Pedro Ruiz

Impaired Function of Macrophage Fcγ Receptors and Bacterial Infection in Alcoholic Cirrhosis

Background Bacterial infection is a frequent and often fatal complication in patients with cirrhosis. Macrophages play an important part in the host defense against infection because their Fcγ receptors recognize antibody-coated bacteria. Methods We prospectively studied macrophage Fcγ-receptor function in vivo and in vitro in 49 patients with alcoholic cirrhosis, 10 alcoholics without cirrhosis, and 20 normal volunteers. Results The clearance of IgG-sensitized autologous red cells was decreased in 37 of the 49 patients with cirrhosis but in none of the subjects without cirrhosis. In the 49 patients clearance was inhibited by a mean (±SE) of 47 ±3 percent at 1 hour and 53 ±3 percent at 1 1/2 hours, as compared with the clearance in the normal controls (P<0.001). The impairment of macrophage Fcγ-receptor-dependent clearance correlated with the degree of liver insufficiency but not with age, sex, nutritional status, HLA haplotype, or the presence of circulating immune complexes. The clearance of unsensitize...

Impaired Function of Macrophage Fcγ Receptors in End-Stage Renal Disease

Infection is a frequent complication in patients undergoing hemodialysis for end-stage renal disease and is the primary cause of mortality among such patients. Macrophages are important in host defense against infection largely because their Fc gamma receptors recognize antibody-coated bacteria. We therefore studied macrophage Fc gamma-receptor function in vivo and in vitro in 56 patients with end-stage renal disease who were on hemodialysis and in 20 healthy volunteers. The clearance of IgG-coated (sensitized) autologous red cells was decreased in 53 patients. The inhibition of clearance in the 56 patients was 52 +/- 3 percent at 1 hour, 41 +/- 5 percent at 1 1/2 hours, and 29 +/- 5 percent at 2 hours (P less than 0.001). The clearance of unsensitized erythrocytes and heat-altered autologous erythrocytes was normal. The impairment of clearance was not correlated with age, sex, nutritional status, HLA haplotype, or the presence of circulating immune complexes. The recognition of these IgG-sensitized red cells in vitro by Fc gamma RI (an Fc gamma-receptor protein that binds monomeric IgG) on blood monocytes from the patients was also significantly decreased (P less than 0.001) but was partially improved by hemodialysis. Nine patients had severe infections during a two-year follow-up period. The clearance of IgG-coated cells in these patients (half-time, 12.9 +/- 1.7 hours) was significantly impaired, as compared with that in the 47 patients without severe infections (half-time, 4.4 +/- 1.8 hours; P less than 0.001). We conclude that macrophage Fc gamma-receptor function is impaired in patients with end-stage renal disease who are undergoing hemodialysis, and that this impairment probably contributes to the observed immunodepression and high prevalence of infection among such patients.

Capit timed tests quantify age-related motor decline in normal subjects.

Slowing of motor performance in human aging is a well demonstrated clinical observation. Age-related motor decline has been also confirmed in animal models including rodents and non human primates. We studied the motor performance of 60 normal subjects (age: 20-87). Motor study included the four timed tests (TT) recommended in CAPIT protocol: pronation-supination (PS), finger dexterity (FD), movement between two points (MTP) or tapping, and walking test (WT). Finally we compared normal controls with a group of 30 patients with Parkinsons disease (PD) of similar age. Age inversely correlated with TT performance in normal subjects (for PS, r:0.33, p<0.01; FD, r:0.44, p<0.0005; MTP, r:0.51, p<0.0001; WT, r:0.59, p<0.0001, Pearson). Our results confirm that motor performance (measured with CAPIT TT) deteriorates linearly with age. Simple tasks, such as CAPIT TT can help to study and quantify age-related motor decline.

