Effects of Chin-Down Maneuver on Pharyngeal Pressure Generation According to Dysphagia and Viscosity.

OBJECTIVE: To demonstrate the effects of chin-down maneuver on swallowing by using high-resolution manometry (HRM). METHODS: HRM data of 20 healthy subjects and 64 dysphagic patients were analyzed. Participants swallowed 5 mL of thin and honey-like liquids in neutral and chin-down positions. HRM was used to evaluate maximal velopharyngeal pressure/area, maximal tongue base pressure/area, maximal pharyngeal constrictor pressure, pre-/post-swallow upper esophageal sphincter (UES) peak pressure, minimal UES pressure, UES activity time, and nadir duration. RESULTS: Compared to the neutral position, the chin-down maneuver significantly increased tongue base pressure in both normal and dysphagic groups as well as for both honey-like and thin viscosities, although the honey-like liquid did not reach statistical significance in the dysphagic group. Regarding pharyngeal constrictors and pre-swallow peak UES pressure, the healthy group showed a significant decrease in thin liquid swallowing and decreasing tendency in honeylike liquid swallowing. UES nadir duration was significantly decreased for honey-like liquid swallowing in the dysphagic group and for both thin and honey-like liquids in the healthy group. UES nadir duration of honey-like and thin flow swallowing in the dysphagia group was 0.26 seconds after the chin-down maneuver, which was severely limited. CONCLUSION: This study showed a different kinetic effect of the chin-down maneuver between the healthy and dysphagic groups, as well as between thin and honey-like viscosities. The chin-down maneuver increased tongue base pressure and decreased UES nadir duration, which the latter was severely limited in dysphagic patients. Therefore, appropriate application of the chin-down maneuver in clinical practice is required.

Application of Automatic Kinematic Analysis Program for the Evaluation of Dysphagia in ALS patients.

Dysphagia in amyotrophic lateral sclerosis (ALS) increases the risk of malnutrition, dehydration, and aspiration pneumonia. Kinematic analysis of videofluoroscopic swallowing study (VFSS) can provide detailed movement of the hyoid bone, revealing abnormalities of swallowing in ALS patients. We developed an automated kinematic analysis program (AKAP) that analyzes the trajectory of the hyoid bone via a visual tracking method. The aim of this study was to investigate the hyoid movement in ALS patients using AKAP and compare it with non-dysphagic subjects. Thirty ALS patients who underwent VFSS in Seoul National University Bundang Hospital between 2015 and 2017 were recruited. For comparison, 30 age-matched control subjects were also enrolled; the same swallowing study was conducted using thin fluid and yogurt. The hyoid bone movement was analyzed by evaluating the vertical and horizontal distances with four peak points (A, B, C, D), and the time of each point were also calculated. With respect to distance parameters, only vertical peak distance (distance between B, D points) during thin fluid swallowing was significantly decreased in ALS patients. (p = 0.038) With respect to temporal parameters, Time ABC, Time ABCD, and Duration C were significantly increased in ALS patients when swallowing both thin fluid and yogurt. (Time ABC p = 0.019, p = 0.002; Time ABCD p = 0.001, p = 0.004; Duration C p = 0.004, p = 0.025 respectively). This result revealed that dysphagia in ALS patient is caused by decreased velocity of hyoid bone movement due to the development of weakness in swallowing-related muscles. The parameters of kinematic analysis could be used to quantitatively evaluate dysphagia in motor neuron disease.

Characterization of Clinical Isolates of Bartonella henselae Strains, South Korea.

Bartonella henselae, a gram-negative bacterium, is a common causative agent of zoonotic infections. We report 5 culture-proven cases of B. henselae infection in South Korea. By alignment of the 16S rRNA sequences and multilocus sequencing typing analysis, we identified all isolates as B. henselae Houston-1 strain, which belongs to sequence type 1.

Serologic Study of Bartonella henselae in Patients with Acute Undifferentiated Febrile Illness in Korea.

BACKGROUND: Bartonella infection is an emerging cause of acute febrile illness; however, its significance has not been thoroughly investigated. We studied the antibody specific to Bartonella henselae in patients with various febrile diseases in Korea. MATERIALS AND METHODS: A total of 177 patients with acute febrile illness who were managed at the Inha University Hospital from February 2012 to January 2013 were evaluated with an in-house immunofluorescent antibody test to detect B. henselae immunoglobulin G (IgG) antibody. The clinical features of the patients included fever of undetermined origin (n = 88 patients), lymphadenopathy (n = 28), febrile rash (n = 17), respiratory infection (n = 12), aseptic meningitis (n = 7), intra-abdominal infection (n = 5), arthritis (n = 4), and other conditions (n = 16). We reviewed the medical records of these patients and collected demographic data, clinical features, and their histories of animal exposure. RESULTS: Among the 177 patients with acute febrile illness, 23.7% (42/177) had elevated levels of IgG antibodies to B. henselae (≥1:160). Of these seropositive patients, 32.4% (12/37) had contact with animals and had developed arthralgia (29.5%), headache (25%), or lymphadenopathy (15.9%). Seven (16.7%) of the 42 patients had higher IgG titers (≥1:640). Among them, four patients presented fourfold increase/decrease of IgG in convalescent serum. According to the clinical diagnosis, the antibody positivity rates were as follows: 24/88 with undifferentiated fever, 8/28 with lymphadenopathy, 4/17 with febrile rash, 2/12 with respiratory infection, 2/7 with aseptic meningitis, and 2/16 with other illnesses. CONCLUSIONS: There was high prevalence of B. henselae in patients with undifferentiated fever in Korea, for which further research is needed.

