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Objectives: This exploratory study examined the facilitators of and barriers to acceptance of pre‐exposure prophylaxis (PrEP) and potential risk compensation behaviour emerging from its use among men who have sex with men (MSM) and transgender individuals (TGs) in India. Methods: A questionnaire was administered to 400 individuals registered with a targeted intervention programme. Logistic regression models were used to identify facilitators of and barriers to PrEP acceptance. Results: The respondents consisted of 68% MSM and 32% TGs. Risk behaviour categorization identified 40% as low risk, 41% as medium risk and, 19% as high risk for HIV infection. About 93% of the respondents were unaware of PrEP, but once informed about it, 99% were willing to use PrEP. The facilitators of PrEP acceptance were some schooling [odds ratio (OR) 2.16; P = 0.51], being married or in a live‐in relationship (OR 2.08; P = 0.46), having a high calculated risk (OR 3.12; P = 0.33), and having a high self‐perceived risk (OR 1.8; P = 0.35). Increasing age (OR 2.12; P = 0.04) was a significant barrier. TGs had higher odds of acceptance of PrEP under conditions of additional cost (OR 2.12; P = 0.02) and once‐daily pill (OR 2.85; P = 0.04). Individuals identified as low risk for HIV infection showed lower odds of potential risk compensation, defined as more sexual partners (OR 0.8; P = 0.35), unsafe sex with new partners (OR 0.71; P = 0.16), and decreased condom use with regular partners (OR 0.95; P = 0.84), as compared with medium‐risk individuals. The associations, although not statistically significant, are nevertheless important for public health action given the limited scientific evidence on PrEP use among MSM and TGs in India. Conclusions: With high acceptability and a low likelihood of risk compensation behaviour, PrEP can be considered as an effective prevention strategy for HIV infection among MSM and TGs in India. [ABSTRACT FROM AUTHOR]

Methicillin and gentamicin resistant strains of Staphylococcus aureus (MRSA) remains a cause of significant morbidity and mortality. Vancomycin is usually effective against these strains, but toxicity and expense are significant drawbacks. Resistance to the new quinolones has been demonstrated in vitro and during clinical therapeutic trials. Trimethoprim-sulphamethoxazole has proved to be effective in vitro against staphylococcal strains that are resistant to gentamicin, methicillin, and quinolones. As determined by time-kill kinetic studies, trimethoprim-sulphamethoxazole was rapidly bactericidal. Clinical evaluation of trimethoprim-sulphamethoxazole against MRSA in patients with osteomyelitis is under study. We believe that our data support the use of trimethoprim-sulphamethoxazole as a potentially economical and effective alternative for the treatment of infections caused by MRSA. [ABSTRACT FROM AUTHOR]

This study sought to describe the development of HIV counselling and testing services in a rural private hospital and to explore the factors associated with reasons for seeking HIV testing and sexual behaviours among adults seeking testing in the rural hospital. Data for this study were drawn from a voluntary counselling and testing clinic in a private hospital in rural Andhra Pradesh state in southern India. In total, 5,601 rural residents sought HIV counselling and testing and took part in a behavioural risk-assessment survey during October 2003-June 2005. The prevalence of HIV was 1.1%. Among the two reported reasons for test-seeking--based on past sexual behaviour and based on being sick at the time of testing--men, individuals reporting risk behaviours, such as those having multiple pre- and postmarital sexual partners, individuals whose recent partner was a sex worker, and those who reported using alcohol before sex, were more likely to seek testing based on their past sexual behaviour. Men also were more likely to seek testing because they were sick. The findings from this large sample in rural India suggest that providing HIV-prevention and care services as part of an ongoing system of healthcare-delivery may benefit rural residents who otherwise may not have access to these services. The implications of involving the private sector in HIV-related service-delivery and in conducting research in rural areas are discussed. It is argued that services that are gaining prominence in urban areas, such as addressing male heterosexual behaviours and assessing the role of alcohol-use, are equally relevant areas of intervention in rural India. [ABSTRACT FROM AUTHOR]

