Evaluation of recorded video-observed therapy for anti-tuberculosis treatment.

BACKGROUND: Asynchronous video directly observed therapy (VDOT) may reduce tuberculosis (TB) program costs and the burden on patients. We compared VDOT performance across three cities in the United States, each of which have TB incidence rates above the national average.METHODS: Patients aged ≥18 years who are currently receiving directly observed anti-TB treatment were invited to use VDOT for monitoring treatment. Pre- and post-treatment interviews and medical records were used to assess site differences in treatment adherence and patient characteristics and perceptions.RESULTS: Participants were enrolled in New York City, NY (n = 48), San Diego, CA (n = 52) and San Francisco, CA, USA (n = 49). Overall, the mean age was 41 years (range 18-87); 59% were male; most were Asian (45%) or Hispanic/Latino (30%); and 77% were foreign-born. The median fraction of expected doses observed (FEDO) was 88% (IQR 76-96). At follow-up, 97% thought VDOT was "very or somewhat easy to use" and 95% would recommend VDOT to other TB patients. Age, race/ethnicity, annual income, and country of birth differed by city (P < 0.05), but FEDO and VDOT perceptions did not.CONCLUSIONS: TB programs in three large US cities observed a high FEDO using VDOT while minimizing staff time and travel. Similar findings across sites support VDOT adoption by other large, urban TB programs.

Magnitude of Mycobacterium tuberculosis transmission among household and non-household contacts of TB patients.

The household and non-household contacts of patients with tuberculosis (TB) face varying degrees of risk of infection by Mycobacterium tuberculosis. To quantify new infection and to determine the risk factors associated with new infection among named contacts in San Francisco, CA, USA. We performed a cohort study in patients with culture-positive pulmonary TB. We analyzed patient, contact, environmental and bacterial characteristics. Of the 2422 contacts named by 256 patients, 149 (6.2%) had new infection due to recent transmission from 79 (30.9%) patients. Of the 149 new infections, 87 (58.4%) occurred among household contacts and 62 (41.6%) among non-household contacts. Numerous acid-fast bacilli in sputum (odds ratio [OR] 2.64, 95%CI 1.32-5.25) and contacts being named by more than one patient (OR 2.90, 95%CI 1.23-6.85) were associated with new infection among household contacts. Being older than 50 years (OR 1.93, 95%CI 1.09-3.41) and an Asian/Pacific Islander (OR 3.09, 95%CI 1.50-6.37) were associated with new infection among non-household contacts. Fewer than one third of patients caused new infection to his/her contacts. A substantial proportion of transmission resulting in new infection occurred outside of the household. The risk factors for infection among household and non-household contacts are different and should be considered when prioritizing control interventions. .

Impact of Euro-American sublineages of Mycobacterium tuberculosis on new infections among named contacts.

BACKGROUND: The impact of demographic, clinical, and bacterial factors on new infection by Euro-American lineage Mycobacterium tuberculosis among contacts of patients with tuberculosis (TB) has not been evaluated. OBJECTIVE: To describe the risk factors for new infection by Euro-American M. tuberculosis sublineages in San Francisco, California. DESIGN: We included contacts of patients with TB due to Euro-American M. tuberculosis. Sublineages were determined by large-sequence polymorphisms. We used tuberculin skin testing or QuantiFERON®-TB Gold In-Tube to identify contacts with new infection. Regression models with generalized estimating equations were used to determine the risk factors for new infection. RESULTS: We included 1488 contacts from 134 patients with TB. There were 79 (5.3%) contacts with new infection. In adjusted analyses, contacts of patients with TB due to region of difference 219 M. tuberculosis sublineage were less likely to have new infection (OR 0.23, 95%CI 0.06-0.84) than those with other sublineages. Other risk factors for new infection were contacts exposed to more than one patient with TB, contacts exposed for 30 days, or contacts with a history of smoking or excessive alcohol consumption. CONCLUSIONS: In addition to well-known exposure and clinical characteristics, bacterial characteristics independently contribute to the transmissibility of TB in San Francisco.

