Infestation of rural houses by Triatoma infestans (Hemiptera: Reduviidae) in southern area of Gran Chaco in Argentina.

The impact of control activities against Triatoma infestans (Klug) (Hemiptera: Reduviidae) in South America has a marked contrast within and outside the Gran Chaco region. Development of a geographic information system, as part of an improvement in control program activities, allowed analysis of the spatial pattern of house infestations by T. infestans before and after house spraying with deltamethrin in the San Martin Department (an arid Chaco region of central Argentina). The overall peridomestic infestation index decreased from 48.2 to 28.2% after insecticide application. House infestation was spatially clustered in regions with low or high infestation levels that were located east and southwest of the department, respectively. This pattern was detected both before and after the insecticide application. Three environmental variables calculated from a temporal series of MODIS imagery (average of night temperature, maximum of day temperature, and temporal variation of vegetation index) were capable of correctly discriminating 96% of the places belonging to either high or low house infestation observed after the insecticide application.

Diazepam administration prevents testosterone decrease and lipofuscin accumulation in testis of mouse exposed to chronic noise stress.

Lipofuscin is an autofluorescent and undegradable material, which accumulates in tissues during ageing and under different types of stress. Among these, oxidative stress represents a major trigger for lipofuscin formation. However, prolonged noise exposure is also an effective stressful stimuli. Diazepam may inhibit lipofuscinogenesis in liver and prevent the noise-induced reduction of the steroidogenesis in the adrenal gland. The aim of the study was to ascertain whether chronic noise exposure causes lipofuscin accumulation in mouse testis, and to evaluate the effects of diazepam administration. Eight-week old mice were either exposed for 6 weeks (6 h day(-1)) to white-noise (group A), or received diazepam (3 mg kg(-1), i.p.) before noise exposures (group B), while a further group was used as control (group C). Light fluorescence and transmission electron microscopy revealed lipofuscin in large amounts in the Leydig cells in mice of group A, which concomitantly had low serum testosterone levels; pre-treatment with diazepam occluded both effects. The present study indicates that: (i) chronic noise exposure causes lipofuscin accumulation at the level of the Leydig cells and a decrease in testosterone; (ii) all these effects are suppressed by pre-treatment with diazepam. As the Leydig cells represent the only cellular type of the interstitial testicular tissue having peripheral benzodiazepine receptors, these results could be explained by the capacity of the peripheral benzodiazepine receptors to prevent reactive oxygen species damage and to increase the resistance of these cells to oxidative stress.

Inflammatory mediators and eosinophilia in atopic and non-atopic patients with nasal polyposis.

Nasal polyps are characterized by eosinophilic infiltration and presence of inflammatory mediators, such as total IgE, eosinophil cationic protein (ECP) and cytokines. The role of atopy in nasal polyp pathogenesis is still unclear. Therefore, we evaluated serum IgE levels, nasal mucus concentrations of ECP and cytokines and the number of infiltrating eosinophils in nasal tissue of polyps from atopic and non-atopic patients. Samples were obtained from a randomized population of 31 patients with nasal polyposis having endonasal sinus surgery and of 13 control subjects undergone corrective surgery of the nasal septum. On the basis of medical history of allergy, positive skin-prick tests and total IgE levels, patients with polyposis were divided in atopic (n = 13) and non-atopic (n = 18) patients. We determined levels of IgE in blood, ECP and cytokines (IL-4, IL-6, IL-8, IFN-gamma and IL-2) in nasal mucus, and number of infiltrating eosinophils in nasal tissue. The concentrations of total IgE, ECP, IL-4 and IL-8 and eosinophilia were significantly higher in all patients with nasal polyps compared with controls. Inside, all patients with nasal polyposis showed lower levels of IL-6, IFN-gamma and IL-2 compared with controls. The atopic patients showed significant differences when compared with non-atopic patients for the higher concentrations of total IgE (698.80+/-322.24 vs. 279.63+/-234.11; P < 0.0001) and IL-8 (1437.2 pg/ml+/-1250.7 vs. 605.5 pg/ml+/-481.1; P < 0.015). These findings suggest that inflammation still remains the major factor in the etiology of nasal polyposis and show different levels of inflammatory mediators into atopic and non-atopic patients.

Ankyloglossia: a morphofunctional investigation in children.