Background: Prior research has indicated patient dissatisfaction with the odor, size, and taste of cyclosporine capsules, as well as the halitosis and body odor the capsules can cause.Objectives: The purposes of this investigation were to (1) compare the overall cyclosporine capsule preference (GENGRAF vs NEORAL in stable, solid-organ transplant recipients, (2) assess patient preference based on specific capsule attributes, and (3) determine the reliability of the Cyclosporine Capsule SatiSfaCtion Survey (original to this study).Methods: In this multicenter, randomized, open-label, parallel-group, preference study, patients were recruited from 144 centers in North America with established transplant programs. Solid-organ transplant recipients who had taken stable doses of cyclosporine (Neoral) for >/=2 consecutive months were randomized in a 9:1 ratio to receive another cyclosporine formulation (Gengraf) or to remain on Neoral therapy. Patients completed the Cyclosporine Capsule Satisfaction Survey prior to randomization (baseline survey) and after taking the study drug for 4 weeks (final survey). The survey consisted of multiple attribute items with high face validity in assessing patients' perceptions and preferences with regard to their overall experience, as well as specific attributes of cyclosporine capsules known to affect patient acceptance.Results: The intent-to-treat population included 1906 patients (1211 men, 693 women [sex unknown in 2 patients]; mean [SD] age, 50.2 [12.4] years). A total of 1708 patients were switched to Gengraf; 198 continued on Neoral. Based on their overall experience with both capsule formulations, the majority of patients switched to Gengraf (61.9%) responded that they preferred the Gengraf capsule, compared with 13.7% who preferred the Neoral capsule and 24.4% who indicated no preference (P < 0.001). A similar preference for Gengraf was observed based on capsule odor (66.3%), ease of swallowing (51.5%), taste (57.1%), and impact on breath odor (52.5%) and body odor (48.4%) (P < 0.001 for each test). The results of internal consistency and reproducibility calculations were high for the Cyclosporine Capsule Satisfaction Survey. Internal consistency ranged from ALPHA = 0.84 to 0.95 for the subscales and was ALPHA = 0.95 for the overall score. Ranges for reproducibility in the subscales were r = 0.75 to 0.79, with an overall reproducibility of r = 0.85. Guyatt's responsiveness statistics for the subscale and overall scores were moderately high to very high, indicating that the survey is capable of measuring change in response to treatment.Conclusions: Of the transplant recipients receiving Gengraf in this study, most preferred Gengraf to Neoral based on overall experience, capsule odor, difficulty swallowing, taste, breath odor, and body odor. Among all study patients, fewer patients receiving Gengraf were bothered by capsule odor, difficulty in swallowing, taste, or the impact on breath or body odor compared with patients who continued to receive Neoral. Internal consistency, reproducibility, and responsiveness results show that the Cyclosporine Capsule Satisfaction Survey is a psychometrically valid instrument that is appropriate for use in clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: HIV self-testing (HIVST) has been shown to increase the uptake of HIV testing and help achieve the UNAIDS 95-95-95 targets. This study assessed the acceptability, usability (ease of use and result interpretation) and the willingness to pay for HIVST kits distributed through three distribution models, namely the community-based, PLHIV network-led and private practitioners models, in India., Methods: This cross-sectional study was implemented across 14 states in India between September 2021 and June 2022. All participants could choose between blood-based or oral-fluid-based test kits. Participants were shown a test-kit usage demonstration video, and pre- and post-test counselling was provided for all. Participants were followed-up after testing, and if reported reactive, were further supported for linkage to confirmatory testing and antiretroviral therapy (ART) initiation., Results: Among the 90,605 participants found eligible, 88,080 (97%) accepted an HIVST kit. Among the 87,976 who reported using an HIVST kit, 45,207 (51%) preferred a blood-based kit, and 42,120 (48%) reported testing for the first time. For future testing, 77,064 (88%) reported preferring HIVST over other HIV testing methods. Among those who used the kit, 83,308 (95%) found the kit easy to use, and 83,237 (95%) reported that the test results were easy to interpret. Among those who preferred HIVST for future use, 52,136 (69%) were willing to pay for the kit, with 35,854 (69%) of those willing to pay less than US$ 1.20. Only one instance of social harm was reported, with a participant reporting suicidal tendencies due to discord with their partner. Out of 328 participants (0.4%) who tested reactive with HIVST, 291 (89%) were linked to confirmatory testing; of these, 254 were confirmed HIV positive, and 216 (85%) successfully initiated ART., Conclusions: Overall, we report that nearly all participants were willing to accept HIVST, found the test kits easy to use and interpret, and about two-thirds were willing to pay for HIVST. Given the high levels of acceptance and the ability to reach a large proportion of first-time testers, HIVST in India could contribute to achieving the UNAIDS first 95 and ending the HIV epidemic., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