Effects of Androgen Treatment on Expression of Macrophage Fcγ Receptors

ABSTRACT Macrophage Fcγ receptors (FcγRs) play an important role in the host defense against infection and in the pathophysiology of immune cytopenias. Modulation of macrophage FcγR expression is a potential therapeutic approach to immune disorders. Glucocorticoids and progesterones decrease macrophage FcγR expression. We assessed the effect of treatment with androgens and antiandrogens on the expression of macrophage FcγRs using an experimental guinea pig model. Four androgens (testosterone, dihydrotestosterone, mesterolone, and danazol) and five antiandrogens (flutamide, nilutamide, cyproterone acetate, spironolactone, and finasteride) were studied. Following in vivo treatment of guinea pigs, we determined the clearance of immunoglobulin G (IgG)-sensitized erythrocytes in vivo, the binding of IgG-sensitized erythrocytes by isolated splenic macrophages, and splenic macrophage FcγR cell surface expression. All of the androgens impaired the clearance of IgG-sensitized erythrocytes by decreasing splenic macrophage FcγR expression. Dihydrotestosterone and mesterolone were more effective than testosterone or dihydrotestosterone. Flow cytometry and fluorescence microscopy with monoclonal antibodies demonstrated that the androgens decreased the cell surface expression of FcγR1,2 more than that of FcγR2. Antiandrogens did not significantly alter macrophage FcγR expression. Nevertheless, antiandrogens counteracted the effects of androgens on macrophage FcγR expression. These data indicate that androgens impair the clearance of IgG-coated cells by decreasing splenic macrophage FcγR expression. Thus, androgens other than danazol are candidate drugs for the treatment of immune disorders.

Mortality and morbidity of newly diagnosed heart failure treated with statins: a propensity-adjusted cohort study.

BACKGROUND The effect of treatment with statins on the prognosis of newly diagnosed heart failure (ndHF) is not established. We evaluate the relationship of commencing treatment with statins (CTS) with the mortality and the morbidity of ndHF, systolic (HF-DSF) and non-systolic (HF-PSF). METHODS Prospective propensity-adjusted cohort study over 5 years on 2573 patients with ndHF. The main outcomes were all-cause and cardiovascular mortality, hospitalizations and visits. We analyze the independent relationship of CTS with the mortality and the morbidity, stratifying patients for cardiovascular co-morbidity, after adjusting for potential confounders. RESULTS 1343 patients (52.2%) CTS, 1071 (39.5%) died, and 1729 (67.2%) were hospitalized. CTS was associated not only with a lower mortality: RR for HF-overall (CI 95%) 0.23 (0.10 to 0.36), RR for HF-PSF 0.34 (0.21 to 0.47), and RR for HF-DSF 0.20 (0.09 to 0.31), but with dose-dependency (statin>20 mg/day vs. statin<=20 mg/day): RR for HF-overall 0.49 (0.33 to 0.67), RR for HF-PSF 0.53 (0.39 to 0.70), and RR for HF-DSF 0.37 (0.26 to 0.52), and with a lower rate of hospitalization (per 100 persons-year): HF-overall (13.3 vs. 18.2), HF-PSF (13.9 vs. 19.7), and HF-DSF (12.7 vs. 16.6), (P<0.001 in all cases), even after adjustment for the propensity to take statins, or other medications, and other potential confounders. CONCLUSION The commencement of treatment with statins is associated with a dose-dependent reduction of the mortality and of the morbidity of patients with ndHF (systolic or non-systolic).

Treatment with Megestrol Acetate Improves Human Immunodeficiency Virus-Associated Immune Thrombocytopenia

