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Articles by Stephen A. Klotz in JoVE
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HIV에 감염된 개인의 연약함을 측정합니다. 허약 환자의 식별 개량과 연약함 환입하는 첫 번째 단계입니다
Hilary C. Rees1, Voichita Ianas1, Patricia McCracken1, Shannon Smith1, Anca Georgescu1, Tirdad Zangeneh1, Jane Mohler2, Stephen A. Klotz1
1Division of Infectious Diseases, University of Arizona, 2Arizona Center on Aging, University of Arizona
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HIV와 함께 사는 나이 많은 사람에 Exergaming 것은 균형, 이동성을 개선하고 약함의 일부 측면을 개선한다
Suhitha Veeravelli1, Bijan Najafi3, Ivan Marin3, Fernando Blumenkron2, Shannon Smith2, Stephen A. Klotz2
1Department of Surgery, Interdisciplinary Consortium on Advanced Motion Performance (iCAMP), College of Medicine, University of Arizona, 2Department of Medicine, Division of Infectious Disease, College of Medicine, University of Arizona, 3Interdisciplinary Consortium on Advanced Motion Performance (iCAMP), Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine
HIV에 감염된 사람은 종종 우울, 허약하고 기존의 운동이 너무 과세되는 앉아있는 라이프 스타일을 살고있다. 여기, 우리는 HIV에 감염된 사람의 연약함의 측면을 개선한다 운동 프로토콜을 제시한다. 인지 제어를 통합합니다 exergame는 균형, 체중 이동과 장애물 횡단을 측정 바이오 센서를 사용하여 개발되었다.
Other articles by Stephen A. Klotz on PubMed
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Candida Albicans and Saccharomyces Cerevisiae Expressing ALA1/ALS5 Adhere to Accessible Threonine, Serine, or Alanine Patches
Cell Communication & Adhesion.
Jan-Feb, 2002 |
Pubmed ID: 12200964 Saccharomyces cerevisiae transformed with Candida albicans ALA1/ALS5 exhibits adherence properties similar to C. albicans. Adherence of the fungi to immobilized proteins involves hydrogen bonds, is stable to shear forces, and is resistant to competition from various biological molecules. The specificity determinants of target recognition in Ala1/Als5p-mediated adherence are not known. To determine features of target recognition, proteins and small peptides were covalently coupled at the N-terminus to the surface of carboxylate-modified magnetic beads. C. albicans yeast cells, germ tubes and pseudohyphae and S. cerevisiae expressing the adhesin, Ala1/Als5p, adhered to beads coated with fibronectin, laminin, type IV collagen, bovine serum albumin, and casein. No adherence to beads was observed if a single amino acid was coupled to the beads. However, 10-mer homopolymers of threonine, serine, and alanine served as ligands for adherence. The presence of a minimum of four contiguous threonine residues in a peptide was required for maximal adherence. Coupling of 10-mer peptides from fibronectin and Ala1/Als5p each possessing 5-7 threonine or serine residues also initiated adherence. On the other hand, a collagen and a fibronectin 10-mer peptide with few threonine and serine residues and lysine at the C-terminus did not serve as adherence ligands. Both of them are converted to adherence ligands by adding threonine or serine residues at the C-terminus or removing the lysine residue and adding threonine residues anywhere in the peptide. The presence of lysine at the C-terminus may have resulted in coupling of the peptides at both the N- and C-termini, thus making the threonine residues inaccessible for adherence. Thus, Ala1/Als5p recognizes patches of certain amino acids, which must be accessible before adherence will occur.
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Accessibility of the Peptide Backbone of Protein Ligands is a Key Specificity Determinant in Candida Albicans SRS Adherence
Microbiology (Reading, England).
