Occurrence of Ornithodoros brasiliensis Aragão (Acari: Argasidae) in São Francisco de Paula, RS, Southern Brazil.

There have been no reports of the endemic Ornithodoros brasiliensis (Aragão) in Rio Grande do Sul, southern Brazil, since the 1950s. In January 2007, 21 O. brasiliensis ticks were collected in a rural area named "Cruzinha" in the municipality of São Francisco de Paula, RS, and another population was sampled later that year (October) in Vargem do Cedro, another rural area of São Francisco de Paula, following reports of human parasitism by ticks. The reappearance of this tick is a reason for concern in terms of public health.

Insulin resistance in pulmonary arterial hypertension.

Although obesity, dyslipidemia and insulin resistance (IR) are well known risk factors for systemic cardiovascular disease, their impact on pulmonary arterial hypertension (PAH) is unknown. The present authors' previous studies indicate that IR may be a risk factor for PAH. The current study has investigated the prevalence of IR in PAH and explored its relationship with disease severity. Clinical data and fasting blood samples were evaluated in 81 nondiabetic PAH females. In total, 967 National Health and Nutrition Examination Surveys (NHANES) females served as controls. The fasting triglyceride to high-density lipoprotein cholesterol ratio was used as a surrogate of insulin sensitivity. While body mass index was similar in NHANES versus PAH females (28.6 versus 28.7 kg.m(-2)), PAH females were more likely to have IR (45.7 versus 21.5%) and less likely to be insulin sensitive (IS; 43.2 versus 57.8%). PAH females mostly (82.7%) had New York Heart Association (NYHA) class II and III symptoms. Aetiology, NYHA class, 6-min walk-distance and haemodynamics did not differ between IR and IS PAH groups. However, the presence of IR and a higher NYHA class was associated with poorer 6-months event-free survival (58 versus 79%). Insulin resistance appears to be more common in pulmonary arterial hypertension females than in the general population, and may be a novel risk factor or disease modifier that might impact on survival.

A case of successful treatment of cutaneous Acanthamoeba infection in a lung transplant recipient.

Acanthamoeba species are known to cause 2 well-described entities: (1) granulomatous amoebic encephalitis (GAE), which usually affects immunocompromised hosts, and (2) keratitis, which typically follows trauma associated with contamination of water or contact lenses. Less common manifestations include pneumonitis and a subacute granulomatous dermatitis. We describe a case of granulomatous dermatitis secondary to Acanthamoeba infection in a lung transplant recipient and a successful outcome following treatment with lipid formulation of amphotericin B and voriconazole. We believe this is the second case report describing disseminated Acanthamoeba infection in a lung transplant recipient. We also describe successful outcome with a combination of lipid formulation of amphotericin B and voriconazole, drugs that have not been previously reported to treat Acanthamoeba.

Diagnostic yield of screening colonoscopies in lung transplant candidates.

BACKGROUND: Colonoscopy has been used to screen lung transplant candidates for colorectal diseases that would preclude transplantation. The diagnostic yield of this procedure is unknown. METHODS: This is a retrospective cohort study of patients 50 years of age and over who underwent lung transplant evaluations from 1996 to 1999. We assessed the prevalence and location of colonoscopic abnormalities, the predictive value of risk factors for colonic neoplasms, and the impact of colonoscopic findings on management. RESULTS: Thirty-one patients were evaluated. Twenty-four patients had at least one abnormal endoscopic finding. Six patients (19%) had adenomatous polyps; no carcinomas were detected. The 13 patients with risk factors were more likely to have adenomas (relative risk=2.8, P=0.2). The negative predictive value of risk factors for adenomas was 89%. One patient's management was altered and none were denied transplant listing because of the colonoscopic findings. CONCLUSIONS: Screening colonoscopy did not substantively alter the management of lung transplant candidates. More selective screening strategies may be warranted.

RAD in stable lung and heart/lung transplant recipients: safety, tolerability, pharmacokinetics, and impact of cystic fibrosis.

