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Biomedical subjects

A Rodriguez

Publications and source records attributed to A Rodriguez.

At least 145 records · Page 8Linked to original sources

Low-dose cyclosporine therapy in the treatment of birdshot retinochoroidopathy.

INTRODUCTION: Birdshot retinochoroidopathy is an uncommon uveitic syndrome of presumed autoimmune etiology. Therapy with systemic and periocular steroids is of inconsistent efficacy, attendant with numerous potential long-term side effects. Steroid-sparing strategies with more specific agents such as cyclosporine (Cyclosporin A, CSA) have been suggested as the first line treatment for this disease. PATIENTS AND METHODS: The records of 19 patients (35 eyes) with the clinical diagnosis of birdshot retinochoroidopathy were examined. Age at onset ranged from 33 to 69 years (mean, 46.1 years) in nine men and ten women. The median follow-up from disease onset was 36 months. Eight patients were treated with low-dose (2.5-5 mg/kg daily) CSA alone, six required the addition of azathioprine (1.5-2 mg/kg daily), and six received no systemic immunosuppressive therapy. RESULTS: HLA-A29 was positive in 94% (16 of 17) of patients tested. Vitreous inflammation was controlled in 23 (88.5%) treated eyes, with fewer bouts of recurrent inflammation, and a corresponding improvement or stabilization of visual acuity in 20 (83.3%) eyes. In contrast, intraocular inflammation never was controlled fully in untreated eyes, and visual acuity decreased in six (54.5%) eyes by an average of 2.5 Snellen lines. Nephrotoxic side effects of low-dose CSA therapy were not observed, but hypertension developed in two patients. CONCLUSION: Although the definitive strategy for the management of birdshot retinochoroidopathy is unknown, control of intraocular inflammation with a favorable visual outcome, together with a lack of demonstrable CSA-associated nephrotoxicity and secondary side effects in these patients with birdshot retinochoroidopathy indicate that vision preservation is possible with low-dose CSA alone or in combination with other steroid-sparing immunosuppressive agents as an alternative to the long-term use of corticosteroids.

Adult

Posterior segment ocular manifestations in patients with HLA-B27-associated uveitis.

PURPOSE: To describe a series of patients with seronegative arthritic syndromes and HLA-B27-associated uveitis with severe, sight-threatening, posterior segment ocular manifestations. METHODS: The authors reviewed the records of 29 patients (17.4%) with posterior segment involvement from a cohort of 166 patients with HLA-B27-associated uveitis. The inclusion criteria included individuals with a positive HLA-B27 who had at least one of the following findings: (1) severe vitreous inflammation; (2) papillitis; (3) retinal vasculopathy; or (4) pars plana exudates. The study population comprised 13 men and 16 women with a mean age at onset of uveitis of 35.2 years. The average duration of the uveitis was 5.3 years, and the median follow-up time was 26 months. FINDINGS: Posterior segment involvement occurred in 34 eyes of the 29 patients. The most common findings included severe and diffuse vitritis in 93.1% of the patients and papillitis in 24 patients (82.7%). Retinal vasculitis occurred in seven patients (24.1%), and pars plana exudates were present in two patients (6.8%). Cystoid macular edema (37.9%) and epiretinal membrane (17.2%) were common causes of visual impairment. Systemic immunosuppressive therapy was required for control of inflammation in 32% of the patients. CONCLUSION: HLA-B27-associated uveitis may be related to severe, sight-threatening posterior segment manifestations in some patients; this is an under-recognized phenomenon. These patients may require the use of aggressive systemic immunosuppressive therapy to control inflammation and preserve vision.

Adolescent

Debrisoquin oxidation genotype and susceptibility to lung cancer.

