in 1961, alveolar macrophages have been extensively investigated. This population is the predominant cell type within the alveolus, and undoubtedly serves as the first line of host defense against inhaled organisms and soluble and particulate molecules. Early studies focussed on this endocytic role and delineated the cells' phagocytic and microbicidal capacities. More recent investigations demonstrated an extensive synthetic and secretory repertoire including lysozyme, neutral proteases, acid hydrolases and O2 metabolites. In addition, the complex immunoregulatory role of the macrophage has also been appreciated. These cells have been shown to produce a wide variety of pro- and anti-inflammatory agents including arachidonic acid metabolites of the cyclooxygenase and lipoxygenase pathways, cytokines which modulate lymphocyte function and factors which promote fibroblast migration and replication.