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Biomedical subjects

Kevin C Kain

Publications and source records attributed to Kevin C Kain.

At least 19 recordsLinked to original sources
PubMed2005

Entamoeba histolytica: identification of a distinct beta2 integrin-like molecule with a potential role in cellular adherence.

Entamoeba histolytica infection causes dysentery, intestinal colitis, and hepatic abscess in an estimated 50 million people worldwide. Attachment of E. histolytica trophozoites to intestinal epithelium and vascular endothelium during liver metastasis results in an inflammatory process. We report the identification of a distinct amebic beta2 integrin (CD18)-like molecule which affords adherence to TNF-alpha-activated endothelial cells. Data from flow cytometry and indirect immunofluorescence assays suggest the amebic beta2 integrin was localized to focal adhesion plates and was present in both E. histolytica and Entamoeba dispar. The amebic beta2 integrin appeared to be distinct from the amebic Gal/GalNAc lectin based on recombinant expression, amebic colocalization, and ELISA studies. Trophozoite adherence to endothelial cells expressing ICAM-1 (CD54) following activation with TNF-alpha or ICAM-1-transfected CHO cells was specifically inhibited with anti-CD18 or anti-CD54 MAbs. In summary, evidence in support of a distinct beta2 integrin-like molecule participating in amebic adherence to TNF-alpha-activated endothelial cells expressing ICAM-1 is presented. The presence of integrin-dependent binding may allow trophozoites to opportunistically adhere to activated intestinal epithelium or vascular endothelium expressing ICAM-1 during amebic colitis or hepatic abscess.

Animals↗
PubMed2005

Peroxisome proliferator-activated receptor gamma and retinoid X receptor agonists have minimal effects on the interaction of endothelial cells with Plasmodium falciparum-infected erythrocytes.

Peroxisome proliferator-activated receptor gamma-retinoid X receptor (PPARgamma-RXR) agonists had minimal effects on the surface levels of CD36, intercellular cell adhesion molecule-1, or platelet-endothelial cell adhesion molecule-1 and had no effect on the cytoadherence of infected erythrocytes to either human umbilical vein endothelial cells or human microvascular endothelial cells or on malaria-induced interleukin-6 secretion from these cells. PPARgamma-RXR agonists do not significantly modify malaria-infected erythrocyte-endothelial cell interactions in vitro.

Animals↗
PubMed2004

Fatal severe acute respiratory syndrome is associated with multiorgan involvement by coronavirus.

Severe acute respiratory syndrome (SARS) is characterized by pulmonary compromise; however, patients often have evidence of other organ dysfunction that may reflect extrapulmonary dissemination of SARS coronavirus (SARS-CoV). We report on the distribution and viral load of SARS-CoV in multiple organ samples from patients who died of SARS during the Toronto outbreak. SARS-CoV was detected in lung (100%), bowel (73%), liver (41%), and kidney (38%) in 19 patients who died of SARS, with the highest viral loads observed in lung (1.0 x 10(10) copies/g) and bowel (2.7 x 10(9) copies/g). Fatal SARS was associated with multiorgan viral dissemination in a distribution that has implications for disease manifestation, viral shedding, and transmission.

Coronavirus↗
PubMed2004

Tropical pulmonary eosinophilia: a case series in a setting of nonendemicity.

BACKGROUND: Tropical pulmonary eosinophilia (TPE) is a rare but serious manifestation of infection with the lymphatic filarial parasites Wuchereria bancrofti and Brugia malayi. Although endemicity is limited to the tropical and subtropical regions of Africa, South America, and Asia, immigration and travel practices have led to the diagnosis of TPE in areas of nonendemicity. METHODS: We herein present a case series of all patients with TPE who presented to the Toronto General Hospital during 1990-2003. RESULTS: Seventeen individuals presented with TPE during the study period, and all were of South Asian ancestry. All 17 received an incorrect diagnosis at presentation (median number of consultations before diagnosis, 2), the most frequent of which was asthma (76%). Eosinophil count, serum immunoglobulin E levels, and anti-filarial antibody titers were elevated in all patients. Ten of 14 patients had an abnormal chest radiograph finding, and 11 of 12 patients had abnormal results of pulmonary function tests. CONCLUSIONS: TPE is an important diagnostic consideration in patients with eosinophilia, respiratory symptoms, and history of exposure to this disease. In the untreated individual, TPE can lead to chronic and progressive respiratory compromise and death. Prompt recognition and treatment with diethylcarbamazine is therefore key to minimizing morbidity and mortality.