OBJECTIVES: To provide diagnostic criteria for ankyloglossia in children by anatomical measurements; to investigate the correlation between severity of ankyloglossia and a series of morphofunctional findings; to evaluate the potential mismatch between a clinical suspect of ankyloglossia and the authentic anatomical diagnosis. DESIGN: Two different techniques of anatomical measurements and a clinical evaluation of a series of morphofunctional findings were performed. SUBJECTS AND METHODS: In 200 children referred for evaluation and treatment of tongue-tie, the length of the frenulum and the interincisal distance were measured in maximum opening of the mouth and with the tip of the tongue touching the palatal papilla. Occlusion, type of bite, tongue resting position, swallowing mechanism, oral floor mobility, frenulum insertion modality and speech were investigated. Any correlation between these morphofunctional findings and anatomical measures was investigated. RESULTS: Children with a frenulum length more than 2 cm and an interincisal distance of more than 2.3 cm were normal. In both measurements, significant correlations among mean values and other variables were observed. Moreover, three levels -- mild, moderate and severe -- of ankyloglossia were assessed. CONCLUSIONS: Length of frenulum and interincisal distance allow an assessment of severity of ankyloglossia in children. Ankyloglossia was not associated with infantile swallowing.

Distribution of 3-nitrotyrosine in the nasal polyps of atopic patients.

OBJECTIVE: To investigate whether formation of nitrotyrosine in the nasal polyps of atopic patients occurs. STUDY DESIGN: A nonrandomized, retrospective, controlled qualitative and quantitative study. METHODS: Nasal polyp tissue samples were acquired from 12 atopic patients. Control fragments of nasal mucosa were taken from 10 patients undergoing corrective surgery of the nasal septum. For routine histologic examinations, hematoxylin-eosin staining was used. Low-magnification microscopy was designed to yield pathologic characteristics and high magnification to quantify the number of eosinophils in the subepithelial connective tissue. Presence of nitrotyrosine was assessed by immunohistochemical method. RESULTS: Hematoxylin-eosin staining revealed presence of numerous eosinophils in the epithelium and in the subepithelial connective tissue. All polyps were characterized by epithelial damage. Nitrotyrosine was present in the eosinophils, in the ciliated cell, and in cells of the damaged epithelium. Goblet cells, glands, and vessels were found to be negative. No significant differences concerning the localization of nitrotyrosine were recognized among the examined nasal polyps. CONCLUSIONS: Nitrotyrosine immunohistochemical staining in nasal-polyp tissues suggested the existence of progressive epithelium injury caused by peroxynitrite. Consequences of peroxynitrite formation in eosinophils remain to be precisely established. The lack of nitrotyrosine in glands and blood vessels indicated that peroxynitrite does not have a significant role in the vascular and glandular dysfunction of nasal polyps.

Cytokine secretion in nasal mucus of normal subjects and patients with allergic rhinitis.

Allergic rhinitis is regulated by the local production and release of several cytokines. The levels of Th2 cytokines IL-4, IL-6, IL-10 and the Th1 cytokine IFN-gamma were studied in nasal mucus from 30 subjects with allergic rhinitis and 45 non-atopic healthy controls. In this study a sampling technique for collecting nasal mucus, well tolerated by the subjects and with a minimal stimulation of the mucosa, was performed. The cytokine concentrations in nasal mucus samples were detected and quantitated by a new paramagnetic particle-based immunofluorescent assay system more sensitive than the conventional ELISA techniques. The new technique showed reliable values of the measured parameters. The nasal mucus from allergic patients contained significantly higher concentrations of IL-4 (25.5 +/- 3.6 pg/ml; P < 0.001) and IL-10 (1300 +/- 190 pg/ml; P < 0.05) compared to the nasal mucus from control subjects (15.2 +/- 2.3 and 532 +/- 28 pg/ml, respectively, for IL-4 and IL-10). No significant modification in IFN-gamma levels of allergic patients was found when compared to control group (respectively, 19.9 +/- 3.3 vs. 25.7 +/- 5.1 pg/ml; P > 0.05). Moreover, the allergic patients showed lower levels of IL-6 concentrations in the nasal mucus compared to control subjects (64.8 +/- 9.1 vs. 129.0 +/- 18.1 pg/ml; P = 0.0099). These data can be interpreted by the hypothesis that in response to environmental allergens there is a preferential Th2 polarity by activated CD4+ T cells and that the cytokines IL-6 and IL-10 have, respectively, an important anti-inflammatory and counterregulatory action in the pathogenesis of allergic rhinitis.

The targets of nephritogenic antibodies in systemic autoimmune disorders.

