Hemophagocytic syndrome in patients infected with the human immunodeficiency virus: A study of 15 consecutive patients.

OBJECTIVE: Hemophagocytic syndrome (HPS) is characterized by various clinical and biological data derived from cytokine hyperproduction and cell proliferation. The objectives of this study were to evaluate the epidemiological, etiological, clinical and evolutionary characteristics of patients diagnosed with hemophagocytic syndrome and HIV infection, as well as their comparison with data from the literature. METHODS: A retrospective descriptive observational study was performed, including all adult patients with a diagnosis of HPS and HIV infection treated in the Infectious Diseases and Tropical Medicine Unit of the Hospital Universitario Insular, Las Palmas, Gran Canaria from June 1, 1998 to December 31, 2018. RESULTS: An analysis of this series of case reports of 15 patients showed a higher percentage of males than females, with a mean age of 42 years. With respect to the diagnostic criteria for HPS, presence of fever, cytopenias and hyperferritinemia were a constant in all patients. Clinical neurological manifestations were frequent and clinical respiratory signs and symptoms absent. HPS was confirmed in some patients who were not severely immune-depressed and had undetectable viral loads. Furthermore, 40% of cases were not receiving ART. The most frequent triggering causes of HPS were viral, especially HHV-8. In addition, two new HPS triggers were identified: Blastocystis dermatitidis and Mycobacterium chelonae. CONCLUSIONS: Administration of treatment in HPS is arbitrary. This, together with the high mortality rate and the fact that it is underdiagnosed, indicates the importance of conducting future studies.

Fake imported tropical diseases: A retrospective study.

OBJECTIVE: When we evaluate a patient with a suspected imported disease we cannot forget to include any autochthonous causes that may mimic imported pathologies to avoid misdiagnosis and therapeutic delay. METHODS: A descriptive longitudinal retrospective study was designed with patients in whom an imported disease was suspected but who were finally diagnosed with autochthonous processes. The patients were selected from two internal medicine practices specializing in tropical diseases between 2008-2017 in Spain. RESULTS: We report 16 patients, 11 (68.7%) were males, and the mean age was 43.4 ± 13.7 years old. Thirteen patients (81.2%) were travellers. Half of the patients were from Latin America, 7 (43.5%) were from Africa, and 1 (6.2%) was from Asia. The time from trip to evaluation ranged between 1 week and 20 years (median, 4 weeks), and the mean time from evaluation to diagnosis was 58.4 ± 100.9 days. There were 5 (31.2%) cases of autochthonous infection, 5 (31.2%) cases of cancer, 2 (12.5%) cases of inflammatory disease, and 2 (12.5%) cases of vascular disease. CONCLUSIONS: Travel or migration by a patient can sometimes be a confusing factor if an imported disease is suspected and may cause delays in the diagnosis and treatment of an autochthonous disease. We highlight that 1/3 of the patients with autochthonous diseases in this study had cancer. The evaluation of imported diseases requires a comprehensive approach by the internist, especially if he specializes in infectious and/or tropical diseases and is, therefore, the best qualified to make an accurate diagnosis.

Evaluation of the role of angiogenic factors in the pathogenesis of schistosomiasis.

Schistosomiasis is one disease produced by helminths, which affect many people in tropical areas. Granuloma formation is the main mechanism involved in the pathogenesis of this disease. Experimental studies have demonstrated angiogenesis (blood vessels formation from pre-existing vessels) in the initial phase of granuloma formation. In the present work, VEGF (vascular endothelial growth factor) levels were analyzed in sera from people diagnosed with different helminthic infections. Patients with schistosomiasis and filariasis had significantly high VEGF levels in compared with healthy people and patients diagnosed with hookworms. In addition, the effects of angiogenesis inhibition using anti-angiogenic factors (endostatin) were evaluated in a schistosomiasis murine model. A lesion decrease was observed in mice infected with Schistosoma mansoni and treated with endostatin. Finally, mechanisms of angiogenesis induction were studied and observed that cercariae antigens stimulated the angiogenic factors by host alveolar macrophages.

Role of angiogenic factors in acute experimental Strongyloides venezuelensis infection.