BACKGROUND: RAD is a novel macrolide with potent immunosuppressive and antiproliferative activities. This study characterizes the safety, tolerability, and pharmacokinetics of two different single oral doses of RAD in stable lung and heart/lung transplant recipients with and without cystic fibrosis (CF). METHODS: This was a Phase I, multicenter, randomized, double-blind, two-period, two-sequence, crossover study. Single doses of RAD capsules at doses of 0.035 mg/kg (2.5 mg maximum) or 0.10 mg/kg (7.5 mg maximum) were administered with cyclosporine (Neoral [cyclosporine, USP] modified), steroids, and azathioprine on Day 1. The alternate dose was administered on Day 16. Laboratory assessments, vital signs, and adverse events were recorded throughout the study. RAD pharmacokinetic profiles were assessed over a 7-day period following each dose. Steady-state cyclosporine (CsA) profiles were assessed at baseline and with each RAD dose; RAD and CsA trough concentrations were obtained throughout the study period. RESULTS: Of the 20 patients randomized, 8 had CF and 12 did not. Single doses of RAD were safe and well tolerated. Headache was the most common side effect. RAD produced a mild, dose-dependent, reversible decrease in platelet and leukocyte counts. Cholesterol and triglycerides were minimally affected. At both doses, CF patients had significantly lower peak concentrations of RAD than did non-CF patients (p = 0.03); however, overall exposure (area under the curve/dose) was not different between the groups (p = 0.63). At the higher dose, there was a clinically minor under-proportionality in AUC, averaging -11%. Steady-state pharmacokinetics of CsA were not affected by RAD co-administration.RAD was safe and well tolerated by stable lung and heart/lung transplant recipients with and without CF. The presence of CF did not influence the extent of RAD exposure. Single doses of RAD did not affect the pharmacokinetics of CsA. Ongoing studies are assessing the long-term safety and efficacy of RAD in lung and heart/lung transplantation.

Inducible nitric oxide synthase transcription in human lung transplantation.

BACKGROUND: Recent animal data suggest that inducible nitric oxide synthase (iNOS) mRNA expression in the bronchoalveolar lavage (BAL) may be useful for the diagnosis of lung rejection. The aim of this study was to evaluate iNOS mRNA transcription in the BAL fluid of human lung allografts. METHODS: iNOS mRNA transcription was quantified by competitive reverse transcription-polymerase chain reaction in 51 BAL cell pellets of lung transplant patients. According to bacteriological and histological results, BAL samples were divided into three groups: normal (n=21), acute rejection (AR, n=15), and infection (INF, n=15). RESULTS: Compared with the control group, iNOS transcription increased significantly with INF (P=0.0005) but only slightly with AR (P>0.05). INF values were significantly higher than AR values (P=0.0029). CONCLUSION: BAL iNOS mRNA transcript determination by competitive reverse transcription-polymerase chain reaction may be useful in differentiating infected from normal and/or acutely rejecting allografts.

Quantification of cytotoxic T-cell gene transcripts in human lung transplantation.

BACKGROUND: Differentiating between acute rejection and cytomegalovirus (CMV) infection is one of the major challenges of lung transplantation. The aims of this study were to: (1) quantify the transcription of the cytotoxic T lymphocyte (CTL) effector molecules in the bronchoalveolar lavage (BAL) of lung transplant recipients and (2) evaluate the clinical usefulness of this technique. METHODS: Sixty-six single-lung, double-lung, or heart-lung transplant patients were prospectively enrolled in the study. BAL was performed either for routine surveillance or for acute graft dysfunction. RNA was extracted from BAL cell pellets and underwent competitive reverse transcription-assisted polymerase chain reaction (RT-PCR) for perforin, granzyme B, granulysin, and Fas ligand. Gene transcript analysis was compared to clinical diagnosis established by conventional methods [BAL microbiological and transbronchial biopsy (TBB) analyses]. RESULTS: After exclusion of several BAL according to the study criteria, 62 BAL were submitted for data analysis. Significantly higher expression of all the analyzed transcripts was found during CMV infection, compared with each of the other defined diagnostic categories, namely nonsignificant pathology, acute rejection, and nonviral pulmonary infection. CONCLUSION: Quantification by competitive RT-PCR of the CTL effector molecule transcripts (perforin, granzyme B, granulysin, and Fas ligand) could represent a valuable tool for the differential diagnosis of graft dysfunction in lung transplantation.

Dendritic cells and macrophages in lung allografts: A role in chronic rejection?