Adolescent↗
PubMed2004

Malaria in travelers: a review of the GeoSentinel surveillance network.

BACKGROUND: Malaria is a common and important infection in travelers. METHODS: We have examined data reported to the GeoSentinel surveillance network to highlight characteristics of malaria in travelers. RESULTS: A total of 1140 malaria cases were reported (60% of cases were due to Plasmodium falciparum, 24% were due to Plasmodium vivax). Male subjects constituted 69% of the study population. The median duration of travel was 34 days; however, 37% of subjects had a travel duration of < or =4 weeks. The majority of travellers did not have a pretravel encounter with a health care provider. Most cases occurred in travelers (39%) or immigrants/refugees (38%). The most common reasons for travel were to visit friends/relatives (35%) or for tourism (26%). Three-quarters of infections were acquired in sub-Saharan Africa. Severe and/or complicated malaria occurred in 33 cases, with 3 deaths. Compared with others in the GeoSentinel database, patients with malaria had traveled to sub-Saharan Africa more often, were more commonly visiting friends/relatives, had traveled for longer periods, presented sooner after return, were more likely to have a fever at presentation, and were less likely to have had a pretravel encounter. In contrast to immigrants and visitors of friends or relatives, a higher proportion (73%) of the missionary/volunteer group who developed malaria had a pretravel encounter with a health care provider. Travel to sub-Saharan Africa and Oceania was associated with the greatest relative risk of acquiring malaria. CONCLUSIONS: We have used a global database to identify patient and travel characteristics associated with malaria acquisition and characterized differences in patient type, destinations visited, travel duration, and malaria species acquired.

Africa↗
PubMed2004

Complicated and fatal Strongyloides infection in Canadians: risk factors, diagnosis and management.

Strongyloidiasis, which is caused by the nematode Strongyloides stercoralis, is a common and persistent infection, particularly in developing countries. In the setting of compromised cellular immunity, it can result in fulminant dissemination with case-fatality rates of over 70%. The majority of new Canadian immigrants come from countries where Strongyloides is highly endemic; therefore, the burden of Strongyloides may be underappreciated in Canada. Because early diagnosis and therapy can have a marked impact on disease outcome, screening for this infection should be considered mandatory for patients who have a history of travel or residence in a disease-endemic area and risk factors for disseminated disease (e.g., corticosteroid use and human T-lymphotropic virus type I infection).

Animals↗
PubMed2004

Inactivation of Plasmodium falciparum by photodynamic excitation of heme-cycle intermediates derived from delta-aminolevulinic acid.

Transfusion-transmitted malaria (TTM), especially that caused by Plasmodium falciparum, is of great concern in malaria-endemic areas. As a result of increased international travel, migration, and the spread of drug-resistant parasites, TTM is also a growing problem in industrialized nations. An effective and inexpensive means of inactivating malaria parasites in blood products would represent an important advance. In this report, we demonstrate that photoactivation of plasmodial heme-cycle intermediates, derived from supplemental delta -aminolevulinic acid (ALA), by exposure to simple white light in the presence of ALA, reduces P. falciparum in culture to levels that are undetectable by light microscopy or lactate dehydrogenase assay. Photodynamic excitation of presumed heme-cycle intermediates, which was revealed by fluorescence microscopy, did not appear to adversely affect the viability of erythrocytes. These data suggest that this pathogen-inactivation strategy, which uses inexpensive reagents and white light, may represent an appropriate means of inactivating malaria parasites in blood products in resource-poor settings.