This study aims to investigate the role of angiogenic factors in the pathogenesis of experimental strongyloidiasis. Two complementary approaches were used: Firstly, CD1 mice were treated with endostatin, an angiogenesis inhibitor, and infected with Strongyloides venezuelensis. Also, the mechanisms involved in this process were studied. Parasitological examination revealed a significant decrease in egg per gram of faeces, number of collected larvae from lung tissue and number of collected adult females in mice treated with endostatin. Direct mechanisms with diminution of angiogenesis factors and an indirect mechanism with increase of eosinophil perhaps produced their effect. Secondly, the effect of the antigens responsible for stimulation of angiogenic factors [vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2)] from alveolar macrophages and the mechanisms involved in their production were investigated. Alveolar macrophage cells obtained by bronchoalveolar lavage were incubated at different concentrations of somatic and excretory/secretory antigens of S. venezuelensis. Also, mRNA levels of VEGF and FGF2 in macrophage cells were detected by RT-PCR. L3-PBS larvae antigens induced angiogenic factors. The relationship between angiogenesis factors and nitric oxide has been observed using nitric oxide synthase inhibitors.

Trichinella: differential expression of angiogenic factors in macrophages stimulated with antigens from encapsulated and non-encapsulated species.

The newborn larval stage of Trichinella spiralis enters the host striated skeletal muscle cell resulting in the formation of the nurse cell. Vascular Endothelial Growth Factor (VEGF) was detected in cells in the area immediately surrounding the nurse cells. However, no data are available on the antigens involved, the role of other angiogenic factors or the relationship of angiogenesis with Nitric Oxide (NO) production. Using macrophage cell culture we study the effect of different Trichinella L1 antigens from one encapsulated (T. spiralis) and one non-encapsulated (Trichinellapseudospiralis) on the expression of VEGF and basic Fibroblast Growth Factor (FGF2). Also, we investigate the relationship between the production of NO and angiogenic mediators. The results show that encapsulated and non-encapsulated Trichinella species are different in their capacity to stimulate the expression of VEGF and FGF2 from host macrophages. Finally, there is no relationship between angiogenic factors and NO production by T. spiralis antigen.

Elevated non-transferrin bound iron in the lungs of patients with Pneumocystis carinii pneumonia.

OBJECTIVE: The aim of the present work was to determine the concentrations of iron and iron-binding proteins in the lungs of patients suffering from Pneumocystis carinii (PCP), which is crucial for justifying the treatment with iron-chelating agents in this disease. PATIENTS AND METHODS: Bronchoalveolar lavage was performed in 10 HIV patients with PCP and five healthy controls. Total iron and iron-binding proteins (transferrin, ferritin and lactoferrin) were measured in acellular bronchoalveolar lavage fluid (BALF) in both groups. Iron was determined by atomic absorption spectrometry; transferrin and lactoferrin were measured using specific enzyme-linked immunosorbent assays (ELISA); and ferritin concentration was quantified by automated immunonephelometry. RESULTS: Our findings in patients with PCP demonstrated a six- to seven-fold increase of total iron levels and an eight-fold increase of ferritin in bronchoalveolar lavage fluid when compared with controls. No significant differences were found in transferrin or lactoferrin levels. Moreover, our results suggest that this iron is non-transferrin bound. CONCLUSION: Non-transferrin bound iron is increased in the lower respiratory tracts of PCP patients. This finding would lend experiment support to the use of iron-chelating agents in this disease.

Effect of cyclosporin A on inflammatory cytokine production by human alveolar macrophages.

Cyclosporin A (CsA) is an immunomodulator drug that has been used in the treatment of several types of advanced pulmonary interstitial disease. This beneficial effect occurs mainly in circumstances in which alveolitis due to CD4 lymphocytes is absent, suggesting that CsA acts on other types of cells. The present study was undertaken to determine the effect of CsA on inflammatory cytokine secretion by human alveolar macrophages (AMs). Human AMs were collected by bronchoalveolar lavage from four control subjects and 13 patients with interstitial lung disease. Purified human AMs were incubated with different concentrations of CsA (200, 20 and 2 ng ml-1) in the presence or absence of lipopolysaccharide (LPS). Interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 levels were measured in supernatants using specific enzyme-linked immunosorbent assays. It was found that CsA inhibits basal secretion of TNF-alpha and IL-8 at 20 and 200 ng ml-1. However, none of the different concentrations of CsA modified basal secretion of IL-1 beta nor IL-6. By contrast, a lower concentration of CsA (2 ng ml-1) inhibits LPS-stimulated secretion of all inflammatory cytokines. It is concluded that CsA exerts a modest effect on inflammatory cytokine production by human AMs.