The seroprevalence of Bartonella henselae in healthy adults in Korea.

BACKGROUND/AIMS: Cat-scratch disease (CSD), caused by Bartonella henselae is one of the most common zoonosis. However, only several cases of B. henselae infection have been reported in Korea. This study investigated the seroprevalence of B. henselae in healthy adults and related risk factors. METHODS: Serum samples from 300 healthy participants were analyzed using an immunoglobulin G immunof luorescence assay (IFA) for B. henselae isolated in Korea. Surveys on the risk factors for B. henselae infection were conducted simultaneously. RESULTS: Of the participants, 47.7% and 15.0% raised dogs and cats, respectively. The overall seroprevalence of B. henselae was 15.0% (IFA titer ≥ 1:64). Participants who had raised cats showed 22.2% seropositivity against B. henselae, and those with no experience with cats showed 13.7% seroprevalence (p = 0.17). Participants who had cats as pets or been scratched by cats, showed 9.8% seropositivity against B. henselae (IFA titer ≥ 1:256). However, those who had not raised or been scratched by a cat showed 2.0% seropositivity (p = 0.015). CONCLUSIONS: In Korea, the seroprevalence of B. henselae is higher than expected, suggesting that Bartonella infection due to B. henselae is not uncommon. Cats are proposed to play a more important role than dogs in transmission of CSD.

In Vitro Activity of Tigecycline Against Orientia tsutsugamushi.

Scrub typhus is a zoonosis caused by Orientia tsutsugamushi (O. tsutsugamushi) occurring mainly in autumn in Korea. The need of new antibiotics has arisen with a report on strains resistant to antibiotics and chronic infection. This study aims to identify susceptibility of tigecycline in-vitro as a new therapeutic option for O. tsutsugamushi. Antibacterial activity of tigecycline against the O. tsutsugamushi was compared with doxycycline using flow cytometry assay. The inhibitory concentration 50 (IC50) was 3.59×10⁻³ µg/mL in doxycycline-treated group. Whereas in 0.71×10⁻³ µg/mL tigecycline-treated group. These findings indicate that tigecycline may be a therapeutic option for the treatment of scrub typhus.

Bartonella henselae infection presenting with a picture of adult-onset Still's disease.

We report a patient with a clinical picture of suggestive for adult-onset Still's Disease (ASOD) due to Bartonella infection. A 42-year-old immunocompetent man was admitted with fever, rash, arthralgia and sore throat. As his clinical picture suggested ASOD except unusual skin manifestation, we treated him on steroid and ibuprofen. His fever and constitutional symptoms responded immediately within 24hrs of commencing therapy, yet rash and leukocytosis remained. Meanwhile, Bartonella infection was proved by culture of bone marrow. Minocyclin treatment started combined with hydroxychloroquine sulfate and the patient discharged with overall improvement.

Identification of Outer Membrane Vesicles Derived from Orientia tsutsugamushi.

Orientia tsutsugamushi, a causative pathogen of Scrub typhus, is a gram-negative intracellular bacterium. Outer membrane vesicles (OMVs) are produced from the membrane of bacteria and play many roles related to the survival of the pathogen. However, there have been no reports confirming whether O. tsutsugamushi indeed produce OMVs. O. tsutsugamushi boryong was cultured in ECV-304 cells for the purification of OMVs. Western blot analysis and immunoenrichment using anti-O. tsutsugamushi monoclonal antibody and electron microscopy were employed for identification and characterization of OMVs. We confirm the presence of OMVs derived from O. tsutsugamushi, and also found that those OMVs contain a major surface antigen of 56-kDa protein and variant immunogenic antigens.

In vitro Antagonism between Cefotaxime and Anti-Rickettsial Antibiotics against Orientia tsutsugamushi.

We have investigated the in vitro antimicrobial effects of antibiotic combinations against Orientia tsutsugamushi, the causative agent of scrub typhus. ECV304 cells were infected with the Boryong strain of O. tsutsugamushi and incubated in a medium containing doxycycline (4 µg/mL), azithromycin (0.5 µg/mL), rifampin (4 µg/mL), ciprofloxacin (25 µg/mL), gentamicin (5 µg/mL), cefotaxime (2 µg/mL), or combinations of these agents for 7 days, after which immunofluorescent staining for O. tsutsugamushi was performed. The percentages of infective foci in cultures containing antibiotics compared to those in cultures without antibiotics were 6.2% for doxycycline, 9.6% for azithromycin, 8.8% for rifampin, 96.6% for cefotaxime, 29.7% for doxycycline plus cefotaxime, 23.6% for azithromycin plus cefotaxime, and 41.4% for rifampin plus cefotaxime. These findings show an in vitro antagonism between anti-rickettsial agents and cefotaxime against O. tsutsugamushi. These results suggest that the efficacy of antibiotic combinations involving cefotaxime for the treatment of patients with scrub typhus, particularly those with severe pneumonia, needs to be investigated.