Aminolevulinic Acid↗
PubMed2004

Malaria.

Malaria is a parasitic infection of global importance. Although relatively uncommon in developed countries, where the disease occurs mainly in travellers who have returned from endemic regions, it remains one of the most prevalent infections of humans worldwide. In endemic regions, malaria is a significant cause of morbidity and mortality and creates enormous social and economic burdens. Current efforts to control malaria focus on reducing attributable morbidity and mortality. Targeted chemoprophylaxis and use of insecticide-treated bed nets have been successful in some endemic areas. For travellers to malaria-endemic regions, personal protective measures and appropriate chemoprophylaxis can significantly reduce the risk of infection. Prompt evaluation of the febrile traveller, a high degree of suspicion of malaria, rapid and accurate diagnosis, and appropriate antimalarial therapy are essential in order to optimize clinical outcomes of infected patients. Additional approaches to malaria control, including genetic manipulation of mosquitoes and malaria vaccines, are areas of ongoing research.

Anemia↗
PubMed2004

CD36 mediates the phagocytosis of Plasmodium falciparum-infected erythrocytes by rodent macrophages.

Phagocytic cells represent an important line of innate defense against malaria; however, little is known of the mechanism by which macrophages recognize Plasmodium falciparum-parasitized erythrocytes (PEs). Using macrophages from CD36 wild-type (WT), CD36-null, and CD36 transgenically-rescued rodents, we demonstrate a major role for CD36 in the phagocytosis of PEs. WT macrophages display enhanced phagocytic capacity for nonopsonized PEs, compared with that for CD36-null mouse and rat macrophages. Transgenic rescue of CD36-deficient rats restored macrophage phagocytic capacity for PEs. CD36 receptor blockade with monoclonal antibodies and proteolytic cleavage of CD36 ligands from the surface of PEs inhibited the uptake of PEs. Up-regulation of rodent CD36 by use of peroxisome proliferator-activated receptor (PPARgamma) agonists increased the phagocytosis of PEs. CD36-mediated uptake of PEs did not result in increased tumor necrosis factor-alpha secretion, of which high levels are associated with adverse outcomes in malaria. These studies support the use of these rodent models to examine PE-CD36 interactions.

Animals↗
PubMed2004

Leprosy in Toronto: an analysis of 184 imported cases.

BACKGROUND: Leprosy is a rare but serious mycobacterial infection. Immigration from areas where the disease is endemic has resulted in the importation of leprosy into countries where it is not endemic and where physicians and health care workers have little or no experience in diagnosis and therapy. In this study we characterized leprosy patients seen in a tropical disease unit that manages most of the reported leprosy cases in Canada. METHODS: We reviewed the clinical records of all 184 leprosy patients who were referred to the Tropical Disease Unit at Toronto General Hospital between 1979 and 2002 and abstracted demographic and clinical information. RESULTS: Patients were more likely to be male (122 or 66.3%) and of Indian (44 or 23.9%), Filipino (49 or 26.6%) or Vietnamese (37 or 20.1%) origin. Patients experienced symptoms for a mean of 4.8 years before referral to the Tropical Disease Unit. Most had no family history of leprosy (152/172 or 88.4%). Most patients presented with either borderline tuberculoid (80 or 43.5%) or borderline lepromatous (37 or 20.1%) disease. On average, patients presented with 5.8 skin lesions. Upper- and lower-extremity nerve dysfunction was common at presentation, with up to one-third of patients demonstrating either sensory or motor loss. A significantly greater lag time to presentation was observed in patients who emigrated from low-prevalence regions (p < 0.001). INTERPRETATION: Leprosy is a chronic infectious disease that is associated with serious morbidity if left untreated. Leprosy is uncommon in developed countries, but it is important for physicians to have a high index of suspicion when a foreign-born patient presents with chronic dermatitis and peripheral nerve involvement.