The association between the polymorphism of the cytochrome P450 debrisoquin hydroxylase (CYP2D6) and lung cancer is controversial. Previous reports suggested a link between CYP2D6 phenotype and lung cancer, with poor metabolizers having reduced susceptibility. Nevertheless, negative findings have also been published. By using allele-specific amplification, we have studied the frequency of four CYP2D6 (wild type and mutant) alleles in 89 patients with histologically proved bronchogenic carcinoma and in 98 healthy volunteers. Our findings confirm that poor metabolizers are underpresented among patients with lung cancer because of a different genetic background. Our findings also reveal that the rare CYP2D6(C) mutant allele is sixfold more frequent among patients with lung cancer (p < 0.0005). This suggests that the CYP2D6(C) allele could be considered as an additional risk factor because carriers could have higher susceptibility to the development of lung cancer.

Adult

Circulating proteins and iron status in blood as indicators of the nutritional status of 10- to 12-year-old Bolivian boys.

The purpose of the present study was to evaluate the nutritional status of children based on anthropometric measurements, biochemical indicators of protein energy malnutrition as well as hematological variables. The subjects were 93 10- to 12-year-old Bolivian boys: 12 HAHSES, 28 HALSES, 36 LALSES, and 17 LALSES (see Introduction to this Supplement). The overall nutritional status of the boys was evaluated by anthropometric indicators (weight for age [W/A], height for age [H bd, and weight for height [W/H]). The biochemical indicators included proteins total, albumin, prealbumin, orosomucoid and protein C-reactive (for MPE) as well as hematocrit (Ht), hemoglobin (Hb), serum iron, serum ferritin, and transferrin saturation (TS). The prevalence of growth retardation of LSES boys at HA as well as at LA was found to be high when the 3rd percentile was used as the cutoff point. The corresponding prealbumin levels were found to be lower in LSES than in HSES boys at both altitudes. The study shows that LSES boys at both altitudes have significantly lower prealbumin levels than HSES boys. The socioeconomic factor seems to be more critical for the nutritional status of prepubertal boys than altitude. The study also shows that all the boys had hematological parameters within normal range. The HA boys of both SES had higher hemoglobin concentration and hematocrits than the LA boys, a fact that is explained by high-altitude hypoxia. The hematological data do not provide evidence of malnutrition among the boys.

Altitude

Hodgkin's disease with a mediastinal mass greater than 10 cm: results of four different treatment approaches.

BACKGROUND: Management of Hodgkin's disease (HD) and large mediastinal adenopathy (LMA) usually includes intensive chemotherapy (CT) with or without radiation therapy (XT) regardless of stage. PATIENTS AND METHODS: One hundred and eighteen evaluable patients received one of four treatment regimens: (1) 6 cycles of MOPP or similar CT and XT; (2) 2 of MOPP followed by XT; (3) 6 of CVPP/ABDIC (cyclophosphamide, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, decarbazine, prednisone, lomustine) followed by XT; or (4) 3 of NOVP (mitoxantrone, vincristine, vinblastine, procarbazine) and XT. XT doses included 30-40 Gy to areas of nodal involvement noted prior to therapy. RESULTS: Complete remission (CR) rates for groups 1, 2, 3, and 4 were 100%, 85%, 87%, and 96%. Respective 3-year freedom from progression (FFP) results were 88%, 66%, 82%, and 88%, and 3-year freedom from tumor mortality (FTM) results were 100%, 84%, 84%, and 100%. The presence of B symptoms and stage IV disease was correlated with lower CR and 3-year FFP rates but similar 3-year survival. CONCLUSIONS: Results of this study suggest that patients with stage I-III Hodgkin's disease and LMA greater than 10 cm treated with 3 NOVP and XT have results similar to those obtained for a similar group of patients treated with 2 to 6 MOPP or 6 CVPP/ABDIC and XT. NOVP has also been reported to produce limited toxicity in this trial and should be considered as an alternative to MOPP or doxorubicin-containing regimens in treatment of patients with early-staged disease and LMA greater than 10 cm.

Adolescent

Adynamic bone disease with negative aluminium staining in predialysis patients: prevalence and evolution after maintenance dialysis.