Antigen presentation by lung macrophages/dendritic cells (DC) is thought to be important in obliterative bronchiolitis/bronchiolitis obliterans syndrome (OB/BOS), which severely limits survival post-lung transplantation. However, a recent study found minimal numbers of DC in lung allografts. We looked at numbers and phenotype of macrophages/DC in lung allografts using endobronchial biopsy (EBB) and transbronchial biopsy (TBB) from 22 lung transplant patients. Biopsies were stained with monoclonal markers of DC (CD1a, RFD1, and major histocompatibility complex [MHC] Class II), and "suppressor macrophages" (RFD1 and RFD7). Dendritic cells were also stained for the costimulatory molecules CD80 and CD86. Significantly greater numbers of DC/high-power field (HPF) were seen in biopsies when we defined DC using dendritic morphology and Class II MHC expression instead of CD1a expression. Dendritic cell numbers were significantly higher in eight patients with OB/BOS compared with 14 stable patients. Fifty percent of DC expressed CD86 and 20% expressed CD80. There was no difference in CD80 or CD86 expression between OB/BOS patients and stable patients. There was no correlation between DC numbers and presence or absence of acute rejection (AR), and/or cytomegalovirus (CMV) pneumonitis on current or prior biopsies. There were significantly more MHC Class II DC in EBB compared with TBB. We found minimal staining for lung macrophages capable of suppressing T-cell inflammation. We conclude that studies of lung allografts may underestimate DC numbers if relying on CD1a as the sole marker of DC. DC are increased in patients with OB/BOS compared with stable patients. EBB may be more important than TBB in looking for inflammatory changes of OB. DC expressing costimulatory molecules are present in lung allografts, and costimulatory pathway blockade may be useful in human lung allografts. Also, the absence of "suppressor" macrophages may increase susceptibility of human lung allografts to the rejection process.

Tick-borne pulmonary disease: update on diagnosis and management.

Ticks are capable of transmitting viruses, bacteria, protozoa, and rickettsiae to man. Several of these tick-borne pathogens can lead to pulmonary disease. Characteristic clinical features, such as erythema migrans in Lyme disease, or spotted rash in a spotted fever group disease, may serve as important diagnostic clues. Successful management of tick-borne diseases depends on a high index of suspicion and recognition of their clinical features. Patients at risk for tick bites may be coinfected with two or more tick-borne pathogens. A Lyme vaccine has recently become available for use in the United States. Disease prevention depends on the avoidance of tick bites. When patients present with respiratory symptoms and a history of a recent tick bite or a characteristic skin rash, a differential diagnosis of a tick-borne pulmonary disease should be considered. Early diagnosis and appropriate antibiotic therapy for these disorders lead to greatly improved outcomes.

Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials.

BACKGROUND: Low-molecular-weight heparins may simplify the management of deep venous thrombosis. A critical clinical issue is whether this more convenient therapy is as safe and effective as treatment with unfractionated heparin. PURPOSE: To compare the safety and efficacy of low-molecular-weight heparins with those of unfractionated heparin for treatment of acute deep venous thrombosis. DATA SOURCES: Reviewers identified studies by searching MEDLINE, reviewing references from retrieved articles, scanning abstracts from conference proceedings, and contacting investigators and pharmaceutical companies. STUDY SELECTION: Randomized, controlled trials that compared a low-molecular-weight heparin preparation with unfractionated heparin for treatment of acute deep venous thrombosis. DATA EXTRACTION: Two reviewers extracted data independently. Reviewers evaluated study quality using a validated four-item instrument. DATA SYNTHESIS: Eleven of 37 studies met inclusion criteria for three major outcomes. Most studies used proper randomization procedures, but only one was double-blinded. Compared with unfractionated heparin, low-molecular-weight heparins reduced mortality rates over 3 to 6 months of patient follow-up (odds ratio, 0.71 [95% CI, 0.53 to 0.94]; P = 0.02). For major bleeding complications, the odds ratio favored low-molecular-weight heparins (0.57 [CI, 0.33 to 0.99]; P = 0.047), but the absolute risk reduction was small and not statistically significant (0.61% [CI, -0.04% to 1.26%]; P = 0.07). For preventing thromboembolic recurrences, low-molecular-weight heparins seemed as effective as unfractionated heparin (odds ratio, 0.85 [CI, 0.63 to 1.14]; P > 0.2). CONCLUSIONS: Low-molecular-weight heparin treatment reduces mortality rates after acute deep venous thrombosis. These drugs seem to be as safe as unfractionated heparin with respect to major bleeding complications and appear to be as effective in preventing thromboembolic recurrences.