A case series of possibly recrudescent Orientia tsutsugamushi infection presenting as pneumonia.

Orientia tsutsugamushi remains latent in humans after scrub typhus. Pneumonia occurs as a complication of scrub typhus in the late-phase disease. However, pneumonia may also occur as a presenting manifestation of O. tsutsugamushi infection. We reviewed the cases of 3 patients with atypical pneumonia who presented at our hospital and were later confirmed to have O. tsutsugamushi infection by serology, nested polymerase chain reaction (PCR), and cell culture. All patients were young adults with no history of scrub typhus, and none claimed to have recently been exposed to areas where scrub typhus is endemic. Two cases occurred in non-outbreak seasons. Furthermore, eschar was not observed. Pneumonia was documented within 4 days after fever onset. The immunoglobulin (Ig) G antibody titers against O. tsutsugamushi were higher than the IgM titers, although the serologic test results were less helpful in the diagnosis. Nested PCR and cell culture of blood specimens confirmed the diagnosis of O. tsutsugamushi infection. These findings suggest that pneumonia can occur as a result of recrudescence of latent O. tsutsugamushi infection.

In vitro bacteriostatic effects of rifampin on Orientia tsutsugamushi.

We performed an in vitro cell culture experiment to ascertain whether rifampin exhibits bactericidal effects against Orientia tsutsugamushi, the causative agent of scrub typhus. ECV304 cells were infected with the Boryong or AFSC-4 strain of O. tsutsugamushi and then, the cultures were maintained in media with increasing concentrations of rifampin, azithromycin, doxycycline, or chloramphenicol for 4 days. On day 5, the media were replaced with fresh antibiotic-free medium and the cultures were maintained until day 28. On days 5, 13, and 28, immunofluorescence (IF) staining of O. tsutsugamushi was performed. IF staining on days 13 and 28 revealed increasing numbers of IF-positive foci in all cultures, even in cultures initially exposed to the highest concentration of rifampin (80 µg/mL), azithromycin (80 µg/mL), doxycycline (20 µg/mL), or chloramphenicol (100 µg/mL). The present study reveals that rifampin has no bactericidal effect against O. tsutsugamushi as observed for azithromycin, doxycycline, and chloramphenicol. A subpopulation of the bacteria that are not killed by high concentrations of the antibiotics may explain the persistence of O. tsutsugamushi in humans even after complete recovery from scrub typhus with antibiotic therapy.

High In Vitro Infectivity of a Doxycycline-Insensitive Strain of Orientia tsutsugamushi.

We compared the infectivity and growth rates of 12 strains of Orientia tsutsugamushi in a cell culture system. ECV304 cells were infected with O. tsutsugamushi strains for 4 hr, and the culture was maintained for 72 hr. Immunofluorescence (IF) staining was performed at 4, 24, 48, and 72 hr after inoculation (hpi), and IF-positive foci were enumerated. The AFSC-4 strain, which is known to be insensitive to doxycycline, showed higher numbers of IF-positive foci than the other 11 strains at 4, 24, 48, and 72 hpi, which may explain its apparent insensitivity to antibiotics.

First Case of Bartonella henselae Bacteremia in Korea.

Bartonella henselae causes cat-scratch disease, bacteremia, and various focal infections. Despite the worldwide occurrence of B. henselae infections, reports in humans are rare in Korea. The clinical manifestation of all 5 previously reported cases was lymphadenopathy. Herein, we report a case of bacteremia in a woman who presented with prolonged fever. B. henselae was isolated from a blood specimen by cell culture. Conventional polymerase chain reaction amplification and sequencing of the 16S-23S rRNA intergenic space region confirmed the isolate to be B. henselae. The patient had no underlying immunocompromising conditions and no recent exposure to animals. She was successfully managed with a combination of doxycycline and hydroxychloroquine.

Novel polysaccharide antigen of Orientia tsutsugamushi revealed by a monoclonal antibody.

Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular bacterium that replicates in the cytosol of host cells. Although several protein antigens have been characterized and cloned, little information exists regarding the polysaccharide antigen of this bacterium. In this study, we identified and characterized a novel antigen defined by a monoclonal antibody (MAb), NT19, against O. tsutsugamushi. Immunofluorescence microscopic studies showed that the NT19 antigen is released from the bacteria in the cytosol of host cells forming aggregates with bacteria. Immunoblot analysis showed that MAb NT19 recognized a strong band with a molecular mass of 20 kDa that was resistant to proteinase K digestion and sensitive to periodate oxidation, suggesting that the NT19 antigen is a polysaccharide. The function of this polysaccharide is not known, but considering its distribution within a bacterial microcolony, it is suspected to be involved in forming a biofilm-like structure within host cells.