Aplastic bone disease (ABD) is a common form of renal osteodystrophy and is characterized by a defect in bone matrix formation and mineralization without an increase in osteoid thickness. The prevalence and pathogenesis of ABD in predialysis patients is largely unknown. We prospectively studied 92 unselected predialysis patients with a creatinine clearance < 10 ml/min/1.73 m2 and a mean age of 45 +/- 2 years (61 M, 31 F). None of the study patients had received any form of vitamin D therapy, and CaCO3 was the primary phosphate binder. Aplastic bone disease was observed in 30 (32%) patients. Stainable bone aluminium surface was < 3% in all ABD patients. Patients with ABD were older (52 +/- 3 versus 42 +/- 2 years; P < 0.01) and had reduced serum intact PTH compared to non-ABD patients (199 +/- 25 versus 561 +/- 87 pg/ml; P < 0.001). Patients with diabetes mellitus showed lower PTH values (179 +/- 31 versus 432 +/- 62 pg/ml; P < 0.001) and a lower incidence of advanced hyperparathyroidism bone lesions (16% versus 46%; P < 0.05) than non-diabetic patients. However, diabetes was not clearly associated with low bone turnover disease (56% in diabetics versus 41% in non-diabetics; P = 0.1). A second bone biopsy was obtained in eleven ABD patients after a period of 16.6 +/- 2.2 months on maintenance dialysis with a dialysate calcium of 7 mg/dl. Bone histology was unchanged in 10 patients, and one evolved to mild hyperparathyroidism. Trabecular bone volume did not change (22.7 +/- 1.7 versus 20.7 +/- 1.7%), and the stainable bone aluminium surface remained < 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Decrease in detectable complement receptor type 1 levels on erythrocytes from patients with psoriatic polyarthritis.

The complement receptor type 1 (CR1) levels on erythrocyte membranes from 23 patients with PsA was determined by using ELISA. Six patients had an axial form, the rest had peripheral arthritis (10 polyarthritis and seven oligoarthritis). A significant decrease in levels of this receptor was found in patients with polyarthritis compared with healthy controls. Non-significant differences were found when comparing the other two groups of patients with the controls, although the mean values of CR1 were lower in the patients' group. We also found an inverse correlation between CR1 levels and articular index, but not with ESR, CRP or disease duration. No differences in the CR1 density were obtained for HLA-B27 positive and HLA-B27 negative patients.

Adult

Antigenic analysis of rabies-virus isolates from Latin America and the Caribbean.

A total of 288 rabies-virus samples from 17 Latin American and Caribbean countries were reacted with an array of monoclonal antibodies. Identification of eight distinct antigenic variants among these samples permitted epidemiologic studies of the geographic distribution of different concentrations of rabies in the region and of the animal species serving as maintenance sources for rabies within a concentrated area. Two variants were broadly distributed and associated with enzootic disease in dogs and vampire bats. All isolates from cases of human rabies contained one of these two variants. Two variants had a limited distribution: an outbreak in Brazil, primarily affecting dogs and believed to be maintained by dog-to-dog transmission, and nine cases of rabies in cattle in Venezuela, animal reservoir unknown. A reservoir of rabies in insectivorous bats was identified and the associated variant was found in a rabid domestic cat. The remaining three rabies variants were found in single isolates only, but due to inference from antigenic-typing data from North American samples, were believed to be maintained by reservoirs of rabies in hoary bats, foxes, and skunks.

Animals

Cell density can affect cholesteryl ester accumulation in the human THP-1 macrophage.