To explore themes regarding work-related barriers to access to health care, we conducted 32 interviews, 16 with third gender people and 16 with cisgender women, all of whom were all living with HIV in Hyderabad, India. Most respondents were members of Dalit castes and had been living with HIV for several years at the time of the interview. Using thematic content analysis, interviews were coded by two researchers using a social determinants of health conceptual framework. Themes highlighted in this study include the burden of taking time off from work, the loss of pay associated with missing work, and the interruption of gendered care work responsibilities that respondents faced when seeking treatment. Findings from this study support the claim that equitable work policies and practices for marginalized laborers can increase access to medical care for people living with HIV., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Mumbai is one of the most densely populated areas in the world and is a major contributor to the tuberculosis (TB) epidemic in India. A test and treat approach for TB infection (TBI) amongst household contacts (HHC) is part of the national policy for TB preventive treatment (TPT). However, in practice, the use of interferon-gamma release assay (IGRA) tests for infection are limited, and prevalence of TBI in Mumbai is not known., Methods: We conducted a cross-sectional study among HHCs exposed to persons with microbiologically-confirmed, drug-susceptible pulmonary TB that were notified for antituberculosis treatment in Mumbai, India during September-December, 2021. Community-based field workers made home visits and offered IGRA (QuantiFERON-TB ® Gold In-Tube Plus) tests to HHC aged 5 years and older. After ruling out active TB disease, HHC with IGRA-positive test results were referred for TPT. All HHC were monitored for at least 24 months for progression to active TB disease., Results: Among 502 HHCs tested, 273 (54%) had IGRA-positive results. A total of 254 (93%) were classified as TBI and were eligible for TPT, of which 215 (85%) initiated TPT, and 194 (90%) completed TPT successfully. There was substantial variation in rates of TBI per household. In 32% of households, all HHC (100%) were IGRA positive and in 64% of households >50% of HHC were infected. In all, 22 HHCs (4%; 22/558) were diagnosed with TB disease; of these, five HHC were diagnosed during follow up, of which three were IGRA positive and had no evidence of disease at initial screening but chose not to initiate TPT., Conclusion: A test and treat strategy for HHC resulted in the detection of a substantial proportion of TBI and secondary TB cases. Home-based IGRA testing led to high participation rates, clinical evaluations, TPT initiation, and early diagnoses of additional secondary cases. A community-focused, test and treat approach was feasible in this population and could be considered for broader implementation., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. PM declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

The goal of this study was to explore the association between HIV stigma and depression and whether gender moderated this relationship. The theoretical framework for the study combined an adapted version of Goffman's conceptualization of stigma with gender role theory. We surveyed 150 individuals living with HIV in Hyderabad, India (51 cisgender women, 49 cisgender men, and 50 third gender people) on their experiences with HIV stigma. While third gender people had statistically higher scores for HIV stigma over their cisgender counterparts, the association between each of three different forms of stigma (internalized stigma, perceived stigma, and experienced stigma) on depression was negatively moderated by third gender status. This demonstrates that third gender research participants who experienced certain forms of HIV stigma were less likely to be depressed than cisgender participants. These findings indicate resilience amongst third gender people living with HIV and can be used to better tailor social policies and gender-affirming HIV care programs in south India., (© 2022 Wiley Periodicals LLC.)

