A Comprehensive Analysis of 174 Febrile Patients Admitted to Okayama University Hospital

Primary care physicians often encounter patients with fever of unknown origin and without apparent causes. Recent advances in laboratory medicine have facilitated diagnostic procedures;however, it is still difficult to determine the critical febrile factor at an early stage. We reviewed the medical records of 174 patients who were admitted due to a chief complaint of fever (＞37.5℃) to our hospital during the period from 2004 to 2010. The patients were categorized into patients with infection, inflammation, neoplasm and drug-induced fever. Based on the analysis done by category, it was revealed that the patient's age, body temperature and duration of fever were closely related to the final diagnosis. Serum CRP levels were significantly low in the nonbacterial infection group, while serum levels of sIL-2R were high in neoplasm and drug-induced cases. CRP level on admission was weakly but significantly correlated with body temperature, while duration of fever was inversely related to body temperature. The effectiveness of PET-CT and tissue biopsy for diagnosis was considerably high, particularly in the categories of neoplasm and nonspecific inflammation, respectively, though the effectiveness of bacterial culture was low. Thus, a careful review of physical and laboratory information including body temperature, CRP level, duration of fever, gender difference and history of medication is indispensable for diagnosis. Stepwise categorization and disease classification by comprehensive and systemic checkup are very helpful for determining the causes of fever

Immunorestitution disease involving the innate and adaptive response

Immunorestitution disease (IRD) is defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection that is temporally related to the recovery of the immune system. We report the temporal sequence of events that led to IRD caused by Pneumocystis carinii and Aspergillus terreus in 2 human immunodeficiency virus (HIV)-negative patients soon after the recovery of adaptive and innate immunity, respectively, and we review episodes noted in the English-language literature that fit the definition of IRD (109 episodes in 107 patients). The median time from the recovery of neutrophil counts or termination of steroid therapy to the development of IRD was 8 days in cases of pulmonary aspergillosis (23 episodes) and hepatosplenic candidiasis (8) and 21 days for viral diseases such as hepatitis B (24) and viral pneumonitis (6). For IRD due to mycobacteriosis (27 episodes) and cryptococcosis (4) in HIV-positive patients, the median interval between the initiation of highly active antiretroviral therapy (HAART) and the onset of IRD was 11 days; for viral infections, including those due to cytomegalovirus (14), hepatitis B virus (1), and hepatitis C virus (2), the median interval was 42 days. As an emerging clinical entity, IRD merits further study to optimize treatment of immunosuppressed patients.published_or_final_versio

Diagnostic virology.

Diagnostic virology services are increasingly available and pertinent as the number of useful antiviral agents grows. In this article, current methods of diagnosis are reviewed with special emphasis on rapid procedures. Guidelines for interpretation of cultures and other tests are provided

In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation.

Regulatory T cells (Tregs) have been shown to be critical in the balance between autoimmunity and tolerance and have been implicated in several human autoimmune diseases. However, the small number of Tregs in peripheral blood limits their therapeutic potential. Therefore, we developed a protocol that would allow for the expansion of Tregs while retaining their suppressive activity. We isolated CD4+CD25 hi cells from human peripheral blood and expanded them in vitro in the presence of anti-CD3 and anti-CD28 magnetic Xcyte Dynabeads and high concentrations of exogenous Interleukin (IL)-2. Tregs were effectively expanded up to 200-fold while maintaining surface expression of CD25 and other markers of Tregs: CD62L, HLA-DR, CCR6, and FOXP3. The expanded Tregs suppressed proliferation and cytokine secretion of responder PBMCs in co-cultures stimulated with anti-CD3 or alloantigen. Treg expansion is a critical first step before consideration of Tregs as a therapeutic intervention in patients with autoimmune or graft-versus-host disease

Macaque models of human infectious disease.

