Telomere length dynamics over 10-years and related outcomes in patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been proposed as a disease of accelerated aging. Several cross-sectional studies have related a shorter telomere length (TL), a marker of biological aging, with COPD outcomes. Whether accelerated telomere shortening over time relates to worse outcomes in COPD patients, is not known. METHODS: Relative telomere length (T/S) was determined by qPCR in DNA samples from peripheral blood in 263 patients at baseline and up to 10 years post enrolment. Yearly clinical and lung function data of 134 patients with at least two-time measures of T/S over this time were included in the analysis. RESULTS: At baseline, T/S inversely correlated with age (r = - 0.236; p < 0.001), but there was no relationship between T/S and clinical and lung function variables (p > 0.05). Over 10 years of observation, there was a median shortening of TL of 183 bp/year for COPD patients. After adjusting for age, gender, active smoking and mean T/S, patients that shortened their telomeres the most over time, had worse gas exchange, more lung hyperinflation and extrapulmonary affection during the follow-up, (PaO2 p < 0.0001; KCO p = 0.042; IC/TLC p < 0.0001; 6MWD p = 0.004 and BODE index p = 0.009). Patients in the lowest tertile of T/S through the follow-up period had an increased risk of death [HR = 5.48, (1.23-24.42) p = 0.026]. CONCLUSIONS: This prospective study shows an association between accelerated telomere shortening and progressive worsening of pulmonary gas exchange, lung hyperinflation and extrapulmonary affection in COPD patients. Moreover, persistently shorter telomeres over this observation time increase the risk for all-cause mortality.

In vitro vitamin K3 effect on conjunctival fibroblast migration and proliferation.

PURPOSE: To evaluate the dose effect of vitamin K3 on wound healing mechanisms. METHODS: Conjunctival fibroblasts were incubated for 24 hours. An artificial wound was made and the cells were incubated with fresh medium plus doses of vitamin K3 to be tested. Wound repair was monitored at 0, 18, 24, and 48 hours. Proliferation was measured in actively dividing cells by [(3)H]thymidine uptake. Six different groups were tested: group 1/no drugs added, group 2/ethanol 0.1%, group 3/vitamin K3 1 mg/L, group 4/vitamin K3 2 mg/L, group 5/vitamin K3 4 mg/L, and group 6/vitamin K3 6 mg/L. Each experiment was carried out in triplicate and 4 times. RESULTS: There were no differences among groups at the initial time. In vitro wound repair was slower in groups 4, 5, and 6. There were no differences between control and ethanol groups and between control and vitamin K3 1 mg/L groups. Fibroblast mitogenic activity was statistically decreased in all vitamin K groups; statistical differences were found among vitamin K3 1 mg/mL and higher doses too. In groups 5 and 6, cellular toxicity was presented. CONCLUSIONS: Vitamin K3 is able to inhibit fibroblast proliferation. Vitamin K3 2 mg/L or higher doses inhibit wound healing repair, exhibiting cellular toxicity at 4 and 6 mg/L.

Cell culture propagation modifies the African swine fever virus replication phenotype in macrophages and generates viral subpopulations differing in protein p54.

We have detected 86 African swine fever (ASF) virus-induced proteins in infected pig macrophages by two-dimensional electrophoresis. No differences among protein patterns of wild-type viruses could be observed by this methodology. However, during cell culture adaptation and propagation we have characterized changes in the molecular weight of the ASF virus specified protein p54, which show direct correlation with both size and number of viral subpopulation variants generated during cell culture propagation. Passages in culture appear to select for viral subpopulations that specify p54 proteins with higher molecular weights than the wild-type virus. The virus propagation in cell culture also affected its replication phenotype in pig macrophages decreasing the viral titers in these cells between passage 44 and 81. Nevertheless, the changes observed in p54 did not imply differences in biological properties, such as infectivity, virulence or host cell range among viral clones isolated, each one specifying for only one p54 form with different molecular weight. This protein becomes then a valuable quantification marker to follow evolution and generation of ASF virus diversity in vitro.

Modulation of immune cell populations and activation markers in the pathogenesis of African swine fever virus infection.