Adult↗
PubMed2004

Leprosy: a primer for Canadian physicians.

Leprosy is a rare but serious infectious disease caused by Mycobacterium leprae. While global prevalence of the disease is decreasing, increasing rates of immigration from countries where leprosy is endemic have led to the recognition of this illness in North America. Classically, leprosy presents as hypopigmented cutaneous macules along with sensory and motor peripheral neuropathies, although the clinical manifestations vary along a disease spectrum. In addition to primary infection, patients may undergo a "reaction," an acute inflammatory response to the mycobacterium, which leads to pain and erythema of skin lesions and dangerous neuritis. Reactions can occur at any time during the course of leprosy, but they tend to be precipitated by treatment. They are a significant cause of impaired quality of life due to marked nerve damage and thus warrant prompt intervention. Although leprosy may have a protracted onset and be difficult to recognize, cure is achievable with appropriate multidrug therapy. Because untreated leprosy can result in permanent, irreversible nerve damage and secondary transmission, early diagnosis and treatment are essential to minimize morbidity.

Diagnosis, Differential↗
PubMed2004

Serial nosocomial transmission of Plasmodium falciparum malaria from patient to nurse to patient.

BACKGROUND: Nosocomial transmission of malaria is a rare phenomenon in the United States. OBJECTIVE: To describe the probable transmission of Plasmodium falciparum malaria from a patient to a healthcare worker and then from the healthcare worker to another patient. DESIGN: Case series. SETTING: Two community hospitals in Massachusetts. INTERVENTION: Routine medical and supportive care. MEASUREMENTS: Clinical and laboratory evaluation. RESULTS: A nurse developed falciparum malaria after a needlestick injury from a patient with documented falciparum malaria. Three days prior to her diagnosis, she cared for another patient, who subsequently developed falciparum malaria. That patient's parasite isolate genetically matched the nurse's isolate by two independent DNA fingerprinting techniques. CONCLUSION: After extensive evaluation, we believe that a nurse who had acquired falciparum malaria via needlestick subsequently transmitted malaria to another patient via a break in standard precautions. The implications of this mechanism of transmission are discussed.

Adult↗
PubMed2004

Evaluation of the RealArt Malaria LC real-time PCR assay for malaria diagnosis.

PCR-based methods have advantages over traditional microscopic methods for the diagnosis of malaria, especially in cases of low parasitemia and mixed infections. However, current PCR-based assays are often labor-intensive and not readily quantifiable and have the potential for contamination due to a requirement for postamplification sample handling. Real-time PCR can address these limitations. This study evaluated the performance characteristics of a commercial malaria real-time PCR assay (RealArt Malaria LC Assay; Artus GmbH, Hamburg, Germany) on the LightCycler platform for the detection of malaria parasites in 259 febrile returned travelers. Compared to nested PCR as the reference standard, the real-time assay had a sensitivity of 99.5%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 99.6% for the detection of malaria. Our results indicate that the RealArt assay is a rapid (<45 min), sensitive, and specific method for the detection of malaria in returned travelers.

Animals↗
PubMed2004

Severe acute respiratory syndrome-associated coronavirus in lung tissue.

Efforts to contain severe acute respiratory syndrome (SARS) have been limited by the lack of a standardized, sensitive, and specific test for SARS-associated coronavirus (CoV). We used a standardized reverse transcription-polymerase chain reaction assay to detect SARS-CoV in lung samples obtained from well-characterized patients who died of SARS and from those who died of other reasons. SARS-CoV was detected in all 22 postmortem lung tissues (to 10(9) viral copies/g) from 11 patients with probable SARS but was not detected in any of the 23 lung control samples (sample analysis was blinded). The sensitivity and specificity (95% confidence interval) were 100% (84.6% to 100%) and 100% (85.1% to 100%), respectively. Viral loads were significantly associated with a shorter course of illness but not with the use of ribavirin or steroids. CoV was consistently identified in the lungs of all patients who died of SARS but not in control patients, supporting a primary role for CoV in deaths.