Mumbai, India's second largest city, has one of the highest prevalences of drug-resistant tuberculosis* (DRTB) in the world. Treatment for DRTB takes longer and is more complicated than treatment for drug-susceptible tuberculosis (TB). Approximately 300 persons receive a new DRTB diagnosis each year in Mumbai's Dharavi slum † ; historically, fewer than one half of these patients complete DRTB treatment. As nationwide restrictions to mitigate the COVID-19 pandemic were implemented, a program to facilitate uninterrupted DRTB care for patients receiving treatment was also implemented. A comprehensive tool and risk assessment provided support to DRTB patients and linked those who relocated outside of Dharavi during the pandemic to DRTB care at their destination. During May 2020-September 2022, a total of 973 persons received DRTB treatment in Dharavi, including 255 (26%) who relocated during treatment. Overall, 25 (3%) DRTB patients were lost to follow-up, a rate substantially lower than the rate before the pandemic (18%). Proactive planning and implementation of simple tools retained patients on treatment during periods of travel restrictions and relocations, improving programmatic outcomes. This approach might aid public health programs serving migrant populations or patients receiving treatment for DRTB during public health emergencies., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: People with Advanced HIV Disease (AHD) are at higher risk of TB coinfection and mortality. However, there are challenges in TB diagnosis with the currently recommended diagnostic tools. WHO recommends lateral flow urine lipoarabinomannan (LF-LAM) assay to assist TB diagnosis among AHD patients. We assessed the utility and acceptability of using urine LF-LAM assay for TB diagnosis among patients at public Antiretroviral Therapy (ART) Centres in Mumbai., Methods: The cross-sectional study was conducted among adult AHD patients accessing care from 17 ART centres during November,2020-June, 2021. Urine LF-LAM was offered as routine care for eligible patients in combination with standard diagnostic tests. We calculated the proportion of positive LF-LAM results by CD4 categories and TB symptoms and performed multivariable logistic regression to determine the factors associated with LF-LAM positivity., Results: Among 2,390 patients, the majority (74.5%) had CD4 between 101-200 cells/mm3. The mean age was 43.7 years (SD:10.6), 68.6% were male, 8.4% had TB symptoms and 88.0% were on ART. The overall proportion of patients with urine LF-LAM positive results was 6.4%. Among PLHIV with CD4≤100 cells/mm3, the positivity was 43.0% and 7.7% in symptomatic and asymptomatic patients, respectively. Among PLHIV with a CD4>100 cells/mm3, the positivity was 26.7% and 2.7% in symptomatic and asymptomatic patients respectively. Urine LF-LAM positivity was higher among inpatients, ART naïve, patients on treatment for <6 months, symptomatic and in WHO clinical stage III/IV of HIV disease as compared to the reference categories. We detected an additional 131 TB cases with urine LF-LAM in combination with the standard diagnostic tests., Conclusion: The study demonstrated the utility of urine LF-LAM for TB diagnosis among AHD patients and the simple, user-friendly test was acceptable as part of routine care. Inclusion of urine LF-LAM test in the current diagnostic algorithm may facilitate early TB diagnosis among AHD patients., Competing Interests: The authors have declared that no competing interests exist.

This mixed-methods study sought to explore gender fluidity among people living with human immunodeficiency virus (HIV) in Hyderabad, India, almost all of whom did not identify as hijra. Sixteen gender-nonconforming people living with HIV completed both surveys and in-depth interviews, exploring their experiences with HIV and gender nonconformity stigma. Interviews were conducted in Hindi and Telugu, digitally audio-recorded, then subsequently translated and analyzed in English, using interpretative phenomenological analysis. Our study highlighted three categories of gender expression: (1) "We have to maintain secrecy about our hijra life": Living secret lives; (2) "What happens if my neighbor sees me here?": Contextual disclosure; (3) "Twenty-four hours a day I will wear a sari": Being fully out. Analysis revealed that many gender-nonconforming people reported identifying with two distinct gender identities: one in the daylight, where they identified as men and fulfilled a role of husband and father with their family, and another at night where they identified otherwise-as women, as third gender, as kothis, hijra, transgender. Themes reinforce a phenomenological interpretation of gender identity and expression in the south Indian context, which is grounded in practices regarding identity's embodiment in clothing, vocal intonation, makeup, and context., (© 2021 Wiley Periodicals LLC.)

Objectives: There is a growing burden of HIV and sex-related diseases in South Asia and India. Sociological research illustrates that key axes of social stratification, such as race and ethnicity, affect social network structure which, in turn, impacts sexual health and wellbeing. Research on networks has increasingly begun to examine the ways in which networks drive or harness sexual behaviors, but has largely neglected the influence of culture and cultural markers in this continuum. Furthermore, much of the existing scholarship has been conducted in the U.S. or in Western contexts. Design: As part of an exploratory effort, we examined how skin color and body mass index (BMI) affected networks among 206 men who have with men (MSM) frequenting sex markets in Hyderabad, India. A novel phone-based network generation method of respondent-driven sampling was used for recruitment. In assessing how skin color and BMI drive these structures, we also compared how these factors contribute to networks relative to two more commonly referenced markers of social difference among Indians, caste and religion. Results: Our findings suggest that skin color and BMI contribute significantly more to network structure than do caste and religion. Conclusions: These findings tentatively illuminate the importance of individual-level heterogeneity in bodily attributes, factors which are seldom considered in conventional approaches to researching how social stratification and health inequalities are animated during the formation of networks.