Utility of antibodies against a 22 kD molecule of Dirofilaria immitis in the diagnosis of human pulmonary dirofilariasis.

To assess the characteristics of an ELISA test for the diagnosis of human pulmonary dirofilariasis, we studied the sera of 24 subjects with other helmintoses and of 37 patients suffering from non-parasitic focal lung diseases, comparing them with negative and positive sera. ELISA and Western blot with complete somatic antigen and ELISA with protein Di22 (specifically recognized in cases of lung dirofilariasis) were performed. With ELISA SA the false positive rate was 25% in cases with other parasitoses and 30% in cases with focal lung diseases. ELISA Di22 decreases this positivity levels. Only 2 cases with visceral larva migrans (8.3%) and a case with lung nodules metastatic from renal adenocarcinoma (2.7%) were positive. ELISA Di22 therefore greatly decreases the false positive rate of ELISA SA.

[Acute eosinophilic pneumonia in a pregnant woman]. / Neumonía eosinófila aguda en gestante.

Acute eosinophilic pneumonia is a recently described pulmonary phenomenon involving rapidly progressing respiratory insufficiency. Although it can appear at any age, it has never been reported during pregnancy and its impact on gestation is therefore unknown. We describe the clinical signs and course of disease in this first report of acute eosinophilic pneumonia in a pregnant woman. We emphasize the diagnostic utility of bronchoalveolar lavage, the resolution of symptoms without corticoid treatment and, mainly, the absence of adverse repercussions of the disease on pregnancy.

Effect of physical protection on the mesothelial integrity of the pericardium.

BACKGROUND: Mesothelial integrity is essential for the prevention of pericardial adhesions. This study was performed to determine the effect of physical protection of the pericardium on mesothelial integrity. METHODS: A pericardial biopsy specimen was obtained at the time of pericardiotomy (0 minutes) in 10 patients undergoing a cardiac operation for the first time. The left free edge of the pericardiotomy was plicated inward to protect the mesothelium. Biopsy specimens were obtained from the protected and unprotected pericardium at 45 and 90 minutes after the start of extracorporeal circulation. Mesothelial integrity and the local inflammatory response were then assessed and graded histologically. RESULTS: The mesothelium was found to be present in the protected specimens at 0, 45, and 90 minutes, but it was found to be denuded in the unprotected specimens (p = 0.003 at 45 minutes; p = 0.004 at 90 minutes). Local inflammation was totally established in both the protected and unprotected specimens at 45 minutes. CONCLUSIONS: Physical agents appear to be the main factor that is damaging to the pericardial mesothelium, and this is an important concept to be taken into consideration when designing a method to prevent pericardial adhesions.

[Iron metabolism in patient infected by human immunodeficiency virus type 1]. / Metabolismo del hierro en pacientes infectados por el virus de la inmunodeficiencia humana tipo 1.

BACKGROUND: The aim of this work was to assess the major iron metabolism values in patients infected by human immunodeficiency virus (HIV), and to evaluate the correlation between these data and the immunological status of the patients as expressed by CD4 lymphocyte count. PATIENTS AND METHODS: Seventy-one patients infected by HIV (51 men and 20 women) with mean age of 29 years, plus a control group of 32 healthy subjects were studied. Haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, ferritin, transferrin, serum iron, total iron binding capacity and transferrin saturation index were studied in all of them. Erythrocyte sedimentation rate (ESR) and ALT were also determined in order to estimate the ferritin/ALT quotient. RESULTS: Mean haemoglobin concentration in the HIV-infected patients (133 +/- 22 g/L) was significantly lower (p < 0.05) than that of the control group (147 +/- 16 g/L), its decrease correlating in accordance with the CD4-cell count. Serum iron values in HIV infected patients (82 +/- 40 micrograms/L) are significantly lower (p < 0.02) than those of the control subjects (115 +/- 56 micrograms/ dL), decreasing in parallel with the number of CD4 lymphocytes. Serum ferritin of the HIV patients (259 +/- 250 ng/mL) is significantly higher that that of the normal group (95 +/- 73 ng/ mL), increasing with the decrease of CD4 cells. Significant correlation was found between ferritin and CD4 cells (r = 0.46, p < 0.0003) and positive correlation between ferritin and ESR (r = 0.70, p < 0.001) were found. CONCLUSIONS: As HIV infection advances, progressive anaemia is established. The study of iron metabolism in these patients shows a pattern similar to that of the anaemia of chronic diseases, with even higher serum ferritin. These changes might be due to iron sequestration in phagocytic cells induced by release of cytokines.