Reduced sensitivity of the QuantiFERON(®) test in diabetic patients with smear-negative tuberculosis.

SETTING: Immunosuppressive conditions have been associated with low sensitivity of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) for the diagnosis of tuberculosis (TB). However, no systematic analysis of patient and bacterial characteristics has been performed before. OBJECTIVE: To determine the sensitivity and the risk factors for false-negative QuantiFERON(®)-TB (QFT) assay and TST in TB patients. DESIGN: We performed a retrospective analysis of data collected in a community-based study of TB in San Francisco, CA, USA. We included 300 TB patients who underwent QFT and TST. RESULTS: The risk factors for false-negative QFT were human immunodeficiency virus infection and the use of QuantiFERON(®)-TB Gold. In patients with sputum smear-negative TB, diabetes mellitus (DM) was associated with false-negative QFT (OR 2.85, 95%CI 1.02-7.97, P = 0.045). TST sensitivity was higher than QFT sensitivity in DM patients (OR 9.46, 95%CI 2.53-35.3). CONCLUSIONS: In San Francisco, QFT sensitivity was lower than that of TST, especially in patients with DM. Stratified analysis by sputum smear results showed that this association was specific to smear-negative TB. In contrast, TST was not affected by the presence of DM.

Platelet-derived microparticles on synthetic surfaces observed by atomic force microscopy and fluorescence microscopy.

Platelet activation on a thrombogenic surface includes the release of membrane-derived microparticles that provide catalytic sites for blood coagulation factors. Here, we describe a quantitative investigation on the production and dimensions of platelet-derived microparticles observed on glass and polyethylene under aqueous conditions, using atomic force microscopy (AFM) and complementary fluorescence microscopy. The results show that contact-activated platelet microparticles are not evenly distributed over a thrombogenic surface, but in clusters in close proximity to adherent platelets. The microparticles are localized near the platelet periphery, and in some cases appear to emanate from platelet pseudopodia, suggesting that formation may result from vesiculation of the pseudopodia. The microparticles measured 125 +/- 21 nm (n = 73) in the x-y dimensions and 5.2 +/- 3.6 nm in height. The results compared closely with 125 +/- 22 nm width and 4.1 +/- 1.6 nm height obtained for control preparations of thrombin activated microparticles, that were filtered and deposited on glass. Large differences between the measured widths and heights of adsorbed microparticles suggest that platelet microparticles may undergo spreading after attachment to a surface. The adsorbed microparticles expressed platelet membrane receptor GPIIb/IIIa, and many expressed the platelet activation marker P-selectin as determined by fluorescence microscopy. The high number distribution of procoagulant microparticles per unit area of surface compared with platelets suggests that platelet-derived microparticles provide a mechanistic route for amplifying thrombus formation on a thrombogenic surface.

Bacterial surface properties of clinically isolated Staphylococcus epidermidis strains determine adhesion on polyethylene.

The role of surface physiochemical properties of Staphylococcus epidermidis strains in adhesion to polyethylene (PE) was investigated under physiological flow conditions in phosphate buffered saline (PBS) and 1% platelet poor plasma (PPP). Four clinically isolated strains were divided into two groups: low and high relative hydrophobicity, and the F1198 and RP62A strains showing significantly greater hydrophobicity than the F21 and F1018 strains. In PBS, adhesion of all S. epidermidis strains was shear dependent from 0 to 15 dyn/cm2, after which adhesion becomes shear independent. Strains with higher surface hydrophobicity showed higher adhesion to PE, demonstrating the influence of bacterial surface hydrophobicity in nonspecific adhesion. Bacterial adhesion correlated well with bacterial surface hydrophobicity at low shear stresses (0-8 dyn/cm2). In 1% PPP, adhesion of all strains dramatically decreased and we found no correlation between bacterial surface hydrophobicity and adhesion. The presence of plasma proteins reduced nonspecific adhesion. S. epidermidis surface charge did not correlate with bacterial adhesion in either test media. The results suggested that S. epidermidis surface hydrophobicity may mediate nonspecific adhesion to PE at low shear stresses in protein-free media.