African swine fever (ASF) virus induces immune cell alterations that may be detected by changes in peripheral blood cells phenotypic antigens and activation markers which were examined by flow cytometry, analyzing both cell proportion and/or expression intensity of superficial antigens. These studies were conducted in pigs with experimental acute of chronic ASF infection to determine whether changes among important surface activation markers and phenotypic antigens, and their correlative lymph node status, reflected similar or disparate aspects of immune pathology. In acute infection produced by virulent viruses, macrophage and B lymphocyte populations decreased in peripheral blood after a short activation period at the beginning of the infection. A significative decrease of interleukin 2 receptor (IL 2R) expression was also observed in those pigs. These variations correlated with lymph node cell depletion due to an intense lymphoid cell death by apoptosis, affecting mainly the B lymphocyte subpopulation as determined by immunohistochemistry. Nevertheless, pigs infected with an attenuated isolate undergoing chronic persistent infection, presented a distinct pattern of modification, according with a different clinicopathological evolution. Changes consisted in systemic immune activation coincident with the highest viremia titer, with an augmentation in CD8+ T lymphocyte, macrophage, and B cell populations, and MHC (major histocompatibility complex) antigens. Percentage elevation of circulating immune subpopulations was accompanied by cell accumulation with lymphoid hyperplasia but a conserved distribution of B lymphocytes in lymphoid organs of chronically infected pigs.

Glaucomatous damage patterns by short-wavelength automated perimetry (SWAP) in glaucoma suspects.

PURPOSE: To determine the glaucomatous visual field damage patterns by short-wavelength automated perimetry (SWAP) in glaucoma suspects, and to compare the frequency of diffuse visual field losses and localized defects. METHODS: 157 eyes of 157 ocular hypertensive subjects who met the selection criteria (intraocular pressure greater than 21 mm Hg and normal standard visual fields) were studied. SWAP was done with a modified Humphrey Field Analyzer. Total (TD) and Pattern Deviation (PD) probability maps were calculated for SWAP. The frequency of abnormlities in the TD and PD were determined, analyzing the visual field loss components. RESULTS: The involvement of the test points was more frequent on the TD plots than on the PD plots for all levels of defects (p< 0.001). The glaucomatous defects also showed certain topographical distribution. CONCLUSIONS: A diffuse sensitivity component of visual field loss was found at all SWAP defect depths in glaucoma suspects.

Inhibition of African swine fever infection in the presence of immune sera in vivo and in vitro.

In assay cultures, sera from African swine fever convalescent pigs inhibited infection by homologous African swine fever virus. The infection-inhibition capacity did not correspond with the virus-neutralizing capacity. The serum did not prevent infection by heterologous virulent viruses. Sera from pigs challenge inoculated with the homologous virulent virus and later with a heterologous virulent virus inhibited the infection by different heterologous virulent viruses. These sera did not interfere with the infection by pseudorabies virus. The specificity of the reaction indicated that the infection inhibition was caused by antibody.

Neutralization of African swine fever virus by sera from African swine fever-resistant pigs.

Sera from African swine fever-resistant pigs with infection-inhibitory activity decreased virus replication in infected porcine buffy coat cultures. This same effect was observed even after virus was adsorbed. The infection-inhibition was not reversed by removing the immune serum from the assay cultures. Reduction of African swine fever virus replication by immune sera was demonstrated by fluorescent focus assay on MS cell line cultures. Virus-neutralization tests showed a persistent fraction of non-neutralized virus, which was not demonstrable by infection-inhibition tests. One hypothesis for explaining this difference is proposed.

Lymphocyte function and cell-mediated immunity in pigs with experimentally induced African swine fever.

Twenty-five pigs inoculated with African Swine fever virus were studied for the development of changes in lymphocyte numbers and function. The results indicated that lymphopenia and decreased percentage of circulating T-lymphocytes occurred as early as 7 days after the pigs were inoculated. These were accompanied by depressed lymphocyte function, as measured by mitogen- or antigen-induced blastogenesis. There were proportionately greater decreases in T-lymphocyte numbers and function than were found for B-lymphocytes. Studies of phagocytic cell function revealed decreased phagocytic function for peripheral blood monocytes and unchanged (normal) neutrophil function. Depressed T-lymphocyte function occurred in pigs with acute and subacute infections, indicating depression of cellular immune function.