Feb, 2004 |
Pubmed ID: 14766905 Candida albicans displays a high degree of specificity in selecting and adhering to targets in vivo. The features of target recognition are poorly understood and likely to involve more than the mere chemical composition of the ligand. Using an adherence assay in which protein and peptide ligands are covalently coupled to magnetic beads, the authors have previously described a new adherence mechanism in C. albicans, henceforth referred to as SRS (stable, reversible, specific) adherence. It was previously demonstrated that C. albicans and Saccharomyces cerevisiae expressing agglutinin-like sequence 5 protein (Als5p, previously referred to as Ala1p or Ala1/Als5p) adhere to peptides containing patches of threonine, serine and alanine residues when these are located in the free end of immobilized peptides. The interaction with protein ligands in SRS adherence predominantly involves the formation of hydrogen bonds. Accordingly, this interaction may occur (1) to the peptide backbone of the protein ligand or (2) to the amino acid side chain with an appropriate functional group. Evidence is provided that the primary interaction occurs with the peptide backbone and the secondary interaction occurs with the side chain. The primary interaction with the peptide backbone is sufficient for adherence to occur, whereas the secondary interaction with a side chain possessing an appropriate functional group stabilizes the interaction. In agreement with these results, it is also demonstrated that proteins lacking secondary and tertiary structure, wherein the peptide backbone is sterically accessible, interact with C. albicans and S. cerevisiae expressing Als5p. C. albicans Als proteins are resistant to denaturation by harsh conditions that kill the yeast cells. The proposed interactions in SRS adherence have striking similarities with those of the molecular chaperone Hsp70, which specifically binds to non-native proteins and resists denaturation.
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Inhibition of Adherence and Killing of Candida Albicans with a 23-Mer Peptide (Fn/23) with Dual Antifungal Properties
Antimicrobial Agents and Chemotherapy.
Nov, 2004 |
Pubmed ID: 15504862 Candida albicans adheres to host tissue and then proliferates in order to establish a commensal as well as a pathogenic state. Specific adherence to proteins is provided by several surface adhesins of Candida. Two well-studied proteins, Als1p and Als5p, do not require energy for adherence to occur (dead as well as living cells adhere) and have a multiplier effect of cell-cell aggregation that mediates the formation of microcolonies of Candida cells. The entire process is spontaneous, reversible, and stable for physiologically relevant chemical and physical forces. This adherence process is inhibited by the addition of free peptide ligands, including a 23-mer derived from fibronectin (Fn/23) that binds to the adhesins through H bond formation. Adherence was measured by determining the number of yeast cells that adhered to 90-microm-diameter polyethylene glycol (PEG) beads with a 7-mer peptide (KLRIPSV) synthesized on the surfaces of the beads. The concentration of the Fn/23 peptide that inhibited the adherence of cells to the peptide-coated beads by 50% was 4 to 5 microM, and the magnitudes of adherence were similar regardless of the presence or absence of physiologic salt concentrations. The minimum fungicidal concentration of Fn/23 was 2 to 4 microM in water, but there was no killing in physiologic salt concentrations. Peptides from the C and N termini or the center sequence of Fn/23 had no effect on inhibition of adherence and little effect on fungal viability. The fungicidal effect was similar to that seen with 23-, 19-, and 18-mer peptides derived from porcine myeloid cells, a Helicobacter pylori ribosomal protein, and a hybrid of cecropin and magainin, respectively. However, these fungicidal peptides did not inhibit C. albicans adherence to the peptide-coated PEG beads. This dual property of Fn/23, i.e., inhibition of adherence and killing of C. albicans, may provide important adjuvant effects in the treatment of disease caused by this fungus.
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Threonine-rich Repeats Increase Fibronectin Binding in the Candida Albicans Adhesin Als5p
Eukaryotic Cell.