Esterified cholesterol (EC) accumulation was induced in THP-1 macrophages after exposure to acetylated LDL (acLDL), and the extent of accumulation was dependent on cell density. EC mass was 5-fold greater in cells plated at 1.0 x 10(6) cells/35 mm dish compared to cells plated at density 4.0 x 10(6) cells/dish. In addition, [14C]oleate incorporation into EC also increased with decreasing cell number, with 4-fold greater incorporation (6 h: 177 +/- 0.014 vs. 45 +/- 0.001 pmol/mg cell protein, P < 0.001; 24 h: 515 +/- 0.037 vs. 120 +/- 0.012 pmol/mg, P < 0.001) in cells plated less densely compared to cells plated at a higher density. The rate of 125I-labeled acLDL degradation was about 2-fold greater in cells plated at the lower density (105 vs. 60 ng/h per mg cell protein). Northern analysis showed a 2-fold reduction in the expression of human scavenger receptor mRNA in density plated cells, and immunoprecipitation also demonstrated a 2-fold decrease in scavenger receptor protein. Conditioned media did not differentially affect EC formation at either cell density. Fatty acid supplementation increased EC formation and the proportion of esterified sterol content only in cell plated at the higher density. The fatty acid effect was also seen when cells were exposed to beta-VLDL, which induced comparable levels of EC accumulation by non-scavenger receptor-mediated processes in densely plated cells. Foam cell formation in THP-1 macrophages may depend on cell density, which appears to affect both scavenger and non-scavenger receptor activity.

Acetylation

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.

Animals

Multicentre evaluation of the Boehringer Mannheim Hitachi 911 system for homogeneous immunoassays.

A multicentre evaluation of the new analyser, Hitachi 911, is reported for three different classes of homogeneous immunoassays (latex assays, immunoprecipitation assays, and CEDIA assays). The evaluation protocol follows ECCLS, IFCC and NCCLS guidelines. Using patient samples and commercial controls, within run and between run coefficients of variation were less than 3% in most cases, but as high as 9.7% for some CEDIA and latex assays. All the assays were linear, either in the reference or the therapeutic range of the analytes. No interference by haemolysis, lipaemia or icterus was observed. The methods were compared with other commercial methods. Coefficients of correlation were higher than 0.94 for all the methods. However, there were differences of slope and intercept for rheumatoid factor, apolipoprotein A-I and apolipoprotein B. On the Hitachi 911, all of the eight methods give precise and accurate results, and compare well with other established methods on immunoassay dedicated analysers. The discrepancies observed could be ascribed to current problems of immunoassay standardization.

Chemistry, Clinical

Obesity.

Although obesity and trauma both are common in the general population, discussion of the care of the critically injured obese patient has been relatively absent. Obesity is associated with significant clinical and occult multisystem disease. Because host factors are key determinants of post-traumatic course and outcome, obesity appears to be a marker of high risk. Obesity should be considered with age, pregnancy, cardiopulmonary disease, and substance abuse as a host factor that has significant post-traumatic ramifications. Only by employing a comprehensive, multidisciplinary approach to the critical care management of such patients will post-traumatic complications be prevented and treated effectively.

Humans

Flail chest as a marker for significant injuries.

The records of 92 patients with flail chest injury treated at a Level I trauma center were analyzed retrospectively. Associated intrathoracic injuries included pulmonary contusion (46 percent) and pneumothorax or hemothorax, or both (70 percent). The incidence of great vessel, tracheobronchial and diaphragmatic injuries was no different from that of a control population with simple rib fractures. Adult respiratory distress syndrome developed in 27 percent of patients with flail chest; 69 percent of all patients required ventilation (mean duration, 22 days). Mean length of hospital stay was 24 days. The mortality rate was 33 percent. We conclude that flail chest serves as a marker of significant intrathoracic injury, highly associated with pulmonary contusion, but even more so with pneumothorax or hemothorax. Flail chest does not seem to be a marker for great vessel, tracheobronchial, or diaphragmatic injuries. The majority of patients (more than two-thirds) will require mechanical ventilation for prolonged periods. Of paramount importance is the recognition of flail chest as a marker of high kinetic energy absorption, resulting in life-threatening thoracic as well as nonthoracic injuries.

Adult

Exacerbation of murine herpes simplex virus-mediated stromal keratitis by Th2 type T cells.