Contact tracing for venereal disease control has been widespread since 1936 and relies on reported information about contacts' attributes to determine whether two contacts may represent the same individual. We developed and implemented a gold-standard for determining overlap between contacts reported by different individuals using cell phone numbers as unique identifiers. This method was then used to evaluate the performance of using reported names and demographic characteristics to infer overlap. Cell-phone numbers, names and demographic data for a sample of high-risk men in India and their contacts were collected using a novel, hybrid instrument involving both cell-phone data extraction and Computer-Assisted Personal Interviewing (CAPI). Logistic regression was used to model the probability that a pair of contacts reported by different respondents were identical, based on the correspondence between their reported names and attributes. A discrete mixture model is proposed which provides predictions nearly as good as the logistic model but may be used in a new population without re-calibration. Despite achieving AUCs of 0.83-0.86, the low rate of true overlap among a very large number of contact pairs still results in a high rate of false positives. Next generation contact tracing calls for more archived or digital matching processes.

Parvovirus B19 infection is undiagnosed in recipients undergoing solid organ transplantation. It is usually responsible for unexplained acute and chronic red blood cell aplasia that does not respond to erythropoietin therapy. Cases of parvovirus B19 infection associated with pancytopenia, solid organ dysfunction, and allograft rejection have been described in the literature. The deterioration of the immune system as a result of severe immunotherapy favors the reactivation of a previous infection or the acquisition of a new one. We present a case of a 32-year-old woman with a 1-year history of renal allograft transplant and previous cytomegalovirus (CMV) infection who presented with chest pain, polyarthritis, pancytopenia, and renal dysfunction. A serum sample using polymerase chain reaction showed a parvovirus titer of 13.8 trillion IU/mL and a CMV titer of 800 IU/mL. The renal biopsy revealed nucleomegaly with focal viral inclusions, along with changes associated with immunotherapy toxicity. Electron microscopy demonstrated capillary and tubular epithelial cells with "viral factories," thereby confirming the diagnosis. Thus, screening for parvovirus B19 is advised in high-risk patients who present with refractory anemia to avoid the complications of a chronic infection associated with the fatal rejection of the transplanted organ.

Little is known about the women connected to Indian MSM and their impact on HIV risk. We surveyed 240 Indian MSM, who identified their social networks (n = 7,092). Women (n = 1,321) comprised 16.7 % of the network, with 94.7 % representing non-sexual connections. MSM were classified as having low, moderate, or high female network proportion. MSM with moderate female network proportion (8-24 % total network) had significantly lowered odds of HIV seropositivity (AOR = 0.24, 95 % CI = 0.1-0.6). This suggests moderate proportions of female connections could mediate HIV risk. HIV prevention interventions in India could consider the greater involvement of women among their target audiences. Se sabe poco sobre las mujeres conectadas a HSH en India y su impacto en el riesgo de VIH. Se encuestó a 240 HSH indios, quienes identificaron sus redes sociales (n = 7,092). Las mujeres (n = 1,321) formaron al 16.7 % de la red, del cual el 94.7 % representa conexiones no sexuales. Los HSH se clasificaron como baja, moderada o alta proporción de red femenina. HSH con proporción moderada de red femenina (8-24 % del red total) tuvieron un riesgo significativamente reducido de seropositividad de VIH (AOR = 0,24; IC 95 % = 0,1-0,6). Esto sugiere que tener una proporción moderada de contactos femeninos podría atenuar el riesgo de VIH. Las intervenciones de prevención del VIH en India podrían considerar una mayor participación de las mujeres en su público objetivo.

Studies of HIV prevention interventions such as pre-exposure prophylaxis (PREP) and circumcision in India are limited. The present study sought to investigate Indian truck-drivers initial commitment to PREP and circumcision utilizing the AIDS Risk Reduction Model. Ninety truck-drivers completed an in-depth qualitative interview and provided a blood sample for HIV and HSV-2 testing. Truck-drivers exhibited low levels of initial commitment towards PREP and even lower for circumcision. However, potential leverage points for increasing commitment were realized in fear of infecting family rather than self, self-perceptions of risk, and for PREP focusing on cultural beliefs towards medication and physicians. Cost was a major barrier to both HIV prevention interventions. Despite these barriers, our findings suggest that the ARRM may be useful in identifying several leverage points that may be used by peers, health care providers and public health field workers to enhance initial commitment to novel HIV prevention interventions in India.