Oct, 2006 |
Pubmed ID: 16936142 Commensal and pathogenic states of Candida albicans depend on cell surface-expressed adhesins, including those of the Als family. Mature Als proteins consist of a 300-residue N-terminal region predicted to have an immunoglobulin (Ig)-like fold, a 104-residue conserved Thr-rich region (T), a central domain of a variable number of tandem repeats (TR) of a 36-residue Thr-rich sequence, and a heavily glycosylated C-terminal Ser/Thr-rich stalk region, also of variable length (N. K. Gaur and S. A. Klotz, Infect. Immun. 65: 5289-5294, 1997). Domain deletions in ALS5 were expressed in Saccharomyces cerevisiae to excrete soluble protein and for surface display. Far UV circular dichroism indicated that soluble Ig-T showed a single negative peak at 212 nm, consistent with previous data indicating that this region has high beta-sheet content with very little alpha-helix. A truncation of Als5p with six tandem repeats (Ig-T-TR(6)) gave spectra with additional negative ellipticity at 200 nm and, at 227 to 240 nm, spectra characteristic of a structure with a similar fraction of beta-sheet but with additional structural elements as well. Soluble Als5p Ig-T and Ig-T-TR(6) fragments bound to fibronectin in vitro, but the inclusion of the TR region substantially increased affinity. Cellular adhesion assays with S. cerevisiae showed that the Ig-T domain mediated adherence to fibronectin and that TR repeats greatly increased cell-to-cell aggregation. Thus, the TR region of Als5p modulated the structure of the Ig-T region, augmented cell adhesion activity through increased binding to mammalian ligands, and simultaneously promoted fungal cell-cell interactions.
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Candida Albicans Als Proteins Mediate Aggregation with Bacteria and Yeasts
Medical Mycology : Official Publication of the International Society for Human and Animal Mycology.
Jun, 2007 |
Pubmed ID: 17510860 Candida albicans occupies a microniche on mucosal surfaces where diverse microbial populations interact within a biofilm. Because C. albicans is intimately involved with other microbes in this environment we studied the interactions of C. albicans with other fungi and bacteria that form mixed microbial aggregates. Once aggregation is initiated, aggregates form rapidly and incorporate fungal as well as bacterial cells. The fungus formed mixed microbial aggregates with homotypic cells (i.e., self to self, e.g., C. albicans or Als1p-expressing yeast cells aggregating with cells bearing Als1p); with heterotypic cells (i.e., self to non-self, e.g., C. albicans or Alsp-expressing yeast cells aggregating with other Candida species); and with xenotypic cells (e.g., C. albicans or Alsp-expressing yeast cells forming aggregates with bacteria). When either of the C. albicans adhesins Als1p or Als5p was displayed on the surface of non-adherent Saccharomyces cerevisiae cells, the S. cerevisiae also mediated these mixed microbial interactions. Thus the Als adhesins are potentially important for the co-adhesion of mixed microbial communities in biofilms and on mucus surfaces.
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Clinical Features of HIV/AIDS Patients Presenting to an Inner City Clinic in Ho Chi Minh City, Vietnam
International Journal of STD & AIDS.
Jul, 2007 |
Pubmed ID: 17623507 An outpatient HIV clinic was opened in March 2005 in Binh Thanh District, a poor section of Ho Chi Minh City, Vietnam. Over 1500 patients were seen in the first year. The average age of patients was 27 years. Men represented 77% of the clinic population, women, 23% and children under the age of 16 years of age, 5% of the population. The most common risk factor among men was being an injecting drug user (IDU), 76%, and among women, being married to an IDU HIV-positive man, 35%. Physical signs of disease were uncommon: lymphadenopathy in 24% and hepatomegaly and splenomegaly in 4% and 3%, respectively. Men and women were anaemic at presentation, with a mean haemoglobin of 11.9 g/dL and 11.1 g/dL, respectively. An overwhelming majority of patients had profound immunodeficiency. The mean CD4+ cell count was 164 cells/mL and the median was 69 cells/mL. No correlation was found between the World Health Organization's stage of disease and the CD4+ cell count. Thus, the former is a poor predictor of immunity in this population. Data regarding opportunistic infections diagnosed at the first visit were studied. Candidiasis of the oral pharynx, oesophagus or vagina was found in 34.5% of the patients, and pulmonary and extrapulmonary tuberculosis was found in 32% of the patients. Pneumocystis carinii pneumonia (PCP) was diagnosed in only 3% of the patients. Cotrimoxazole prophylaxis is advocated for HIV-infected Vietnamese, but the incidence of PCP is negligible and resources could be spent elsewhere. The various opportunistic infections seen in this resource-poor clinic setting is likely to be a pattern of presentation of HIV-infected Vietnamese for some time to come.