A survey of bovine, bubaline and swine sarcocystosis in the Philippines.

In a survey conducted from January to December, 1994, muscle tissues in 12 out of 22 slaughtered carabaos ages 8-17 years old and obtained from the Food Terminal Inc, Abbatoir in Laguna showed numerous white and creamy elliptic-shaped soft bodied macrocysts in the throat muscles. Microscopic examination of the throat and cardiac muscle tissues revealed the presence of fusiform-shaped microcysts. Our observations are consistent with previous reports incriminating Sarcocystis fusiformis as the most important etiologic agent of bubaline sarcocystosis in the country. In a survey of bovine sarcocystosis in muscle tissues of imported Australian cattle (Brahman Breed) and native cattle obtained from various slaughter houses in Manila and suburbs, prevalence rates of 17% (98/577) and 3% (1/31) were noted, respectively. Sarcocysts were predominant in skeletal muscles and to a lesser extent in cardiac, esophageal and diaphragm muscle tissues. Light microscopic examination of sarcocysts morphology suggests Sarcocystis cruzi (= Sarcocystis bovis), and Sarcocystis hominis (= Sarcocystis bovihominis) or Sarcocystis hirsuta (= Sarcocystis bovifelis) as the likely etiologic agents of bovine sarcocystosis in the country. Of the 225 swines examined, only muscle tissues from a 6-month old swine revealed very young sarcocysts (= metrocytes). A review of available documented studies on sarcocystosis suggests that to date, our findings may represent the first data on the prevalence of bovine and swine sarcocystosis in the Philippines.

[Ambulatory arterial pressure and left ventricular hypertrophy in untreated hypertensive patients]. / Presión arterial ambulatoria e hipertrofia ventricular izquierda en pacientes hipertensos no tratados.

BACKGROUND: The study was designed to evaluate blood pressure (BP) values related to left ventricular hypertrophy (LVH) in a group of never treated middle-aged hypertensive subjects. PATIENTS AND METHOD: Non-invasive ambulatory blood pressure monitoring (ABPM) and echocardiography were performed in 149 hypertensive patients (25-50 years old) with diastolic blood pressure (DBP) 90-114 mmHg. LVH was considered when left ventricular mass (LVM) was > 134 g/m2 in males and > 110 g/m2 in females. RESULTS: 43% of patients had LVH. Patients with LVH had higher clinic and ambulatory BP values. The greatest differences were in mean 24-h SBP (p = 0.001) and in 24-h DBP (p = 0.006). With respect to LVH, there were no differences between dippers and non-dippers, males or females, and circadian or BP variability. LVM was positively correlated with clinical DBP (p = 0.24), 24 h SBP (p = 0.41), pulse pressure (PP) (p = 0.36) and absolute BP variability (p = 0.23). Multiple regression analysis confirmed that 24-h SBP and sex where positively associated with LVH independent of others factors. The existence of 24-h SBP > 150 mmHg dramatically increased the risk of LVH (odds ratio [OR] = 9.2; CI 95%: 2.8-29.3; p = 0.002). CONCLUSIONS: The present study indicates that in never treated middle-aged essential hypertensive patients the principal factor related to the presence of LVH is the value of systolic blood pressure throughout a 24-h period.

[Dysfunction of a TIPS (transjugular intrahepatic porto-systemic shunt) and chylous ascites]. / Disfunción de TIPS (transjugular intrahepatic porto systemic shunt) y ascitis quilosa.

We reported a 66 year old woman diagnosed of cirrhosis secondary to VHC. A TIPS (transjugular intrahepatic portosystemic shunt) placement was used for the treatment of recurrent variceal hemorrhage and, a chyloperitoneum with hepatorenal syndrome developed after shunt occlusion. We discuss the pathological processes that might be responsible and the poor prognosis of this no reported complication.

[Neuroretinal rim width in normal, hypertensive and glaucomatous subjects]. / Grosor del anillo neurorretiniano en sujetos normales, hipertensos y glaucomatosos.