Introduction: Invasive candidiasis and candidemia are life-threatening nosocomial infections in intensive care patients., Methods: A post hoc analysis of a phase 3 trial assessing micafungin (100 mg/day for subjects > 40 kg; 2 mg/kg/day for subjects

Background: Sentinel surveillance conducted in the high Human Immuno-deficiency Virus (HIV) prevalent state of Andhra Pradesh includes sub-populations thought to be at high-risk for HIV, but has not included truck drivers. Novel HIV prevention programs targeting this population increasingly adopt public - private partnership models. There have been no targeted studies of HIV prevalence and risk behavior among truck drivers belonging to the private sector in India., Methods: A sample of 189 truck drivers, aged between 15 and 56, were recruited from Gati Limited's large trucking depot in Hyderabad, India. A quantitative survey instrument was conducted along with blood collection for HIV 1/2 testing. Multivariate regression models were utilized to determine predictors of HIV infection and risk behavior., Results: 2.1% of subjects were infected with HIV. Older age was protective against self-reported genital symptoms (OR = 0.77; P = 0.03), but these were more likely among those truck drivers with greater income (OR = 1.05; P = 0.02), and those who spent more time away from home (OR = 25.7; P = 0.001). Men with higher incomes also reported significantly more sex partners (OLS coefficient = 0.016 more partners / 100 rupees in monthly income, P = 0.04), as did men who spent a great deal of time away from home (OLS coefficient = 1.30, P = 0.002). Drivers were more likely to report condom use with regular partners if they had ever visited a female sex worker (OR = 6.26; P = 0.002), but married drivers exhibited decreased use of condoms with regular partners (OR = 0.14, P = 0.008). Men who had higher levels of knowledge regarding HIV and HIV preventative practices were also more likely to use condoms with regular partners (OR = 1.22, P = 0.03)., Conclusion: Time away from home, urban residence, income, and marital status were the strongest correlates of genital symptoms for Sexually Transmitted Infections (STI) and risk behaviors, although none were consistent predictors of all outcomes. Low HIV prevalence might be explained by a cohort that was mostly married, and at home. Novel HIV prevention interventions may be most cost effective when focusing upon young, single, and long-haul truck drivers.

Peroxisome proliferator activated-receptor (PPAR) isoforms, alpha and gamma, function as important coregulators of energy (lipid) homeostasis. PPARalpha regulates fatty acid oxidation primarily in liver and to a lesser extent in adipose tissue, whereas PPARgamma serves as a key regulator of adipocyte differentiation and lipid storage. Of the two PPARgamma isoforms, PPARgamma1 and PPARgamma2 generated by alternative splicing, PPARgamma1 isoform is expressed in liver and other tissues, whereas PPARgamma2 isoform is expressed exclusively in adipose tissue where it regulates adipogenesis and lipogenesis. Since the function of PPARgamma1 in liver is not clear, we have, in this study, investigated the biological impact of overexpression of PPARgamma1 in mouse liver. Adenovirus-PPARgamma1 injected into the tail vein induced hepatic steatosis in PPARalpha(-/-) mice. Northern blotting and gene expression profiling results showed that adipocyte-specific genes and lipogenesis-related genes are highly induced in PPARalpha(-/-) livers with PPARgamma1 overexpression. These include adipsin, adiponectin, aP2, caveolin-1, fasting-induced adipose factor, fat-specific gene 27 (FSP27), CD36, Delta(9) desaturase, and malic enzyme among others, implying adipogenic transformation of hepatocytes. Of interest is that hepatic steatosis per se, induced either by feeding a diet deficient in choline or developing in fasted PPARalpha(-/-) mice, failed to induce the expression of these PPARgamma-regulated adipogenesis-related genes in steatotic liver. These results suggest that a high level of PPARgamma in mouse liver is sufficient for the induction of adipogenic transformation of hepatocytes with adipose tissue-specific gene expression and lipid accumulation. We conclude that excess PPARgamma activity can lead to the development of a novel type of adipogenic hepatic steatosis.