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Polymicrobial Bloodstream Infections Involving Candida Species: Analysis of Patients and Review of the Literature
Diagnostic Microbiology and Infectious Disease.
Dec, 2007 |
Pubmed ID: 17888612 Candida species are the 4th most common cause of nosocomial bloodstream infections in North America. It is not widely appreciated, however, that many of these infections are polymicrobial, that is, that bacteria and occasionally more than 1 species of Candida are present in the same blood culture bottle. Analysis of 2 groups of candidemic patients and a review of the literature were performed. Review of 141 candidemic patients from 8 Veterans Affairs hospitals and 231 patients from a tertiary care hospital with transplant services was performed. Of the 372 patients with candidemia, 100 (27%) had polymicrobial blood cultures: 88 patients (24%) had synchronous bacteremia and 12 patients (3%) had more than 1 species of Candida. One hundred bacteria were isolated from these patients, 69 were Gram positive, and 31 were Gram negative. Candidemia was shown to occur in a setting of polymicrobial bacteremia extending over days, whereas Staphylococcus aureus and coagulase-negative Staphylococcus were less frequently associated with polymicrobial bloodstream infections. Review of more than 8000 reported episodes of candidemia revealed high rates of polymicrobial infection occurring with candidemia. Of blood cultures isolating Candida, 23% were polymicrobial and 4% had more than 1 species of Candida. Thus, almost 1 in 4 patients with candidemia will have a polymicrobial bloodstream infection. As detection of bloodborne infections evolves toward nonculture methodologies, documentation of the frequency of polymicrobial bloodstream infections involving Candida is important. This finding may have treatment implications for clinicians.
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The Older HIV-positive Adult: a Critical Review of the Medical Literature
The American Journal of Medicine.
Dec, 2008 |
Pubmed ID: 19028193 Older adults make up an ever-growing proportion of human immunodeficiency virus (HIV) cases in the United States, with approximately 25% of infections occurring in adults over the age of 50 years. Although there is a preliminary body of literature addressing the socioeconomic and prognostic issues of HIV infection in older adults, very little rigorous scientific research has looked at the significant clinical issues relevant to this growing population. Treatment of older adults is complicated by an increased prevalence of medical comorbidities, but little is known about the effects of complicated medication regimens in this group, as they are routinely excluded from clinical trials of newer HIV medications. The delay in diagnosis and treatment of HIV in older adults has led to poorer outcomes, including lower baseline CD4 counts, decreased time to acquired immune deficiency syndrome diagnosis, and increased mortality. Despite these facts, there is mounting evidence that timely diagnosis and treatment of HIV in older adults leads to improved outcomes, similar to younger patients. This review evaluates the literature focusing on HIV and older adults.
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Animal Bites and Stings with Anaphylactic Potential
The Journal of Emergency Medicine.