PURPOSE: To determine width and shape of neuro-retinal rim in normal hypertensive subjects and patients with glaucomatous damage. MATERIAL AND METHOD: Patients underwent a perimetry and a photographic retinal nerve fiber evaluation. Patients were divided in three groups: normal subjects (n=34), ocular hypertension subjects (n=38) and glaucoma patients (n=34). Neuro-retinal rim was measured using 40 degrees stereoscopic photographs with center in the optic nerve head based on a biomorphometry technique. RESULTS: In normal subjects neuro-retinal rim appeared wider in the lower pole, followed by the upper, nasal and temporal aspects. Optic nerve fiber layer showed a decreased thickness in hypertensive and glaucoma patients, particularly in sectors of the temporal aspect of the optic nerve (p<0.05). CONCLUSIONS: A Planimetry study of the optic nerve is able to detect alterations in normal neuro-retinal rim configuration and can as well detect thinning of the rim, particularly in temporal, upper and lower areas.

[Early glaucomatous changes in neuroretinal rim shape]. / Cambios glaucomatosos precoces en la morfología del anillo neurorretiniano.

PURPOSE: To assess the differences in neuroretinal rim shape in ocular hypertensive patients (normal white-white automated perimetry) with and without perimetric injury in the short wave length automated perimetry (blue-yellow). MATERIAL AND METHODS: 72 eyes from 72 hypertensive ocular patients with normal achromatic automated perimetry examination were included. Forty eyes had normal short wave length automated perimetries while 32 subjects presented an abnormal condition. The neuroretinal rim morphology was quantified by means of a planimetric study from the papillary images obtained with confocal laser scanning. RESULTS: The subjects with abnormal blue-yellow perimetry showed a decrease in the neuroretinal rim area in the inferior and temporal positions. The differences were significant (p<0.05) at the 9 o'clock position (below the middle line) and almost significant (p<0.10) at the 10 o'clock position. CONCLUSIONS: There are differences in the neuroretinal rim shape in ocular hypertensive subjects with normal achromatic perimetry according to whether there are abnormalities in the blue-yellow perimetry.

[Experimental comparative study of the anti-inflammatory effectiveness of pranoprofen]. / Estudio comparativo experimental de la capacidad antiiflamatoria del pranoprofeno.

PURPOSE: To study the antiinflammatory capacity of topical pranoprofen in comparison with other ophthalmological nonsteroidal antiinflammatory drugs (diclofenac and flurbiprofen) in albino rabbits. METHODS: We have produced an endotoxin-induced uveitis by intravitreal injection of 10 ng of Salmonella typhimurium endotoxin. We have used 48 albino rabbits (4 groups of 12 animals each), first group were control group (intravitreal saline solution), which were treated unilaterally every two hours with 2 drops of: Group II, pranoprofen (1 mg/ml). Group III, diclofenac (0.2 mg/ml). Group IV, flurbiprofen (0.3 mg/ml). We determined clinical signs of inflammation and protein concentration in the aqueous humor. The rabbits were sacrificed 24 hours after the endotoxin administration. RESULTS: In all treated groups we observed a significant reduction (p<0.05) in all studied parameter as compared with control group, except for ciliar hyperemia. Different treatment groups did not show differences. CONCLUSION: The antiinflammatory capacity of pranoprofen is comparable to other NSAIDs derived from propionic acid such as flurbiprofen, obtaining a good control of endotoxin-induced uveitis.

[Inhibitory effect of nicardipine on fibroblast proliferation mechanisms]. / Efecto inhibitorio del nicardipino sobre los mecanismos de proliferación fibroblásticos.

PURPOSE: To assess the effect of nicardipine (NCP) on fibroblast migration and proliferation, and its cellular toxicity. METHODS: In vitro wound repair was assessed in confluent fibroblast monolayer. Mechanical round wounds were performed in the monolayers and the cultures were incubated in fresh media plus NCP. The cell-free area was monitored after 0, 18, 24 and 48 hours. Groups of treatment: Group 1, Sham. Group 2, NCP 10(-4)M in the media. Group 3, NCP 7.5x10(-5)M. Group 4, NCP 5x10(-5)M. Group 5, NCP 2.5x10(-5)M. Group 6, NCP 10(-5)M. Group 7, NCP 10(-6)M. Group 8, NCP 10(-7)M. Group 9, NCP 10(-3)M. Each experiment consisted of three tests that were repeated four times. RESULTS: The fibroblast migration and proliferation was inhibited at 5x10(-5)M or higher doses. The proliferation after 48 hours with NCP 2.5x10(-5)M was statistically inferior to the control group and groups 7, 8, and 9. NCP 5x10(-5)M or higher doses showed cellular atypia and cell death. CONCLUSIONS: NCP effectively inhibits fibroblastic wound repair process at doses 2.5x10(-5)M and shows toxicity at doses over 5x10(-5)M.