Occurrence of Erysipelothrix spp. in chicken meat parts from a processing plant.

From March 1996 to March 1997, 153 domestic raw chicken meat samples, including 71 thigh, 50 outer breast muscle, and 32 white meat samples, from a processing plant located in a chicken abattoir in Nagano Prefecture, Japan, were examined for the presence of Erysipelothrix spp. Erysipelothrix spp. were isolated from 49 (30.0%) of the 153 chicken meat samples. Of 67 Erysipelothrix isolates, 65 and 2 isolates were identified as E rhusiopathiae and E. tonsillarum. E. rhusiopathiae and E. tonsillarum isolates were serotyped into 11 and 2 different serovars, respectively. These findings might indicate that domestic chicken meat is frequently contaminated with E. rhusiopathiae and seems to be a potential source of human Erysipelothrix infection.

Occurrence of Erysipelothrix spp. in broiler chickens at an abattoir.

From September 1995 to August 1996, 750 chickens from 66 farms sent to an abattoir in Nagano Prefecture, Japan, were examined for the presence of Erysipelothrix spp. Erysipelothrix spp. were isolated from 118 (15.7%) of 750 skin samples, 27 (7.3%) of 372 hypoderm samples, 12 (1.9%) of 630 throat samples, 106 (59.2%) of 179 feather samples, and none of 257 spleen samples. Of 66 farms, 55 farms (83.3%) sent Erysipelothrix-positive chickens and 11 farms (16.7%) only negative ones. Of 297 Erysipelothrix isolates, 273 isolates were identified as Erysipelothrix rhusiopathiae and 24 as Erysipelothrix tonsillarum. E. rhusiopathiae isolates were serotyped into nine different serovars. Of the 273 E. rhusiopathiae isolates, 33 (11.1%) were serotyped to serovar 6; 22 (7.4%) were serovar 5; 19 (6.4%) were serovar 2; 15 (5.1%) were serovar 8; 2 (0.7%) were serovar 21; 4 each (1.3% each) were serovars 1b, 9, 12, and 19; and 178 (59.9%) were untypeable. Of 24 E. tonsillarum isolates, 15 (5.1%) were serotyped to serovar 3, and 9 (3.0%) were serovar 7. These findings indicate that chickens seem to be a potential reservoir of Erysipelothrix spp. in nature and to be a source of human Erysipelothrix infection.

Adhesion of Staphylococcus epidermidis and transposon mutant strains to hydrophobic polyethylene.

Staphylococcus epidermidis capsular polysaccharide adhesin (PS/A) and slime were studied as possible mediators of bacterial adhesion to NHLBI polyethylene (PE) under dynamic flow. This putative interaction was examined by quantifying the adhesion of M187 (PS/A+, slime+) parent strain and isogenic transposon mutant strain sn3 (PS/A-, slime-) to polyethylene (PE) under a range of physiologic shear stress conditions in both phosphate-buffered saline (PBS) and 1% platelet poor plasma (PPP). No significant differences in adhesion were noted between the M187 and sn3 strains in either test medium. However, adhesion of both strains in 1% PPP was decreased 75-95% compared to adhesion in PBS. In PBS, adhesion was shear stress dependent from 0-15 dyne/cm2, after which adhesion was comparatively shear stress independent. Adhesion in 1% PPP was independent of shear stress. Epifluorescent imaging of both strains labeled for slime confirmed the presence of slime on the surface of M187 and suggested that PS/A and slime promote the formation of large aggregates, as aggregates were totally absent in the images of the sn3 strain. The results suggest that PS/A and slime do not mediate S. epidermidis adhesion to bare PE or PE with adsorbed plasma proteins, but may be necessary for intercellular adhesion, which is important for biofilm formation.

The presence of antibodies to purified p24gag protein of HTLV-I in sera of patients with systemic lupus erythematosus (SLE).