Feb, 2009 |
Pubmed ID: 17997071 Anaphylaxis to animal bites and stings poses a significant medical risk of vascular or respiratory reactions that vary according to the patient's response and nature of the insult. Emergency Physicians frequently see patients who complain of an allergic reaction to an animal bite or sting. Although Hymenoptera stings, specifically those of wasps, bees, and hornets, account for the majority of these cases, other invertebrates and vertebrates are capable of causing allergic reactions and anaphylaxis. Many of the causative animals are quite unusual, and their bites and stings are not commonly appreciated as potential causes of anaphylaxis. We conducted a literature review to identify documented reports of anaphylaxis and anaphylactoid reactions to animal bites and stings. This summary is meant to heighten awareness of the diversity of animals that may cause anaphylaxis, hopefully leading to more rapid diagnosis and treatment of this dangerous condition. A diverse group of animals was found whose bites and stings cause anaphylaxis and anaphylactoid reactions. Some case summaries are presented. A potentially life-saving plan is to direct patients to proper follow-up care to prevent a future life-threatening reaction, including: prescribing epinephrine and antihistamines with proper instructions for their use; referral to an allergist to determine if skin testing, radioallergosorbent test, and immunotherapy are indicated; and reporting the case to state or local Poison Control Centers. In some cases it may be helpful to consult an entomologist or a pest control service for help in identification and elimination of certain offenders.
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Immune Reconstitution Inflammatory Syndrome in a Resource-poor Setting
Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. : 2002).
Mar-Apr, 2009 |
Pubmed ID: 19258527 The immune reconstitution inflammatory syndrome (IRIS) associated with highly active antiretroviral therapy (HAART) was studied in rural Ethiopian HIV-infected patients. Review of 1002 charts in an outpatient clinic was conducted. The median CD4 count was 89 cells/mm(3). Ninety-eight patients were hospitalized after initiation of HAART, of whom 74 were hospitalized for manifestations of IRIS (ie, 7% of patients on HAART). Of the 74 patients hospitalized with IRIS, 27 patients had tuberculosis; 12 patients, cryptococcal meningitis; 7 patients, toxoplasmosis; 6 patients, pneumonia and/or effusion; and 5 patients, Pneumocystis jiroveci pneumonia (PCP). Ten adult patients were admitted with gastroenteritis, heretofore not recognized as a manifestation of IRIS. Eighty-one percent of IRIS patients were hospitalized within 3 months of beginning HAART and 99% by 6 months. Of those hospitalized with IRIS, 4 patients (5%) died while in the hospital (3 with cryptococcal meningitis). Thirty-seven or 50% of those hospitalized with IRIS were lost to medical follow up, thus the mortality rate is likely a gross underestimate of the severity of IRIS. In resource-poor settings where the primary goal is to initiate HAART, IRIS may go unrecognized and have fatal consequences.
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Feeding Behavior of Triatomines from the Southwestern United States: an Update on Potential Risk for Transmission of Chagas Disease
Acta Tropica.
Aug, 2009 |
Pubmed ID: 19524078 Chagas disease is an emerging infectious disease in North America due to the immigration of individuals from endemic areas. The parasite has been transmitted to patients in non-endemic areas by blood transfusion and organ donation. Only six autochthonous cases have been described in humans in the United States yet the parasite is widespread among native mammals and resident triatomines are competent vectors. We attempted to determine if common southwestern triatomines, Triatoma protracta and Triatoma rubida have the potential to amplify the disease among human residents of the Southwest. The defecation patterns of the bugs were studied while feeding upon immobilized mice. Wild-caught adult male and female triatomines were observed feeding one to three times for a total of 71 observed feedings. T. rubida (15 bugs) appeared to be more aggressive, beginning feeding shortly after being placed in proximity to the host (within 2.3 min) whereas Triatoma protracta (12 bugs) was more deliberate, beginning feeding, on average, at 4 min. There were 40 observations of T. rubida, which fed for 27.9+/-13.6 min, whereas T. protracta fed for 22.8+/-7.5 min (n=31). Bugs were weighed pre- and post-feeding and T. rubida females ingested>T. protracta females>T. rubida males>T. protracta males. Weight gain did not correspond to the feeding duration. Defecation occurred on 42% of the feedings (30 of 71), and no bugs defecated on the host. The majority of the defecations occurred within 1 min of feeding, usually at the time of repletion. A large proportion of defecations occurred after the bugs left the vicinity of the host. All bugs and at least one fecal smear from each feeding bug were tested for Trypanosoma cruzi and 21% of T. protracta were positive by PCR (4 bugs and 1 feces). No T. rubida tested positive for T. cruzi. The bugs' defecation pattern is similar to that reported >50 years ago. Furthermore, there is no indication that they are becoming more domesticated in the desert Southwest. Thus, based on our observations, we do not believe that T. protracta and T. rubida pose an imminent risk for transmission of Chagas disease to residents of the southwestern United States.