[Selective ophthalmic artery fibrinolysis in acute central retinal artery occlusion]. / Fibrinolisis selectiva de arteria oftálmica en la oclusión aguda de la arteria central de la retina.

PURPOSE: To evaluate efficacy and reliability of local intra-arterial fibrinolysis (LIF) in Retinal Central Artery Occlusion (RCAO). MATERIAL AND METHOD: We have studied 12 patients with RCAO. Seven patients (group I) were treated with conventional therapy and 5 patients (group II) underwent treatment with urokinase via transcutaneous femoral catheter into the ophthalmic artery. Thereafter patients received heparin sulfate for 3 days. RESULTS: Mean follow up was 14 months and mean time from onset of symptoms to the beginning of therapy was 11 hours. One patient in group I showed improvement of visual acuity (from counting fingers to 0.1). In all patients in group II there was angiographic evidence of improved perfusion of retinal arteries and 4 patients (80%) showed improvement in visual acuity. The best results were obtained when LIF was performed before 10 hours after onset of symptoms. No complications were observed after the fibrinolysis treatment. CONCLUSION: LIF in ophtalmic arteries for the treatment of RCAO reduces dosage of fibrinolytic agents and becomes a safe and useful treatment during the first hours post RCAO.

[Clinical manifestations of Stenotrophomas (Xanthomonas) maltophilia infection]. / Espectro clínico de la infección por Stenotrophomonas (Xanthomonas) maltophilia.

OBJECTIVE: Stenotrophomonas maltophilia (SM) is a gram-negative bacillus whose incidence like nosocomial pathogen has been incremented in the last years, especially in immunocompromised patients, subjected to invasive procedures and those receiving broad-spectrum antimicrobial therapy. METHOD: We report 15 isolations of SM between 1994-1996. RESULTS: The criteria for SM infection were fulfilled by 9 patients (60%), and 6 patients (40%) were colonized. The mean age of the patient was 60 +/- 12 years. Major predisposing factors in infections included venous catheterization (100%), prior surgery (86%), residence in ICU (80%), prior antibiotic therapy (80%) and intubation (66%). The most common underlying disease were heart disease (60%), treatment with immunosuppressors and/or steroids (46%) and chronic lung disease (46%). Ten cases (66%) had polymicrobial culture. The mortality rate was 40%. Risk factors associated with fatal outcome included the following: chronic lung disease (p = 0.043), nasogastric catheterization (p = 0.01), urinary tract catheterization (p = 0.02), intubation (p = 0.04) and the presence of pneumonia or sepsis by SM (p = 0.02). The most active agents were colistina (100%), cotrimoxazol (71%) and ceftazidima (53%). The isolates were highly resistant to first and second-generation cephalosporins (100%) tetracyclines (86%), aztreonam (91%) and imipenem (71%). CONCLUSION: SM cause a wide range of clinical syndromes and is more likely to cause infection or colonization in patients who have underlying disease. Due to its inherent multiple-antimicrobial resistance, it would appear its potential as a nosocomial pathogen will continue to increase. Therapy of patients should include cotrimoxazole.

[Langerhans cell histiocytosis of lymph node]. / Histiocitosis de células de Langerhans de presentación ganglionar.

Langerhans cell Histiocytosis or Histiocytosis X encompasses the syndromes of Letterer-Siwe disease, Hand-Schuller-Christian disease and eosinophilic granuloma. The localized disease usually consisted of isolated bone involvement as osteolytic areas. The isolated lymph node disease is uncommon. A case study of eosinophilic granuloma of lymph node in a 27 years-old woman who underwent several recurrences as lymphadenitis is presented. This case is presented in light of the cytologic, histologic and immunohistochemical findings of node-based eosinophilic granuloma and the favorable prognosis of this localized form treated with steroids.