Clinical spectrum of gram-positive infections in lung transplantation.

PURPOSE: Gram-positive (GP) organisms are among the most common cause of infections in early postsurgical and immunocompromised populations. Patients recovering from lung transplantation (LT) are particularly susceptible owing to the physiologic stress imposed by surgery and induction with intense immunosuppression. Sites, types, and timing of GP infections following LT are not well documented. This report describes the clinical spectrum of GP infections and their effects on surgical airway complications (SAC) and bronchiolitis obliterans syndrome (BOS) following LT. METHODS AND MATERIALS: Data were collected from 202 patients undergoing 208 LT procedures at a single institution between November 1990 and November 2005. Data were retrospectively analyzed according to timing, location, and causative pathogen. RESULTS: In the median follow-up period of 2.7 years (range, 0-13.6 years), 137 GP infections were confirmed in 72 patients. Sites of infection included respiratory tract (42%), blood (27%), skin, wound and catheter (21%), and other (10%). GP pathogens identified were Staphylococcus species (77%), Enterococcus species (12%), Streptococcus species (6%), Pneumococcus (4%), and Eubacterium lentum (1%). The likelihood of SAC and BOS was increased in lung allograft recipients with GP pneumonia as compared with those without (hazard ratio 2.1; 95% confidence interval=1.5-3.1). CONCLUSIONS: GP organisms were responsible for infections in 40% of lung allograft recipients and most commonly isolated from the respiratory tract and blood stream. Staphylococcal species were most frequently identified, 42% of which were methicillin-resistant Staphylococcus aureus (MRSA). Given the strong association of respiratory tract infections with the development of SAC and BOS, empiric antimicrobial strategies after LT should include agents directed against GP organisms, especially MRSA.

Clostridium difficile colitis in lung transplantation.

PURPOSE: Clostridium difficile colitis (CDC) is the most common nosocomial infection of the gastrointestinal tract in patients with recent antibiotic use or hospitalization. Lung transplant recipients receive aggressive antimicrobial therapy postoperatively for treatment and prophylaxis of respiratory infections. This report describes the epidemiology of CDC in lung recipients from a single center and explores possible associations with bronchiolitis obliterans syndrome (BOS), a surrogate marker of chronic rejection. METHODS: Patients were divided into those with confirmed disease (CDC+) and those without disease (CDC-) based on positive C. difficile toxin assay. Because of a bimodal distribution in the time to develop CDC, the early postoperative CDC+ group was analyzed separately from the late postoperative CDC+ cohort with respect to BOS development. RESULTS: Between 1990 and 2005, 202 consecutive patients underwent 208 lung transplantation procedures. Of these, 15 lung recipients developed 23 episodes of CDC with a median follow-up period of 2.7 years (range, 0-13.6). All patients with confirmed disease had at least 1 of the following 3 risk factors: recent antibiotic use, recent hospitalization, or augmentation of steroid dosage. Of the early CDC+ patients, 100% developed BOS, but only 52% of the late CDC+ patients developed BOS, either preceding or following infection. CONCLUSION: CDC developed in 7.4% of lung transplant patients with identified risk factors, yielding a cumulative incidence of 14.7%. The statistical association of BOS development in early CDC+ patients suggests a relationship between early infections and future chronic lung rejection.

Histoplasma capsulatum polysaccharide antigen detection in diagnosis and management of disseminated histoplasmosis in patients with acquired immunodeficiency syndrome.

PURPOSE: Disseminated histoplasmosis is a serious and often rapidly progressive, opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), supporting the importance of rapid diagnostic tests. We investigated Histoplasma capsulatum polysaccharide antigen (HPA) detection, a promising new method for rapid diagnosis of histoplasmosis. PATIENTS AND METHODS: Sixty-one cases of disseminated histoplasmosis in patients with AIDS form the basis of this report. Control cases were patients with AIDS who had other opportunistic infections and whose cultures were negative for H. capsulatum. A slightly modified radioimmunoassay procedure was used to measure the levels of HPA in urine and blood specimens. RESULTS: High levels of HPA were detected in the urine of 59 of 61 (96.7%) and the blood of 37 of 47 (78.7%) patients with AIDS complicated by disseminated histoplasmosis. Treatment with amphotericin B reduced levels of HPA in the urine in 19 of 21 (90.5%) and the serum of all 10 patients tested. HPA levels increased in the urine in all eight and in the serum in all five patients with culture-proven relapse. CONCLUSION: In conclusion, HPA detection offers a rapid method for diagnosing disseminated histoplasmosis. Additional experience is required to establish the role of this test in monitoring the effects of treatment and in identifying relapse in patients with AIDS.