Macaques have served as models for more than 70 human infectious diseases of diverse etiologies, including a multitude of agents-bacteria, viruses, fungi, parasites, prions. The remarkable diversity of human infectious diseases that have been modeled in the macaque includes global, childhood, and tropical diseases as well as newly emergent, sexually transmitted, oncogenic, degenerative neurologic, potential bioterrorism, and miscellaneous other diseases. Historically, macaques played a major role in establishing the etiology of yellow fever, polio, and prion diseases. With rare exceptions (Chagas disease, bartonellosis), all of the infectious diseases in this review are of Old World origin. Perhaps most surprising is the large number of tropical (16), newly emergent (7), and bioterrorism diseases (9) that have been modeled in macaques. Many of these human diseases (e.g., AIDS, hepatitis E, bartonellosis) are a consequence of zoonotic infection. However, infectious agents of certain diseases, including measles and tuberculosis, can sometimes go both ways, and thus several human pathogens are threats to nonhuman primates including macaques. Through experimental studies in macaques, researchers have gained insight into pathogenic mechanisms and novel treatment and vaccine approaches for many human infectious diseases, most notably acquired immunodeficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV). Other infectious agents for which macaques have been a uniquely valuable resource for biomedical research, and particularly vaccinology, include influenza virus, paramyxoviruses, flaviviruses, arenaviruses, hepatitis E virus, papillomavirus, smallpox virus, Mycobacteria, Bacillus anthracis, Helicobacter pylori, Yersinia pestis, and Plasmodium species. This review summarizes the extensive past and present research on macaque models of human infectious disease

Temporal Changes in Routine Health Markers and Their Association with Illness and Mortality Rates in Cats Naturally Infected with Feline Immunodeficiency Virus

Feline immunodeficiency virus is an important lentiviral infection in cats. Infection is life-long and results in immune compromise, increased susceptibility to opportunistic infections and early mortality. Infection is commonly referred to in three stages: acute, (asymptomatic) and end stage (symptomatic); although not all cats will progress to end stage disease. Acute infection lasts several months during which cats may have mild, transient anorexia, lethargy, fever, lymphadenomegaly and diarrhea. There is loss of mucosal and peripheral CD4 T cells, expansion of a subset of CD8 T cells, CD8βlow, and establishment of viremia during this period. Asymptomatic infection lasts a variable period of years during which progressive decreases in CD4 T cells and inversion of the CD4:CD8 ratio occurs. End stage infection does not occur in all infected cats. It is characterized by a rapid decline in health including generalized muscle wasting, treatment-refractory opportunistic infection and / or neoplasia leading to death within months. A marked decrease in CD4 T cell counts and CD4:CD8 ratio and several fold increase in viremia occurs during end stage disease but reported literature is sparse. Longitudinal studies of specific pathogen free cats experimentally infected with FIV infection have focused primarily on acute and early asymptomatic stages of infection. Little has been reported on the transition from late chronic to end stage disease. Longitudinal studies of cats naturally infected with FIV are needed to better characterize the course of infection

Human herpesvirus 6: An emerging pathogen.

Infections with human herpesvirus 6 (HHV-6), a beta-herpesvirus of which two variant groups (A and B) are recognized, is very common, approaching 100% in seroprevalence. Primary infection with HHV-6B causes roseola infantum or exanthem subitum, a common childhood disease that resolves spontaneously. After primary infection, the virus replicates in the salivary glands and is shed in saliva, the recognized route of transmission for variant B strains; it remains latent in lymphocytes and monocytes and persists at low levels in cells and tissues. Not usually associated with disease in the immunocompetent, HHV-6 infection is a major cause of opportunistic viral infections in the immunosuppressed, typically AIDS patients and transplant recipients, in whom HHV-6 infection/reactivation may culminate in rejection of transplanted organs and death. Other opportunistic viruses, human cytomegalovirus and HHV-7, also infect or reactivate in persons at risk. Another disease whose pathogenesis may be correlated with HHV-6 is multiple sclerosis. Data in favor of and against the correlation are discussed