In situ formation of immune complexes is a well recognized mechanism of renal injury in systemic autoimmune disorders. The identification of intrinsic renal antigens that are targets of nephritogenic antibodies is a field of active investigation. Recently, two proteins expressed in the kidney have been characterized as renal antigens. Alpha-actinin, an actin-binding protein localized in glomerular podocytes, is the major target of nephritogenic anti-DNA antibodies. Alpha-enolase, a glycolytic enzyme, is a target of nephritogenic anti-DNA and non-anti-DNA antibodies.

Modulation of beta2 integrin phenotype, adhesion, chemotaxis, and oxidative burst of neutrophils by cyclosporine.

Cyclosporine (CsA) is an immunosuppressive drug widely used to prevent allograft rejection, but its action on neutrophil function is not well known. Neutrophils play an important role in tissue damage during allograft rejection; chemotactic recruitment, adhesion to endothelial cells and oxidative burst of neutrophils are early events during allograft rejection. The aim of this work was to evaluate the effect of CsA on beta2 integrins' surface expression, adhesion to human umbilical endothelial cells (HUVECs), chemotaxis and oxidative burst by neutrophils. For any neutrophil function studied, data obtained from activated neutrophils exposed to CsA were compared with those derived from untreated controls. Results show that CsA does not block neutrophil chemotaxis and does not reduce surface expression of CD11 complex and HUVECs' adhesion at all concentrations tested (15, 100 and 500 ng/mL) and at incubation times of 1, 2 and 4 h as compared to controls. On the other hand, the drug affects significantly the CD18 phenotype after two hours of treatment at the maximum concentration (500 ng/mL) (P < 0.05; ANOVA) and the oxidative burst after four hours (P < 0.01; ANOVA). This study provides evidence that in addition to the well-known CsA effects on lymphocyte functions, the drug affects some neutrophil functions with dose- and time-dependent modalities.

Infection with Burkholderia cepacia in cystic fibrosis: outcome following lung transplantation.

As a result of concern over excessive mortality after lung transplantation, many transplant programs refuse to accept cystic fibrosis (CF) patients infected with Burkholderia cepacia. As a significant proportion of patients with CF in our community are infected with this organism, we have continued to provide lung transplantation as an option. A retrospective review was conducted of medical records of all patients with CF transplanted between March 1988 and September 1996. Fifty-six transplant procedures were performed in 53 recipients with CF between March 1988 and September 1996. Twenty-eight had B. cepacia isolated pretransplant and 25 remaining positive post-transplant. Of the 53 recipients, 19 have died (15 of 28 [54%] B. cepacia positive and 4 of 25 [16%] B. cepacia negative). B. cepacia was responsible for or involved in 14 deaths. Nine of the deaths occurred in the first 3 mo post-transplantation. One-year survival was 67% for B. cepacia positive patients and 92% for B. cepacia negative patients. Recent modifications in antimicrobial and immunosuppressive therapy since 1995 have resulted in no deaths early post-transplant in the last five patients transplanted. We conclude that early mortality in patients with CF infected with B. cepacia is significantly higher than in those not infected with B. cepacia. Modifications in post-transplant medical therapy may improve outcome.

Surface expression of a glycolytic enzyme, alpha-enolase, recognized by autoantibodies in connective tissue disorders.

In systemic autoimmune diseases, autoantibodies specific for alpha-enolase are detected more frequently in patients with active renal involvement. To analyze the properties of anti-alpha-enolase antibodies and the distribution of the enzyme in the cell, mouse monoclonal and polyclonal antibodies were obtained from mice immunized with a glutathione-S-transferase-alpha-enolase fusion protein. Anti-alpha-enolase antibodies were purified from patient sera on enolase from human kidney. Using these antibodies, the distribution of alpha-enolase in the cell was analyzed in subcellular fractions and in the cell membrane by flow cytometry and immunoprecipitation. Plasminogen binding was studied by an immunoenzymatic assay. We observed that alpha-enolase was present in the cytosol and membrane fractions obtained from kidney and U937 cells. By flow cytometry, mouse polyclonal anti-enolase antibodies, one monoclonal and 7/9 human anti-enolase antibodies bound the membrane of U937 cells. One monoclonal antibody and mouse polyclonal anti-enolase antibodies immunoprecipitated a 48-kDa molecule from surface-labeled U937 cells and this molecule was recognized by rabbit anti-enolase antibodies. Both immunization-induced antibodies and 7/9 autoantibodies from patient sera inhibited the binding of plasminogen to alpha-enolase. The results show that alpha-enolase, an autoantigen in connective tissue diseases, is a cytoplasmic enzyme which is also expressed on the cell membrane, with which it is strongly associated. Anti-alpha-enolase autoantibodies isolated from patient sera recognize the membrane-associated form of the enzyme and/or interfere with its receptor function, thus inhibiting the binding of plasminogen. Autoantibodies specific for alpha-enolase could play a pathogenic role, either by a cytopathic effect or by interfering with membrane fibrinolytic activity.