Adult↗
PubMed2003

Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study.

CONTEXT: Severe acute respiratory syndrome (SARS) is a new clinical entity for which no effective therapeutic strategy has been developed. OBJECTIVE: To provide preliminary results on the potential therapeutic benefit and tolerability of interferon alfacon-1 plus corticosteroids for SARS. DESIGN, SETTING, AND PATIENTS: Open-label study of 22 patients diagnosed as having probable SARS at North York General Hospital, Toronto, Ontario, between April 11 and May 30, 2003. INTERVENTIONS: Thirteen patients were treated with corticosteroids alone and 9 patients were treated with corticosteroids plus subcutaneous interferon alfacon-1. MAIN OUTCOME MEASURES: Clinical parameters, including oxygen saturation and requirement, laboratory measures, and serial chest radiography results. RESULTS: Resolution of fever and lymphopenia were similar between the 2 treatment groups. Of the 13 patients treated with corticosteroids alone, 5 (38.5%) were transferred to the intensive care unit, 3 (23.1%) required intubation and mechanical ventilation, and 1 (7.7%) died. Of the 9 patients in the interferon alfacon-1 treatment group, 3 (33.3%) were transferred to the intensive care unit, 1 (11.1%) required intubation and mechanical ventilation, and none died. The interferon alfacon-1 treatment group had a shorter time to 50% resolution of lung radiographic abnormalities (median time, 4 days vs 9 days; P =.001), had better oxygen saturation (P =.02), resolved their need for supplemental oxygen more rapidly (median, 10 days vs 16 days; P =.02), had less of an increase in creatine kinase levels (P =.03), and showed a trend toward more rapid resolution of lactate dehydrogenase levels compared with the group receiving corticosteroids alone. CONCLUSIONS: In this preliminary, uncontrolled study of patients with SARS, use of interferon alfacon-1 plus corticosteroids was associated with reduced disease-associated impaired oxygen saturation, more rapid resolution of radiographic lung abnormalities, and lower levels of creatine kinase. These findings suggest that further investigation may be warranted to determine the role of interferon alfacon-1 as a therapeutic agent for the treatment of SARS.

Adult↗
PubMed2003

Effect of HIV-1 antiretroviral drugs on cytoadherence and phagocytic clearance of Plasmodium falciparum-parasitised erythrocytes.

In response to the HIV/AIDS pandemic, antiretroviral treatment is currently being implemented in sub-Saharan Africa, where malaria and HIV-1 co-infections are highly prevalent. The effectiveness and tolerability of antiretrovirals in patients with malaria and HIV-1 co-infection have not been investigated. Antiretrovirals decrease CD36 surface concentrations in vivo, which might impair receptor function and affect parasite-host interactions. Thus, we investigated the effects of these drugs on CD36-mediated cytoadherence and non-opsonic phagocytosis of Plasmodium falciparum parasitised erythrocytes in vitro. The protease-inhibitor class of antiretrovirals particularly impairs CD36-mediated cytoadherence and non-opsonic phagocytosis of parasitised erythrocytes by human macrophages. Such treatment might therefore contribute to altered malaria disease outcomes in co-infected patients.

Africa South of the Sahara↗
PubMed2003

Genetic confirmation of atovaquone-proguanil-resistant Plasmodium falciparum malaria acquired by a nonimmune traveler to East Africa.

We report a case of atovaquone-proguanil-resistant Plasmodium falciparum malaria acquired by a nonimmune traveler to Kenya. Recurrent parasitemia occurred 30 days after directly observed therapy with a combination of atovaquone and proguanil. Treatment failure was confirmed by genetic fingerprinting and sequencing. The primary isolate had wild-type sequence of cytochrome b; however, the recrudescent isolate had a single mutation at position 268 (Tyr268Ser).

Adult↗