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Structure and Function of Glycosylated Tandem Repeats from Candida Albicans Als Adhesins
Eukaryotic Cell.
Mar, 2010 |
Pubmed ID: 19820118 Tandem repeat (TR) regions are common in yeast adhesins, but their structures are unknown, and their activities are poorly understood. TR regions in Candida albicans Als proteins are conserved glycosylated 36-residue sequences with cell-cell aggregation activity (J. M. Rauceo, R. De Armond, H. Otoo, P. C. Kahn, S. A. Klotz, N. K. Gaur, and P. N. Lipke, Eukaryot. Cell 5:1664-1673, 2006). Ab initio modeling with either Rosetta or LINUS generated consistent structures of three-stranded antiparallel beta-sheet domains, whereas randomly shuffled sequences with the same composition generated various structures with consistently higher energies. O- and N-glycosylation patterns showed that each TR domain had exposed hydrophobic surfaces surrounded by glycosylation sites. These structures are consistent with domain dimensions and stability measurements by atomic force microscopy (D. Alsteen, V. Dupres, S. A. Klotz, N. K. Gaur, P. N. Lipke, and Y. F. Dufrene, ACS Nano 3:1677-1682, 2009) and with circular dichroism determination of secondary structure and thermal stability. Functional assays showed that the hydrophobic surfaces of TR domains supported binding to polystyrene surfaces and other TR domains, leading to nonsaturable homophilic binding. The domain structures are like "classic" subunit interaction surfaces and can explain previously observed patterns of promiscuous interactions between TR domains in any Als proteins or between TR domains and surfaces of other proteins. Together, the modeling techniques and the supporting data lead to an approach that relates structure and function in many kinds of repeat domains in fungal adhesins.
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Yeast Cell Adhesion Molecules Have Functional Amyloid-forming Sequences
Eukaryotic Cell.
Mar, 2010 |
Pubmed ID: 20038605 The occurrence of highly conserved amyloid-forming sequences in Candida albicans Als proteins (H. N. Otoo et al., Eukaryot. Cell 7:776-782, 2008) led us to search for similar sequences in other adhesins from C. albicans and Saccharomyces cerevisiae. The beta-aggregation predictor TANGO found highly beta-aggregation-prone sequences in almost all yeast adhesins. These sequences had an unusual amino acid composition: 77% of their residues were beta-branched aliphatic amino acids Ile, Thr, and Val, which is more than 4-fold greater than their prevalence in the S. cerevisiae proteome. High beta-aggregation potential peptides from S. cerevisiae Flo1p and C. albicans Eap1p rapidly formed insoluble amyloids, as determined by Congo red absorbance, thioflavin T fluorescence, and fiber morphology. As examples of the amyloid-forming ability of the native proteins, soluble glycosylphosphatidylinositol (GPI)-less fragments of C. albicans Als5p and S. cerevisiae Muc1p also formed amyloids within a few days under native conditions at nM concentrations. There was also evidence of amyloid formation in vivo: the surfaces of cells expressing wall-bound Als1p, Als5p, Muc1p, or Flo1p were birefringent and bound the fluorescent amyloid-reporting dye thioflavin T. Both of these properties increased upon aggregation of the cells. In addition, amyloid binding dyes strongly inhibited aggregation and flocculation. The results imply that amyloid formation is an intrinsic property of yeast cell adhesion proteins from many gene families and that amyloid formation is an important component of cellular aggregation mediated by these proteins.