Recurrent Pneumocystis carinii colonization in a heart-lung transplant recipient on long-term trimethoprim-sulfamethoxazole prophylaxis.

INTRODUCTION: In the setting of organ transplantation, prior to prophylaxis, Pneumocystis carinii pneumonia (PCP) had been a common clinical problem, particularly in heart-lung and lung recipients who receive long-term immunosuppressive therapy to prevent allograft rejection. Continuous oral trimethoprim-sulfamethoxazole (TMP-SMX) has been highly effective in preventing PCP in these patients. REPORT: In this paper we report a case of recurrent Pneumocystis carinii infection in a chronic (> 15 years) heart-lung allograft recipient on long-term TMP-SMX prophylaxis. Twice, in 1995 and again in 1998, Pneumocystis carinii infection was diagnosed by bronchoalveolar lavage (BAL), in the same patient, despite continued oral TMP-SMX (960 mg TMP/4800 mg SMX per week) prophylaxis. The subject was not lymphopenic (his CD4 count was 569/mm3) and there was no associated deterioration in pulmonary function, nor evidence of hypoxemia. CONCLUSION: This case demonstrates that asymptomatic Pneumocystis carinii lung infections may recur in chronic heart-lung transplant recipients who take standard oral PCP prophylaxis.

Assessing and modifying the risk of postoperative pulmonary complications.

Preoperative pulmonary evaluation and preparation involve first identifying patients at risk for complications and then attempting to modify that risk. For most patients without underlying lung disease, a thorough history and physical examination and preoperative instruction in the use of incentive spirometry is sufficient. In patients with known or suspected lung disease, preoperative pulmonary function tests, while unproven as prognostic tools, may reduce risk by aiding in medical management, and in the case of the lung resection candidate, by helping determine very directly his or her viability for the procedure.

Diaphragmatic paralysis due to Lyme disease.

Lyme disease is a tick-borne spirochaete infection which, in a proportion of patients, can lead to neuropathy. This article describes a case of diaphragmatic paralysis due to Lyme disease. A 39-yr-old male presented to the hospital because of an acute left facial palsy. Six weeks prior to admission he had developed a circular rash on his left flank during a camping holiday. He also complained of shortness of breath and arthralgia for 1 week. His chest radiograph demonstrated a raised right hemi-diaphragm. Diaphragmatic paralysis was confirmed by fluoroscopy (a positive sniff test). Serology revealed evidence of recent infection by Borrelia burgdorferi. On the basis of the patient's clinical presentation, a recent history of erythema migrans, and positive Lyme serology, a diagnosis of neuroborreliosis was made. He received oral doxycycline therapy (200 mg x day(-1)) for three weeks. Facial and diaphragmatic palsies resolved within eight weeks. On the basis of this case, a diagnosis of Lyme disease should be considered in patients from endemic regions with otherwise unexplained phrenic nerve palsy.

Tropical pulmonary eosinophilia.

Tropical pulmonary eosinophilia (TPE) usually affects people living in the tropics, especially those in Southeast Asia, India, and certain parts of China and Africa. However, owing to the rising frequency of world-wide travel and the migration between continents, this disease is increasingly seen in the West, where the diagnosis can be easily missed since it is rarely encountered and can mimic many other conditions. Cases of TPE have typically been reported to masquerade as acute or refractory bronchial asthma. TPE results from a hypersensitivity reaction to lymphatic filarial parasites found in endemic regions. There is evidence that it is more likely to occur in nonimmune individuals, ie, visitors to endemic regions, than in individuals of endemic populations who have developed immunity to filarial infections. Clinical features include paroxysmal cough, wheezing and dyspnea, and systemic manifestations such as fever and weight loss. A history of residence in a filarial endemic region and a finding of peripheral eosinophilia >3,000/mm3 should initiate a consideration of this disease. Other criteria for the diagnosis of TPE include absence of microfilariae in the blood, high titers of antifilarial antibodies, raised serum total IgE >1,000 U/mL, and a favorable response to the antifilarial, diethylcarbamazine, which is the recommended treatment. This disease, if left untreated or treated late, may lead to long-term sequelae of pulmonary fibrosis or chronic bronchitis with chronic respiratory failure. Herein lies the importance of early diagnosis and treatment of TPE.