Purpose: In a randomized, double-blind, comparative, multicenter trial, liposomal amphotericin B was equivalent to conventional amphotericin B for empirical antifungal therapy in febrile neutropenic patients, using a composite end point, but was more effective in reducing proven emergent fungal infections, infusion-related toxicities, and nephrotoxicity. The purpose of this study was to compare the pharmacoeconomics of liposomal versus conventional therapy., Patients and Methods: Itemized hospital billing data were collected on 414 patients from 19 of the 32 centers that participated in the trial. Hospital length of stay and costs from the first dose of study medication to the time of hospital discharge were assessed., Results: Hospital costs from the time of first dose to discharge were significantly higher for all patients who received liposomal amphotericin B ($48,962 v $43,183; P =.022). However, hospital costs were highly sensitive to the cost of study medication ($39,648 v $43,048 when drug costs were not included; P =.416). Using decision analysis models and sensitivity analyses to vary the cost of study medications and the risk of nephrotoxicity, the break-even points for the cost of liposomal therapy were calculated to range from $72 to $87 per 50 mg for all patients and $83 to $112 per 50 mg in allogeneic bone marrow transplant patients., Conclusion: The cost of liposomal amphotericin B and patient risk for developing nephrotoxicity play large roles in determining whether liposomal amphotericin B is cost-effective as first-line empirical therapy in persistently febrile neutropenic patients.

Mucormycosis is an infection caused by a group of fungi in the order Mucorales in the phylum Zygomycota. The most well-known form of this disease is rhinocerebral mucormycosis, which usually develops in diabetic or immunocompromised patients. The fungal hyphal elements are easily detected in biopsy specimens by direct or histologic examination. However, the confirmatory identification of the genus or species requires culture of the specimen. This article presents a case of rhinocerebral mucormycosis in which presumptive identification of the genus was made without microbiologic cultures and was based on the extraordinarily rare appearance of fungal sporangia and sporangiospores in histologic tissue sections. Identification of these structures allowed an early and accurate diagnosis of rhinocerebral invasive mucormycosis.

The safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) administered for empirical antifungal therapy were evaluated for 36 persistently febrile neutropenic adults receiving cancer chemotherapy and bone marrow transplantation. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study which enrolled a total of 8 to 12 patients in each of the four dosage cohorts. Each cohort received daily doses of either 1.0, 2.5, 5.0, or 7.5 mg of amphotericin B in the form of AmBisome/kg of body weight. The study population consisted of patients between the ages of 13 and 80 years with neutropenia (absolute neutrophil count, <500/mm3) who were eligible to receive empirical antifungal therapy. Patients were monitored for safety and tolerance by frequent laboratory examinations and the monitoring of infusion-related reactions. Efficacy was assessed by monitoring for the development of invasive fungal infection. The pharmacokinetic parameters of AmBisome were measured as those of amphotericin B by high-performance liquid chromatography. Noncompartmental methods were used to calculate pharmacokinetic parameters. AmBisome administered as a 1-h infusion in this population was well tolerated and was seldom associated with infusion-related toxicity. Infusion-related side effects occurred in 15 (5%) of all 331 infusions, and only two patients (5%) required premedication. Serum creatinine, potassium, and magnesium levels were not significantly changed from baseline in any of the dosage cohorts, and there was no net increase in serum transaminase levels. AmBisome followed a nonlinear dosage relationship that was consistent with reticuloendothelial uptake and redistribution. There were no breakthrough fungal infections during empirical therapy with AmBisome. AmBisome administered to febrile neutropenic patients in this study was well tolerated, was seldom associated with infusion-related toxicity, was characterized by nonlinear saturation kinetics, and was effective in preventing breakthrough fungal infections.