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Cat-scratch Disease
American Family Physician.
Jan, 2011 |
Pubmed ID: 21243990 Cat-scratch disease is a common infection that usually presents as tender lymphadenopathy. It should be included in the differential diagnosis of fever of unknown origin and any lymphadenopathy syndrome. Asymptomatic, bacteremic cats with Bartonella henselae in their saliva serve as vectors by biting and clawing the skin. Cat fleas are responsible for horizontal transmission of the disease from cat to cat, and on occasion, arthropod vectors (fleas or ticks) may transmit the disease to humans. Cat-scratch disease is commonly diagnosed in children, but adults can present with it as well. The causative microorganism, B. henselae, is difficult to culture. Diagnosis is most often arrived at by obtaining a history of exposure to cats and a serologic test with high titers (greater than 1:256) of immunoglobulin G antibody to B. henselae. Most cases of cat-scratch disease are self-limited and do not require antibiotic treatment. If an antibiotic is chosen, azithromycin has been shown in one small study to speed recovery. Infrequently, cat-scratch disease may present in a more disseminated form with hepatosplenomegaly or meningoencephalitis, or with bacillary angiomatosis in patients with AIDS.
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The Immune Reconstitution Inflammatory Syndrome with Tuberculosis: A Common Problem in Ethiopian HIV-Infected Patients Beginning Antiretroviral Therapy
Journal of the International Association of Physicians in AIDS Care (Chicago, Ill. : 2002).
May-Jun, 2012 |
Pubmed ID: 21521804 The Immune Reconstitution Inflammatory Syndrome (IRIS) in Ethiopian HIV-infected patients coinfected with tuberculosis (TB) was studied. HIV-infected outpatients initiating antiretroviral therapy (ART) at an HIV clinic in northern Ethiopia from January 2007 through September 2008 were identified (n = 1977). Patients with TB-IRIS occurring within 6 months of starting ART (n = 143) were compared with a control group of patients with HIV who began ART but did not develop TB-IRIS (n = 277). ART was not interrupted in any patient. Eleven (8%) patients with TB-IRIS died. New or "unmasked" TB with accompanying IRIS occurred in 132 or 92% of the cases. Worsening or "paradoxical" TB (ie, already known to be present and treated) was accompanied by IRIS in 11 (8%) patients. There was no significant difference between "unmasked" and "paradoxical" cases with respect to presentation of disease and outcome. Only a low baseline CD4 count (mean: 102 cells/μL) and a past history of World Health Organization (WHO) Clinical Stage 3 or 4 were associated with TB-IRIS (P < .05). The clinical manifestations of TB-IRIS were diverse, requiring a high index of suspicion. For example, pleural disease occurred in 13 patients, TB lymphadenitis in 17, intracranial TB in 9 patients, and disseminated TB in 15 patients. The majority of patients (88%) responded to continuation of ART and TB therapy. Thus, TB-IRIS is common in Ethiopian patients beginning ART, occurring in 7% of patients initiating antiretroviral therapy.
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Antiretroviral Therapy Protects Against Frailty in HIV-1 Infection
Journal of the International Association of Providers of AIDS Care.
Feb, 2013 |
Pubmed ID: 23042791 HIV-1-infected patients are surviving longer and by 2015 half will be older than 50 years of age. Frailty is a syndrome associated with advanced age but occurs in HIV-1-infected patients at younger ages. One hundred outpatient HIV-1-infected persons were prospectively tested for clinical markers of frailty: shrinking weight, slowness in walking, decrease in grip strength, low activity, and exhaustion. Age, length of infection with HIV, CD4 count, HIV-1 RNA, and comorbidities were compared. CD4 counts 350 cells/mm(3) (odds ratio [OR] 9.0, 95% confidence interval [CI] 2.1-44). Seven frail patients were measured 6 months later: 2 died refusing therapy, 4 were no longer frail, and 1 patient remained frail. We conclude that frailty is common in HIV outpatients and is associated with low CD4 counts. However, our data suggest that frailty is transient, especially in younger patients who may revert to their prefrail state unlike uninfected elderly individuals in whom a stepwise decline in function occurs.
