Immunosuppression in liver transplantation: beyond calcineurin inhibitors.

Although calcineurin inhibitors (CNIs) remain the mainstay of immunosuppression in liver transplantation (LTX), their long-term toxicity significantly contributes to morbidity and mortality. The elucidation of mechanisms of alloimmunity and leukocyte migration have provided novel targets for immunosuppression development. The toxicities of these agents differ from that of the CNI and act additively or synergistically. CNI avoidance protocols in LTX have not been achieved routinely; however, pilot trials have begun to delineate the limitations and promises of such approaches. CNI-sparing protocols appear to be much more promising in balancing the early need for minimizing rejection while tapering doses and minimizing long-term toxicity.     

Carcinoid tumors of the lung: a diagnostic challenge in bronchial washings

Bronchial washings are used routinely in the diagnosis of lung tumors. However, unlike other tumors, the diagnosis of bronchial carcinoids on bronchial washings is difficult. We reviewed 17 cases of histologically proven bronchial carcinoids from the files of the cytology laboratory over a period of 15 yr (1986–2001). The bronchial washings and histology sections of all the cases were reviewed separately by two independent observers and the results tabulated. Two cases had inadequate bronchial washings for evaluation and were excluded from the study. A growth was identified on bronchoscopy in 13 of 15 cases. Initial cytologic diagnoses were ?adenocarcinoma/?carcinoid and suspicious of carcinoid in one case each. However, on review, tumor was identified in 10 of 13 cases initially considered to be negative. The possible reasons for a false‐negative report on initial cytology include the paucity of tumor cell fragments in the bronchial washings (5 of 12 cases showing only one to two tumor fragments) and their bland appearance, often being mistaken for benign columnar cells. This study highlights the potential pitfalls in the diagnosis of bronchial carcinoids on bronchial washings and underlines the importance of a diligent search in cases with high clinical suspicion and positive bronchoscopic findings. Diagn. Cytopathol. 2004;30:62–66. © 2004 Wiley‐Liss, Inc.     

Cytopathology of uncommon malignant renal neoplasms in the pediatric age group

Malignant renal neoplasms are common solid tumors in pediatric oncology practice. These include the common Wilms' tumor/nephroblastoma and the uncommon neoplasms such as clear-cell sarcoma of the kidney (CCSK), rhabdoid tumor, renal-cell carcinoma, and others. The aim of this study was to describe in detail the cytopathological features of the histopathologically proven uncommon pediatric renal tumors. Aspirates from Wilms' tumor, which are mesenchyme predominant, show clusters of spindle cells associated with the matrix material. Evidence of rhabdomyoblastic differentiation may be present. CCSK, classic subtype, is characterized by round to oval cells arranged perivascularly and also in sheets and clusters intimately associated with a metachromatic matrix mucopolysaccharide material better appreciated in May-Grunwald-Giemsa (MGG)-stained smears. The cells also have more abundant cytoplasm and may show nuclear grooves. Spindle-cell pattern of CCSK is difficult to diagnose on aspiration cytology. Renal-cell carcinoma of childhood shows similar cytological features as its adult counterpart. Rhabdoid tumor of the kidney is characterized by a monomorphic population of cells with abundant cytoplasm, eccentric nuclei with prominent nucleoli. Intrarenal yolk sac tumor is a rare neoplasm and shows severely pleomorphic cells on aspiration.Awareness of these entities is important for the practicing cytopathologist. Further, non-Wilms' renal malignant neoplasms must be distinguished from the common Wilms' tumor so that appropriate chemotherapy protocols may be instituted in cases where the tumor is in an advanced stage of malignancy.     

Making a working clinical diagnosis of HIV infection in infants in Zimbabwe

Objectives Clinical algorithms can be helpful in decisions about treatment and feeding options in infancy, but have had limited exposure to real data. This analysis uses data from a large clinical trial to test such algorithms, and thereby develop a successor which performs usefully in poor countries with high HIV‐prevalence. Methods The ZVITAMBO trial followed 14 110 mother‐baby pairs through infancy. 32% of mothers were HIV‐positive. Infants were HIV tested regularly using DNA PCR. Clinical signs were evaluated in terms of identifying HIV‐infection at 6 weeks, 6 and 12 months, using Zimbabwean, South African, and WHO generic adaptations of the WHO integrated management of childhood illness HIV algorithm. A modification, in which HIV‐exposed infants are first divided into being at least or less than median weight‐for‐age, was derived and evaluated. Results At 6 weeks 65% of all infected babies are less than median weight‐for‐age. Adding at least two clinical signs reduces sensitivity to 20% but those identified are 1.5 (95% CI 1.1–2.1) times more likely to die by 6 months than other infected infants. At 6 months, 86% of uninfected babies of HIV‐infected mothers can be identified by selecting those whose weight is greater than median or, if less than median, who exhibit <2 clinical signs. Conclusions In poor settings a simple clinical algorithm can identify children with probable HIV infection, especially those at risk of early death, who can then be referred for further testing and care, including highly active antiretroviral therapy. Most infants who are HIV‐uninfected can be identified at 6 months and provided with support to maintain infection‐free survival, including focussed infant‐feeding counselling.     

Nanocarrier-based interventions for the management of MDR/XDR-TB

Emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB over the past decade presents an unprecedented public health challenge to which countries of concern are responding far too slowly. Global Tuberculosis Report 2014 marks the 20th anniversary of the Global Project on Anti-Tuberculosis Drug Resistance Surveillance, indicating the highest global level of drug-resistance ever recorded detection of 97?000 patients with MDR-TB resulting in 170?000 deaths in 2013. Treatment of MDR-TB is expensive, complex, prolonged (18–24 months) and associated with a higher incidence of adverse events. In this context, nanocarrier delivery systems (NDSs) efficiently encapsulating considerable amounts of second-line anti tubercular drugs (^sATDs), eliciting controlled, sustained and more profound effect to trounce the need to administer ^sATDs at high and frequent doses, would assist in improving patient compliance and avoid hepatotoxicity and/or nephrotoxicity/ocular toxicity/ototoxicity associated with the prevalent ^sATDs. Besides, NDSs are also known to inhibit the P-glycoprotein efflux, reduce metabolism by gut cytochrome P-450 enzymes and circumnavigate the hepatic first-pass effect, facilitating absorption of drugs via intestinal lymphatic pathways. This review first provides a holistic account on MDR-TB and discusses the molecular basis of Mycobacterium tuberculosis resistance to anti-tubercular drugs. It also provides an updated bird’s eye view on current treatment strategies and laboratory diagnostic test for MDR-TB. Furthermore, a relatively pithy view on patent studies on second-line chemotherapy using NDSs will be discussed.     

Experience with similar biologic rituximab in 77 patients of granulomatosis with polyangiitis—a real-life experience

Clinical Rheumatology - To present single centre experience on the efficacy and safety of similar biologic of rituximab in patients with granulomatosis with polyangiitis (GPA). This was a...