ABSTRACT Splenic macrophage Fcγ receptors participate in the pathophysiology of immune cytopenias, and in such disorders, the beneficial effects of glucocorticoids are in part mediated by decreased expression of macrophage Fcγ receptors. In the animal model, progesterones, like glucocorticoids, inhibit expression of these receptors. Megestrol acetate (MA) is a progesterone frequently used for treating human immunodeficiency virus (HIV)-associated anorexia-cachexia. Twenty-eight patients with HIV-associated thrombocytopenia with shortened platelet survival and increased platelet-associated immunoglobulin G (IgG) who were being treated with MA for anorexia-cachexia were prospectively studied for a 6-month period to assess the potential role of progesterones in the treatment of immune thrombocytopenia. Treatment with MA for nonconsecutive periods of 2 months and 1 month significantly increased platelet count and platelet survival without significant alteration of platelet-associated immunoglobulin levels. Of the 28 patients studied, 22 presented a complete response, 19 presented a complete response 1 month after finishing the MA treatment regimen, and 12 remained in complete response for a further month. Expression of Fcγ receptors (FcγRI and FcγRII) by peripheral blood monocytes and the in vitro recognition of IgG-sensitized cells by monocytes were significantly decreased by the MA treatment. Decreased expression and functioning of these receptors significantly correlated with platelet counts and survival times, but no relationship was found with platelet-associated immunoglobulin, circulating immune complexes, body mass index, plasma HIV load, or CD4 lymphocyte levels. These results suggest that treatment with progesterones, like MA, may be an alternative therapy for immune cytopenias, with few side effects.

Evaluation of ActiTrac® (ambulatory activity monitor) in Parkinson's Disease

At present, the evaluation of Parkinsons Disease (PD) relies mainly on Unified Parkinsons Disease Rating Scale (UPDRS). Other objective measures have been proposed, including functional studies, timed tests and ambulatory activity monitors (AAM). We carried out a prospective study to analyze the utility and correlation of the AAM: ActiTrac with UPDRS scores and timed tests in patients with PD. We studied 28 patients with idiopathic PD (age: 62 +/- 11 years; duration of illness: 7.7 +/- 4.4 years; clinical stage 2.3 +/- 0.39). Motor evaluation included UPDRS and five timed tests: Purdue Pegboard test and those proposed in CAPIT protocol, pronation-supination (PS), finger dexterity (FD), movement between two points (MTP) and walking test (WT). Clinical evaluation was performed in off condition, at 9 a.m., (12h off their medication). Finally, ActiTrac was placed on the wrist (more affected side) continuously for at least 72h. ActiTrac activity was correlated (Spearman) with total UPDRS (r: - 0.53, p < 0.005) and motor UPDRS (r:- 0.46, p: 0.01); UPDRS rigidity subscore (r:- 0.52, p < 0.01); UPDRS bradykinesia subscore (r:- 0.48; p:0.01); FD (r: - 0.47 p: 0.01), WT (r: - 0.49, p < 0.01) and Purdue test (r:0.54; p < 0.01). ActiTrac seems to be a reasonably accurate method to evaluate motor activity in PD.At present, the evaluation of Parkinsons Disease (PD) relies mainly on Unified Parkinsons Disease Rating Scale (UPDRS). Other objective measures have been proposed, including functional studies, timed tests and ambulatory activity monitors (AAM). We carried out a prospective study to analyze the utility and correlation of the AAM: ActiTrac® with UPDRS scores and timed tests in patients with PD. We studied 28 patients with idiopathic PD (age: 62 ± 11years; duration of illness: 7.7 ± 4.4years; clinical stage 2.3 ± 0.39). Motor evaluation included UPDRS and five timed tests: Purdue Pegboard test and those proposed in CAPIT protocol, pronation–supination (PS), finger dexterity (FD), movement between two points (MTP) and walking test (WT). Clinical evaluation was performed in off condition, at 9 a.m., (12h off their medication). Finally, ActiTrac® was placed on the wrist (more affected side) continuously for at least 72h. ActiTrac® activity was correlated (Spearman) with total UPDRS (r: � 0.53, p b 0.005) and motor UPDRS (r:� 0.46, p: 0.01); UPDRS rigidity subscore (r:� 0.52, p b 0.01); UPDRS bradykinesia subscore (r:� 0.48; p:0.01); FD (r: � 0.47 p: 0.01), WT (r: � 0.49, p b 0.01) and Purdue test (r:0.54; p b 0.01). ActiTrac® seems to be a reasonably accurate method to evaluate motor activity in PD.