A total of four cytomegalovirus (CMV) isolates were obtained from two CMV seronegative patients, each of whom received a lung transplant from the same seropositive donor. CMV was isolated from Patient 1 from two bronchial alveolar lavage (BAL) specimens, one obtained during treatment with ganciclovir (GCV) and a second during later treatment with foscarnet. Both of these isolates are sensitive to GCV and foscarnet. CMV was isolated from Patient 2 from a blood and a BAL specimen obtained during treatment with GCV. Both of these isolates are resistant to GCV and show reduced GCV phosphorylation. Patient 1 is still alive 33 months posttransplant. Patient 2 died 6 1/2 months posttransplant. Although the four strains differ with respect to GCV susceptibility and phosphorylation, their DNA restriction fragment hybridization patterns and UL97 kinase gene sequences indicate that they are closely related. The restriction fragment hybridization patterns are identical among the strains, while these patterns differ markedly from those of unrelated strains. The DNA sequences of the UL97 genes of the strains from Patient 2 differ by only one nucleotide from those of Patient 1. The same comparison with unrelated strains shows a minimum of 12 nucleotide differences. The nucleotide change in the strains from Patient 2 produces an amino acid substitution of serine for leucine at residue 595, a substitution that was previously shown to transfer GCV resistance. Both patients, therefore, were apparently infected with the same donor strain, but during the course of GCV prophylaxis and treatment, a GCV-resistant mutant strain was selected in Patient 2.

Lung transplantation is now an accepted modality for treating end-stage lung disease. To better understand the factors limiting the survival of these patients, we reviewed the autopsy findings in 37 patients who received lung transplants. Between 1986 and 1995, 131 patients have undergone lung transplantation at our institution, including 4 patients with repeat transplantations. Of these, 48 (36.6%) died, 37 (77%) of whom had an autopsy. The autopsied patients were divided into three groups on the basis of post-transplantation interval: early (< 30 d), intermediate (31-365 d), and late (> 365 d). Of the 12 patients in the early group, 6 died of intra- and postoperative complications and 6 of bacterial infection with pneumonia in the transplanted lung. There were 18 patients in the intermediate group, of whom 11 died of infection (5 of cytomegalovirus, 5 of nonviral infections of the transplanted lung, and 1 of encephalomyelitis), 3 of post-transplantation lymphoproliferative disorder, 3 of chronic airway rejection, and one of unrelated cause. Of the seven patients in the late group, four died of chronic airway rejection, two of unrelated causes, and one of bacterial infection. Native lungs examined in 23 patients showed, in addition to the primary disease, bacterial pneumonia in 5, post-transplantation lymphoproliferative disorder in 3, cytomegalovirus in 2, and aspergillosis in 1. In this series of 37 autopsied patients, chronic rejection was the cause of death in 7 and was concomitantly seen in 3 patients (27%). In summary, the most common cause of death was infection (48%), followed by chronic rejection (19%), surgical complications (19%), post-transplantation lymphoproliferative disorder (7%), and unrelated causes (7%); rejection was not a major cause of death in the early and intermediate post-transplantation periods; in 30% of native lungs, significant pathologic findings were present in addition to the primary disease; and in the intermediate post-transplantation period, significant left ventricular hypertrophy occurred, which may be attributable to cyclosporine-induced hypertension but which needs to be further studied.

Background: Aspergillus infection is a known complication of transplantation., Methods: We describe our experience with 37 patients who received lung transplants over 2 years at Loyola University Medical Center. All patients who had evidence of aspergillus on culture of clinical specimens or had biopsies with hyphal forms consistent with aspergillus were categorized according to the clinical manifestations. Important risk factors were analyzed in comparison with other lung transplant recipients during the same period., Results: The incidence of invasive aspergillosis was high (16%). No patient with disseminated disease survived. Locally invasive disease responded well to treatment with amphotericin B and itraconazole., Conclusions: Lung transplantation patients may have a higher incidence of aspergillosis as compared with other transplantation groups. Prophylactic measures need to be explored.

Infections are the most common cause of early and late morbidity and mortality in lung transplant recipients. Viral infections, in particular, have been linked to acute rejection, chronic rejection, and development of lymphoproliferative diseases.

Nucleotide sequences of portions of second and fifth exons of urate oxidase encoding gene (UOX) of chimpanzee, gorilla, orangutan, rhesus monkey and squirrel monkey obtained following amplification by polymerase chain reaction have been compared with corresponding sequences of human, baboon and rat UOX. Two or more nonsense mutations are found in the coding regions of this UOX gene thus far analyzed in human, chimpanzee, gorilla and orangutan, but not in the baboon, rhesus monkey and squirrel monkey. Of these nonsense mutations, the stop codon at amino acid position 33 is constant in the human and the three great apes suggesting that this may be the original mutation responsible for the inactivation of the UOX gene during hominoid evolution.