Action of cyclosporin A on mononuclear phagocytes.

Classically, cyclosporin A has been reported to exert its immunomodulatory action through its effect on T lymphocytes by inhibiting the synthesis of interleukin 2. However, the inhibition of T-lymphocyte activation does not suitably account for all the effects observed following cyclosporin A administration. It is possible that some of them could be due to the action of cyclosporin A on other cells, among which are mononuclear phagocytes. This article offers a detailed review of the consequences of the interaction of cyclosporin A on the capacities (surface antigen expression and production of inflammatory mediators), functions (chemotaxis, phagocytosis, intracellular destruction and cytotoxicity) and actions (antimicrobial defense, antitumor defense and immune cooperation) of these cells. The general conclusion is that the capacities, functions and actions of the macrophages related to non-specific defense are more resistant to cyclosporin A than those related to immunoregulation.

Hydrolytic enzyme of the alveolar macrophage in diffuse pulmonary interstitial disease.

Hydrolytic enzymes [acid phosphatase, beta-glucuronidase, beta-D-N-acetyl glucosaminidase (beta-D-NAGA), lysozyme and angiotensin-converting enzyme (ACE)] are the major constituents of alveolar macrophages (AM). These enzymes play a crucial role in the pathogenesis of interstitial lung diseases. Cell-associated activity of several enzymes in alveolar macrophages obtained from control subjects (n = 5) and patients suffering five representative types of interstitial pulmonary diseases [sarcoidosis (n = 10), extrinsic allergic alveolitis (n = 5), idiopathic pulmonary fibrosis (n = 5), neoplastic infiltration of the lung (n = 5) and Pneumocystis carinii pneumonia (n = 5)] were evaluated. Cells were obtained by bronchoalveolar lavage and isolated by Ficoll-Hypaque gradient. Enzymatic activity was assessed by standardized tests. Bronchoalveolar lavage (BAL) lymphocyte counts were significantly elevated in the patients with active sarcoidosis (median: 57%), allergic extrinsic alveolitis (median: 51%) and neoplastic infiltration (median: 31%) as compared with the other groups, whereas BAL neutrophil and eosinophil counts were significantly elevated in the patients with idiopathic pulmonary fibrosis (neutrophil median: 29%; eosinophil median: 3%). The highest alveolar macrophage enzymatic activities were obtained in the active sarcoidosis group (median ACE: 23.38 microKat 10(-6) AM; median lysozyme: 8.64 nKat 10(-6) AM; median beta-glucuronidase: 324.22 U 10(-6) AM; median acid phosphatase: 0.78 nKat 10(-6) AM; median beta-D-NAGA: 1.85 nKat 10(-6) AM) which was significantly greater than in the control group (median ACE: 6.69 microKat 10(-6) AM; median lysozyme: 1.95 nKat 10(-6) AM; median beta-glucuronidase: 39.88 U 10(-6) AM; median acid phosphatase: 0.38 nKat 10(-6) AM; median beta-D-NAGA: 0.44 nKat 10(-6) AM). However, intracellular lysosomal enzymatic activities of alveolar macrophages from patients with allergic extrinsic alveolitis, a disease in which the degree of alveolar macrophage activation is maximal, were similar to those of the control group. These findings demonstrated a different pattern of expression of alveolar macrophage's hydrolytic enzymes in lymphocytic diffuse pulmonary interstitial disease. In sarcoidotic patients, hydrolytic enzymes were increased whereas in allergic extrinsic alveolitis, hydrolytic enzyme activities were similar to control groups. Indirect data suggest that the release of lysosomal enzymes by alveolar macrophages during allergic extrinsic alveolitis may be a factor involved in the pulmonary lesions appearing in this disease.