Sera of patients with systemic lupus erythematosus (SLE) were tested for their reactivity to HTLV-I by western blotting (WB). Seven (18%) of 40 SLE serum samples reacted to the p24gag protein of HTLV-I by WB using purified gag antigens. The specificity of anti-p24gag antibodies in the SLE sera was confirmed by competitive inhibition on WB. Two of the seven patients were shown to be HTLV-I carriers, because HTLV-I infected T cell lines were easily established from their peripheral blood mononuclear cells (PBMC). Except for these two carrier patients, the gag proteins were not detected in the lysates of PBMC by WB using anti-p24gag and anti-p19gag monoclonal antibodies. The gag and pX genes of HTLV-I were not detected by PCR in PBMC of the SLE patients, with the exception of the 2 HTLV-I carrier patients. These results show no direct involvement of HTLV-I in the etiology of SLE. However, the existence of a specific antibody to p24gag in the sera of some of the noncarrier SLE patients suggests a crossreactivity to either unknown viruses or some autoantigens.

A possible contribution of phospholipids in tissue distribution of quinidine in rats.

The tissue distribution of quinidine was investigated at three different steady-state plasma concentrations of quinidine in rats. The tissue distribution of quinidine (tissue-to-plasma concentration ratio, Ct/Cp) was studied in the liver, lung, kidney and heart and the highest distribution was found in the lung. Tissue binding characteristics of quinidine was determined in normal tissue homogenates and lipid-depleted tissue homogenates in vitro. No correlation was observed between the tissue bindings (product of association constant (K1) and number of binding sites (n), nK1) estimated in each normal tissue homogenate and the values of Ct/Cp in vivo. However, a marked decrease in the tissue binding of quinidine was observed in all lipid-depleted tissue homogenates, and the largest decrease was observed in the lung tissue. This result suggested that lipid may have an important role in the tissue binding of quinidine. However, no good relationship was observed between the values of Ct/Cp and the phospholipid contents in each tissue. In order to investigate the role of lipid in the tissue binding of quinidine, phospholipids extracted from each tissue were used for binding study. The phospholipids binding of quinidine (nK2) increased in the following order; heart less than liver less than kidney less than lung, and the plots of the values of Ct/Cp obtained in vivo against the binding ability of phospholipids (product of nK2 and the content of phospholipid in each tissue) gave a good linear relationship. Based on these observations, it was concluded that some species of phospholipids had an important and determining role in the tissue distribution of quinidine in vivo.

Pupillary analyses in Graves' disease.

Using electronic videopupillography, the direct pupillary response to light and edge light pupillary oscillation by slit light stimulus was examined in patients with hyperthyroidism and in controls. Amplitude of constriction, velocities of constriction and dilatation significantly reduced in the patients in pupillary response to light. The pupillary oscillation was also reduced in the amplitude of oscillation as well as in the velocities of dilatation and constriction. These alterations in pupillary response to light correlated only with the triiodothyronine-RSU test. The oscillation correlated with the duration of the disease. The results indicated that the pupil dynamics were abnormal in patients with hyperthyroidism and this can be demonstrated by sensitive pupillography.

Hypersensitivity to hydrogenated lanolin.

The number of patients with dermatitis from applied betamethasone-17-valerate ointment, which incorporated hydrogenated lanolin, rapidly increased in Japan after 1971. On patch testing, the incidence of hypersensitivity to hydrogenated lanolin is significantly higher than to anhydrous lanolin at the 1% level, that is 5.20% (26/502) with the former and 1.99% (10/502) with the latter, although sensitivity to both materials is significantly related at the 0.5% level. The possible explanations considered are that hydrogenated lanolin contains three main allergens: the first is a group of lanolin alcohols which are the common eczematogens in anhydrous lanolin; the second refers to the products of hydrogenation, composed of saturated, easily oxidized, organic substances of low molecular weight; and the third refers to traces of nickel, copper and chromium, as a result of contamination in the hydrogenation process.