Histoplasmosis in patients with acquired immunodeficiency syndrome. Hematologic and bone marrow manifestations.

In areas where Histoplasma capsulatum infections are endemic in the United States, there is an increasing frequency of progressive disseminated histoplasmosis (PDH) as an opportunistic infection in patients with acquired immune deficiency syndrome (AIDS). The bone marrow and peripheral blood (PB) specimens in 13 patients with AIDS and PDH were reviewed. Anemia, leukopenia, and thrombocytopenia were found in 12, 10, and 7 patients, respectively. Circulating organisms were detected in the blood smears or buffy coat preparations from five patients and were associated with PB nRBCs and severe absolute monocytopenia. Morphologically, the marrow specimens showed one of four patterns: (1) no morphologic evidence of infection (two patients, one with a positive marrow culture); (2) discrete granulomas (two patients, both with positive marrow cultures); (3) lymphohistiocytic aggregates (six patients, four with positive marrow cultures); and (4) diffuse macrophage infiltrates (three patients, all with positive marrow cultures). Morphologic examination of the bone marrow combined with cultures is useful in diagnosing disseminated histoplasmosis in patients with AIDS. However, the morphologic findings in the bone marrow may be different in patients with AIDS compared with non-AIDS patients, and seemingly nondiagnostic morphologic features must be approached with a high degree of suspicion in diagnosing infections with H. capsulatum in this population.

Effect of nonadiabaticity of dust charge variation on dust acoustic waves: generation of dust acoustic shock waves.

The effect of nonadiabaticity of dust charge variation arising due to small nonzero values of tau(ch)/tau(d) has been studied where tau(ch) and tau(d) are the dust charging and dust hydrodynamical time scales on the nonlinear propagation of dust acoustic waves. Analytical investigation shows that the propagation of a small amplitude wave is governed by a Korteweg-de Vries (KdV) Burger equation. Notwithstanding the soliton decay, the "soliton mass" is conserved, but the dissipative term leads to the development of a noise tail. Nonadiabaticity generated dissipative effect causes the generation of a dust acoustic shock wave having oscillatory behavior on the downstream side. Numerical investigations reveal that the propagation of a large amplitude dust acoustic shock wave with dust density enhancement may occur only for Mach numbers lying between a minimum and a maximum value whose dependence on the dusty plasma parameters is presented.

Collisionless damping of nonlinear dust ion acoustic wave due to dust charge fluctuation.

A dissipation mechanism for the damping of the nonlinear dust ion acoustic wave in a collisionless dusty plasma consisting of nonthermal electrons, ions, and variable charge dust grains has been investigated. It is shown that the collisionless damping due to dust charge fluctuation causes the nonlinear dust ion acoustic wave propagation to be described by the damped Korteweg-de Vries equation. Due to the presence of nonthermal electrons, the dust ion acoustic wave admits both positive and negative potential and it suffers less damping than the dust acoustic wave, which admits only negative potential.

Rural-urban migration, informal sector and development policies: a theoretical analysis.

"A theoretical model of rural-urban migration has been developed with special reference to the informal sector. The wage rate and employment in the informal sector are determined endogenously. The paper shows the simultaneous existence of open unemployment and informal sector in the urban area in migration equilibrium. The effects of alternative subsidy policies on unemployment and welfare of the workers are studied." The model is intended primarily for use in analyzing trends and policies in developing countries.