Corneal infection of susceptible mice with HSV-1 causes herpetic stromal keratitis (HSK), which serves as a model of human HSK. To study the properties of the T lymphocytes involved in HSK, susceptible mice were immunized with the synthetic peptide corresponding to the amino terminal of HSV-1-associated glycoprotein D (gD 5-23). A CD4+ long-term T cell line and a clone bearing V beta 8.2 TCR were derived from peptide-primed lymph node cells. These T cells recognize gD 5-23 peptide in the context of I-Ed and require CD4 and LFA-1 for Ag-specific proliferation. Significantly, a truncated peptide gD 15-23 induced vigorous proliferation, indicating that these 9 amino acids constitute an epitope recognized by these T cells. The gD-specific T cells produced IL-4 and used it as the autocrine growth factor and hence belong to the Th2 subtype. Adoptive transfer of gD-specific Th2 cells into susceptible mice increased both the onset and severity of HSK after corneal HSV-1 infection. Injection of gD-specific Th2 cells without HSV-1 infection failed to cause eye damage. In addition, an irrelevant Ag-specific Th2 clone failed to induce similar tissue damage when the corresponding Ag was applied to the eye. These data indicate that the T cell-mediated exacerbation of HSK in these studies is dependent on the specific recognition of gD after corneal HSV-1 infection. Finally, gD-specific Th2 cell transfer also rendered HSK-resistant mice susceptible for HSK, suggesting that the freedom from HSK in resistant mice may primarily be due to their inability to produce the pathogenic Th2 cells. The data collectively implicate an important role for Th2 cells in the induction of HSV-mediated keratitis in mice.

Amino Acid Sequence

Early decrease in minimal luminal diameter after successful percutaneous transluminal coronary angioplasty predicts late restenosis.

Eighty-eight patients underwent serial coronary arteriography before, immediately after, 24 hours after and 7 +/- 2 months after successful percutaneous transluminal coronary angioplasty (PTCA) of 102 lesions. Severity of coronary obstruction was measured using quantitative digital angiography. Three groups of lesions were defined when comparing angiograms recorded immediately after and 24 hours after PTCA: group I--lesions with either no change or < or = 10% increase in arterial diameter stenosis after PTCA (n = 71); group II--lesions with > 10% increase in diameter stenosis after PTCA (n = 19); and group III--patients with total occlusion (n = 12). There were no significant differences in the severity of stenosis before or immediately after PTCA among the 3 groups of lesions. Twenty-four hours after PTCA the diameter stenosis was 14.2 +/- 6.3% in group I, 34.7 +/- 8.1% in group II and 100 in group III (p < 0.0001). At 7.1 +/- 2 months after PTCA the diameter stenosis was 21.2 +/- 16.8% in group I, 61.3 +/- 1.1% in group II, and 98.5 +/- 1.3% in group III (p < 0.0001). Restenosis (> or = 50% stenosis diameter) at follow-up per lesion was significantly greater in group II than in group I (73.6 vs 9.8%) (p < 0.0001). Thus, early angiographic study after successful PTCA stratifies lesions into angiographic subsets with low (group I) and high (group II) risk of coronary restenosis.

Adult

The polymerase chain reaction for the detection of Borrelia burgdorferi in human body fluids.

OBJECTIVE: To analyze clinical fluids for the presence of Borrelia burgdorferi DNA using the polymerase chain reaction (PCR). METHODS: We utilized a modified, nested PCR to detect the presence of Borrelia DNA in 99 samples of serum, urine, cerebrospinal fluid (CSF), or synovial fluid obtained from 44 patients with various stages of Lyme disease and 47 control subjects. Primer specificity was corroborated by examining 2 DNA data banks, testing against DNA from other organisms, and confirming results with a second set of nested primers. RESULTS: Nested PCR was capable of detecting DNA from fewer than 10 organisms in 1 ml of fluid. The specificity of this technique was 96.4%, with a sensitivity of 76.7%. Although the specificity was uniformly high, the sensitivity was dependent upon the body fluid being tested: CSF 100%, urine 100%, synovial fluid 80%, and serum 59%. The rate of false-positive results was 3.6%. CONCLUSION: These data demonstrate the potential utility of PCR in confirming the clinical diagnosis of Lyme disease as well as providing insight into the pathogenesis of various stages of this disorder.

Base Sequence