Pharmacokinetic profile and variability of cyclosporine versus neoral in patients with cystic fibrosis after lung transplantation.

Various factors may influence bioavailability and blood concentrations of cyclosporine, a problem that may be compounded by diseases such as cystic fibrosis in which impaired absorption through the gastrointestinal tract is common. Neoral, a microemulsion formulation of cyclosporine, has improved bioavailability and more stable blood concentrations than earlier formulations. We conducted a prospective, open, crossover study to examine whether these findings held true in 12 clinically stable patients with cystic fibrosis who had undergone lung transplantation at least 6 months earlier. In the first arm, patients continued their usual dosage of cyclosporine twice/day. In the second arm they received Neoral for at least 1 week before having blood studies. For each arm whole blood trough concentrations were drawn for 7-10 successive days, together with a pharmacokinetic study with concentrations drawn at times zero, 1, 2, 3, 4, 6, 12, and 24 hours. Variance was assessed from morning concentrations. Area under the curve from zero to 12 hours (AUC12), maximum concentration (Cmax), and time to Cmax (Tmax) were calculated for each arm. Eleven subjects completed the protocol. The daily variance for Neoral was significantly less than for cyclosporine (p=0.04). The AUC12 for Neoral and cyclosporine were 4164+/-1467 and 5318+/-1670 microg x L/hour (p=0.09), respectively. Respective Cmax were 613+/-242 and 931 +/-458 microg/L (p=0.08) and relative Cmax and AUC12 were 1.91 and 1.47 (p<0.05). Thus Neoral had a superior pharmacokinetic profile and less day-to-day variability in patients with cystic fibrosis who had undergone lung transplantation.

Return to work after lung transplantation.

The social rehabilitation of lung transplant recipients becomes increasingly important as the results of lung transplantation improve. Although return-to-work (RTW) rates have been published for recipients of other organ transplants, no such data are available after lung transplantation. The purpose of this study was to determine what factors influence RTW after lung transplantation. Of 99 lung transplant recipients (43 single, 56 bilateral) surveyed from Denver, Colorado, (n = 49) and Toronto, Ontario, Canada (n = 50), 22% (n = 22) were employed, 38% (n = 38) were unemployed but medically able to work, 29% (n = 29) were medically disabled, and 10% (n = 10) had retired. The RTW rate for those medically able to work was 37% (22/60), and it was identical at each center (n = 11). Only Canadian lung transplant recipients (36%, 4/11) secured new jobs, whereas all Colorado lung transplant recipients returned to their previous employment (100%, 11/11). A stepwise discriminant analysis revealed that (1) pretransplantation employment, (2) a diagnosis of emphysema, cystic fibrosis, or primary pulmonary hypertension, (3) a self-report of being physically able to work, (4) greater functional improvement as measured by post-lung transplantation percent predicted forced vital capacity, and (5) post-lung transplantation 6-minute walk > 550 m positively influenced RTW. This analysis accurately profiled 82% of the employed and 76% of the unemployed recipients for an overall effectiveness of 79%. The findings of this study are that (1) a 37% employment rate for those physically able was comparable to other types of organ transplant recipients, (2) employment was not determined by the type of lung transplantation procedure (single or bilateral), and (3) social factors remain employment barriers for some recipients, but their absence did not guarantee a better employment rate.

Tacrolimus as rescue therapy for bronchiolitis obliterans syndrome.