PIP: A Harris-Todaro type of dual economy model, with the urban sector consisting of a formal and an informal subsector, has been refined to include open urban unemployment, even in migration equilibrium, despite the existence of the informal sector, in order to study the effects of alternative development policies of the informal sector on the open unemployment in the urban sector. In addition, the effects of different policies on the welfare of Indian society are examined using the welfare measure suggested by Sen. The model uses four income groups. The production function of the urban formal sector is set equal to the level of employment, the amount of intermediate input, and the capital stock. Further specifications are made for cost, equilibrium conditions, and input demand functions. Wages are considered a policy variable. Informal sector demand function of the product is set equal to two positive constants and price subsidies. The formula is further specified by the wage rate and the total labor cost, capital borrowed at a rate of interest, and additional loans at a higher interest rate. The rural sector uses labor for production, and an assumption is made about the marginal productivity pricing of labor. The marketable surplus is determined, with the selling price of food as the policy variable. Price subsidy policy for the informal sector reduces unemployment as product prices rise and wages decline. Capital subsidy to the informal sector exacerbates unemployment as product prices decline and wages rise. Wage subsidy policy relating to the urban formal sector reduces the level of open unemployment as informal wages decline; but price or wage subsidy policy related to the rural sector aggravates open unemployment as product prices and wages rise. Additional wage subsidies to the rural sector create an equilibrium which includes higher informal sector prices, wages, and unemployment. The impact on the welfare of workers shows that price subsidies to the informal sector improves the welfare of society. The model is suitable for a closed economy such as India's where food imports are minimal.

Migration, unemployment and development: a dynamic two-sector analysis.

"A time-minimizing problem of attaining a full employment state is solved in a dual-economy model with [the] Harris-Todaro migration mechanism and with a positive level of urban unemployment in the starting period. It appears that the optimum solution lies in the specialization of investment in the urban sector at least in the initial stage of development if the per-capita stock in the urban sector is very small in the starting period."

Equilibrium urban unemployment in developing countries: is migration the culprit?

"This paper challenges the prediction of Todaro's model of rural-to-urban migration that an 'increase in urban employment increases urban unemployed.' It is shown that if the urban demand for labor is isoelastic or inelastic, creation of urban jobs causes urban unemployment to decline and urban-to-rural migration to take place. Moveover, urban job creation always reduces the rate of urban unemployment. The paper then remodels the urban job search process and derives the result that equilibrium urban unemployment would not vanish even if the urban-rural wage gap were eliminated." The geographical focus is on developing countries.

Low-frequency wave modulations in an electronegative dusty plasma in the presence of charge variations.

The effects of dust charge variations on low-frequency wave modulations in an electronegative dusty plasma are investigated. The dynamics of the modulated wave is governed by a nonlinear Schrödinger equation with a dissipative term. The dissipation arises due to the nonsteady (nonadiabatic) dust charge variations. Theoretical and numerical investigations predict the formation of dissipative bright (envelope) and dark solitons. The nonsteady charge-variation-induced dissipation reduces the modulational instability growth rate and introduces a characteristic time scale to observe bright solitons. Results are discussed in the context of electronegative dusty plasma experiments.

Harris-Todaro migration-mechanism and the optimum development of the urban sector.

"A time-minimization problem of attaining a full-employment state is solved in a dual economy model where the rural-urban migration mechanism is of [the] Harris-Todaro type. The optimum solution may appear as a policy of urban development at the most rapid rate."

Long-term amphotericin B therapy for disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome (AIDS).

STUDY OBJECTIVE: To assess the efficacy and toxicity of long-term maintenance amphotericin B therapy in preventing relapses after treatment in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. DESIGN: Open, nonrandomized pilot study. SETTING: Three private, university-affiliated community hospitals. PATIENTS: We studied 22 consecutive patients with disseminated histoplasmosis and human immunodeficiency virus (HIV) infection. Sixteen patients completed the study, 5 patients died before completing the initial intensive phase of treatment, and 1 patient received a different treatment regimen. INTERVENTIONS: Seven patients were treated with an initial intensive course of 1000 mg of amphotericin B, followed by weekly infusions of 50 to 80 mg until a cumulative dose of 2000 mg was attained; biweekly infusions of 50 to 80 mg were then continued indefinitely. Nine patients received an initial amphotericin B course of 2000 mg followed by weekly infusions of 80 mg. MEASUREMENTS AND MAIN RESULTS: Of the 7 patients in the 1000-mg intensive regimen group, 6 patients have survived without clinical or laboratory evidence of a histoplasmosis relapse, and 1 died of unrelated causes. Of the 9 patients in the 2000-mg intensive regimen group, 7 patients have survived, 1 patient died of a histoplasmosis relapse, and 1 patient died of other causes. Thus, 13 of 14 patients (93%) who did not die of other causes remained relapse-free. The median follow-up period was 14 months (range, 2 to 23 months). No apparent differences in outcome were observed between patients treated with weekly maintenance regimens and those treated with biweekly maintenance regimens. Sixty-three percent of patients developed intravascular device-related complications. CONCLUSIONS: Long-term, intermittent maintenance amphotericin B therapy in HIV-infected patients with disseminated histoplasmosis is well tolerated and is highly effective in suppressing relapses after treatment.