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Kissing Bugs in the United States: Risk for Vector-borne Disease in Humans
Environmental Health Insights.
2014 |
Pubmed ID: 25574143 Eleven species of kissing bugs are found in the United States. Their home ranges may be expanding northward, perhaps as a consequence of climate change. At least eight of the species, perhaps all, are reported to harbor Trypanosoma cruzi, the parasite that causes Chagas disease. Because humans are encroaching on kissing bug habitat, there is concern for vector-transmitted Chagas disease in the United States. To date, documented autochthonous cases of Chagas in humans in the United States are rare. Kissing bugs are capable of adapting to new habitats such as human domiciles; however, they do not colonize homes in the United States as in Central and South America. We review the biology, behavior, and medical importance of kissing bugs and the risk they pose for transmission of Chagas disease in the United States. Where possible, descriptions of US species are compared to the epidemiologically important Latin American species.
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Positive (1-3) B-d-glucan and Cross Reactivity of Fungal Assays in Coccidioidomycosis
Medical Mycology.
Feb, 2015 |
Pubmed ID: 25541557 Fungal antigen testing in immunosuppressed patients has emerged as a powerful diagnostic tool. Some assays are relatively nonspecific, and misinterpretation can have severe clinical consequences. Additionally, when new assays become commercially available it is important to evaluate the potential for cross reactivity. We recently observed several immunosuppressed patients with positive (1→3)-β-D-glucan (BG) who were eventually diagnosed with coccidioidomycosis in the endemic area of Tucson, Arizona. Although the BG assay is known to detect glucans of many fungal pathogens, reports of cross-reactivity with Coccidioides remain sparsely reported. To test the cross-reactivity of fungal antigens in detection assays, serum samples from patients with coccidioidomycosis testing positive for Coccidioides antigen were evaluated for BG. Of 12 samples positive for Coccidioides antigen (≥0.07 ng/ml), 11 (92%) were positive by BG (>80 pg/ml), and of 11 positive for Aspergillus galactomannan, 10 (91%) were positive by BG (>80 pg/ml). We conclude that the BG assay is nonspecific, detecting glucans from many fungal pathogens, including Coccidioides. In the endemic area, a positive BG warrants further specific testing.
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Kissing Bug (Triatoma Spp.) Intrusion into Homes: Troublesome Bites and Domiciliation
Environmental Health Insights.
2016 |
Pubmed ID: 27042091 Kissing bugs (Triatoma spp.) frequently enter homes and bite human and pet occupants. Bites may lead to severe allergic reactions and, in some cases, death. Kissing bugs are also vectors of Trypanosoma cruzi, the cause of Chagas disease. In general, modern houses in the United States are not conducive to domiciliation of kissing bugs (bugs living out their entire life within the home with the presence of eggs, nymphs, adults, and exuviae). Construction features such as concrete foundations, solid walls and ceilings, window screens, tight thresholds for doors and windows, and other measures impede bug entry into homes, and air conditioning reduces the need for open doors and windows. Where Chagas disease is endemic in Mexico and Central and South America, homes often have thatch roofs, adobe walls, and open doors and windows. We investigated numerous instances of kissing bug intrusions into homes in Southern Arizona, California, and Louisiana and documented the reactions to kissing bug bites. Our work confirms the importance of modern home construction in limiting kissing bug intrusions. Older homes, especially those lacking modern screening, caulking, and weather stripping to reduce air leakage, may be subject to kissing bug intrusions and domiciliation. We describe a community in Southern Arizona where domiciliation of homes by Triatoma recurva is common. We also provide recent data regarding kissing bug bites and allergic reactions to the bites.
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