BACKGROUND: Chronic lung allograft rejection manifested by sustained declines in lung function is the most common cause of late death after lung transplantation. Numerous strategies have shown variable results. We sought to evaluate the effect of FK506 (tacrolimus) on bronchiolitis obliterans syndrome (BOS) after lung transplantation. METHODS: A single-center open study was conducted of 15 patients whose treatment was converted to tacrolimus from cyclosporine. Of the 15, 12 patients had BOS characterized by sustained loses in lung function while receiving cyclosporine. Rate of decline of forced expiratory volume in 1 second (FEV1) for the 12 patients was calculated before and after administration of tacrolimus. Biochemical changes before and after conversion were compared for the entire group. RESULTS: Median monthly rate of decline in FEV1 was significantly reduced after administration of tacrolimus (5.3% vs 1.1%; p = 0.002). Forced vital capacity did not change significantly. No subjects experienced at least a 10% improvement in FEV1. At least a 10% further decline in FEV1 was noted in five subjects, and seven subjects had no change (i.e., within 10% of baseline). A minor nonsignificant increase in creatinine occurred after administration of tacrolimus. Blood cell count, electrolytes, and liver enzymes remained unchanged. The median change in fasting blood glucose was +0.7 mmol/L (p = 0.02). CONCLUSION: Although tacrolimus does not reverse changes in FEV1 with BOS, in this nonrandomized study it seemed to be associated with a decrease in the rate of decline in lung function and no significant sustained toxicity. Further studies are necessary to substantiate this observation.

Lack of left ventricular dysfunction associated with sustained exposure to hyperlipidemia following lung transplantation.

OBJECTIVES: Hyperlipidemia due to standard immunosuppressive agents occurs commonly following solid organ transplantation. A decision to treat hyperlipidemias would be based on the assumption that such disorders lead to accelerated atherogenesis and ultimately to cardiac dysfunction. We therefore sought to examine whether hyperlipidemias following lung transplantation were associated with a decline in left ventricular (LV) function. STUDY DESIGN: We retrospectively reviewed serial echocardiograms, radionucleotide angiograms (RNAs), and serum lipid levels following lung transplantation. Results of cardiac studies were defined as abnormal if a decline in LV grade occurred from the best result at any time postoperatively to the most recent study. PATIENTS: A total of 184 patients with transplants between November 1983 and June 1995 were reviewed. Eighty patients were excluded owing to incomplete data. One patient was excluded because of severe perioperative myocardial dysfunction. RESULTS: Approximately 80% of patients had elevated cholesterol levels and 60% had elevated low-density lipoprotein levels. Triglyceride levels were raised in 34% of patients while only 4% had an abnormal serum high-density lipoprotein level. More than 80% of patients had no evidence of LV abnormalities in either RNA or echocardiographic studies (group 1). One patient had a change in echocardiographic LV function but no change in grade of RNA (group 2). Twenty patients had a decline in grade based on RNA but no change in the echocardiogram (group 3). There were no patients with changes in both RNA and echocardiogram (group 4). All changes in LV function were from grade I to II. The mean period of follow-up exceeded 30 months for patients in groups 1 to 3. Follow-up data at 3, 4, and 5 years were available on 47, 23, and 12 patients, respectively. There were no differences between the proportions of subjects with normal and abnormal serum lipid levels in each group. CONCLUSIONS: In the initial 5 years after lung transplantation, dyslipidemias affect the majority of patients but are not associated with evidence of deteriorating LV function.

Status of lung transplant recipients surviving beyond five years.

BACKGROUND: Prolonged survival after lung transplantation is now commonplace as a result of advances in surgical techniques and postoperative management protocols. Although 1- and 5-year functional and survival data after lung transplantation are well known, sparse information is available regarding functional status of recipients surviving beyond 5 years. METHODS: The medical records and pulmonary function study results of lung transplant recipients who had survived at least 5 years as of September 1995 were retrospectively reviewed. RESULTS: Of the 76 transplantations performed between November 1983 and September 1990, 30 (39.5%) were double lung transplantations, and 46 (60.5%) were single lung transplantations. Thirty-one recipients were alive 5 years after transplantation (12 double lung transplantations, 19 single lung transplantations). The 5-, 6-, and 7-year survival rates were 44%, 34%, and 29%, respectively. There was no association or difference in cytomegalovirus status, sex, and blood group between those who died within 5 years and those who survived beyond 5 years. The median percent predicted FEVs for single and double lung transplant recipients were as follows: 5 yrs-75%, 75%; 6 years-73%, 75%; 7 years-68%, 73%. The proportion of recipients with bronchiolitis obliterans syndrome according to published criteria was as follows: stage 0, 32%; stage I, 19%; stage II, 16%; and stage III, 19%. The functional status (i.e., active, working, disabled) 5 years after transplantation was as follows: active/working, 74%; active but not working, 13%; some limitation/independent, 10%; and disabled, 3%. CONCLUSION: Bronchiolitis obliterans syndrome is a frequent occurrence in long-term survivors. Nevertheless, in spite of this condition, most recipients have acceptable lung function, are active, and are generally working.