Antigenic diversity of lipooligosaccharides of nontypable Haemophilus influenzae.

The lipooligosaccharides (LOS) of nontypable Haemophilus influenzae are an antigenically heterogeneous group of macromolecules. Immunodiffusion and enzyme-linked immunosorbent assay inhibition studies with phenol-water-extracted LOS and absorbed antisera specific for the oligosaccharide portion of the LOS identified six LOS strain-specific antigens. To facilitate screening large numbers of strains to search for LOS antigenic heterogeneity, a system utilizing proteinase K whole cell digests in Western blots was developed. Seventy-two nontypable H. influenzae LOS extracts were analyzed in this Western blot assay. Thirty-seven of these extracts could be segregated into 10 antigenically distinct LOS groups based on immunologic recognition by one or more of the rabbit antisera. Thirty-five of the strains did not contain these LOS antigens. These results demonstrate that antigenic differences exist among the LOS of nontypable H. influenzae strains, and this heterogeneity has the potential to be used to establish an LOS-based serogrouping system.

Mycobacterium kansasii among patients infected with human immunodeficiency virus in Kansas City. Kansas City AIDS Research Consortium.

Previous reports of infection due to Mycobacterium kansasii among patients infected with human immunodeficiency virus (HIV) have conflicted with regard to the significance of the isolate; the clinical, radiographic, and laboratory features of the disease; and the response to therapy. To clarify the spectrum of M. kansasii infection in this population, we conducted a retrospective study of 35 patients. Twenty-eight of these patients were believed to have disease due to M. kansasii, while the remaining seven patients were probably colonized with the organism. All but two patients presented with advanced HIV infection; the median CD4 cell count was 12/microL. Most patients with pulmonary disease presented with fever, cough, and dyspnea, but only eight of these 22 patients had radiographic findings of either pulmonary cavitation or predominantly upper-lobe disease. Ten patients had M. kansasii isolated from blood or bone marrow. The majority of patients with pulmonary or disseminated disease responded to therapy. However, 11 patients died either before mycobacterial infection was diagnosed or early in the course of treatment, and two had a relapse of infection during therapy.

Prospective study of histoplasmosis in patients infected with human immunodeficiency virus: incidence, risk factors, and pathophysiology.

Histoplasmosis is a common opportunistic infection in patients with human immunodeficiency virus (HIV) infection who reside in areas where Histoplasma capsulatum is endemic. We undertook a prospective study of a cohort of 304 HIV-Infected patients in Kansas City from October 1990 through March 1993 to define the incidence-specific risk factors, and pathophysiology of histoplasmosis. The annual incidence of histoplasmosis was 4.7%; 74% of the patients with histoplasmosis were symptomatic (all of whom had disseminated disease). A history of exposure to chicken coops, a positive baseline serology for complement-fixing antibodies to Histoplasma mycelium antigen, and a baseline CD4+ lymphocyte count of < 150/microL were associated with an increased risk for histoplasmosis. Histoplasmin reactivity and the presence of pulmonary calcifications were not useful markers for patients at high risk. Symptomatic infection occurred in 9.9% of patients with evidence of prior exposure to H. capsulatum, in 4.0% of patients without documented prior exposure, and in 3.0% of patients who were anergic; these findings suggest that the pathophysiology of histoplasmosis in patients with AIDS involves reactivation of latent infection in some cases and dissemination of exogenously acquired infection in other cases.