[Two cases of pulmonary aspergilosis, which deteriorated with generic itraconazole].

We experienced two cases of pulmonary aspergillosis, which deteriorated during treatment with generic itraconazole (ITCZ) because of low plasma concentration. One case was chronic pulmonary aspergillosis and the other was allergic bronchopulmonary aspergillosis (ABPA). Treatment of both cases was started with a brand-name-ITCZ, and changed to a generic ITCZ. Deterioration of pulmonary aspergillosis occurred after 8 months and 9 months from change to generic ITCZ respectively. In the first case, the ITCZ-plasma concentration was 46.9 ng/mL and of OH-ITCZ 96.5 ng/mL with generic ITCZ at the dose of 300 mg/day, but increased to 1,559.7 ng/mL and to 2,485.0 ng/mL with the brand-name-ITCZ 300 mg/day, respectively. In the second case, the ITCZ-plasma concentration was 27.2 ng/mL and of OH-ITCZ 20.1 ng/mL with 150 mg/day for generic ITCZ, but reached 857.3 ng/mL and to 1,144.2 ng/ml with the brand-name-ITCZ 300 mg/day, respectively. After treatment failure, the first case was changed to voriconazole, then brand-name-ITCZ 300 mg/day, and the second case to the brand-name-ITCZ 300 mg/day, with successful clinical course. Plasma concentrations of ITCZ can differ significantly depending on the patient or type of ITCZ. The ITCZ-plasma concentration should be controlled after changing from a brand-name-ITCZ to a generic ITCZ.

In Vivo Quantitative Ultrasound on Dermis and Hypodermis for Classifying Lymphedema Severity in Humans.

This study investigated the ability of in vivo quantitative ultrasound (QUS) assessment to evaluate lymphedema severity compared with the gold standard method, the International Society of Lymphology (ISL) stage. Ultrasonic measurements were made around the middle thigh (n = 150). Radiofrequency data were acquired using a clinical scanner and 8-MHz linear probe. Envelope statistical analysis was performed using constant false alarm rate processing and homodyned K (HK) distribution. The attenuation coefficient was calculated using the spectral log-difference technique. The backscatter coefficient (BSC) was obtained by the reference phantom method with attenuation compensation according to the attenuation coefficients in the dermis and hypodermis, and then effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were estimated with a Gaussian model. Receiver operating characteristic curves of QUS parameters were obtained using a linear regression model. A single QUS parameter with high area under the curve (AUC) differed between the dermis (ESD and EAC) and hypodermis (HK) parameters. The combinations with ESD and EAC in the dermis, HK parameters in the hypodermis and typical features (dermal thickness and echogenic regions in the hypodermis) improved classification performance between ISL stages 0 and ≥I (AUC = 0.90 with sensitivity of 75% and specificity of 91%) in comparison with ESD and EAC in the dermis (AUC = 0.82) and HK parameters in the hypodermis (AUC = 0.82). In vivo QUS assessment by BSC and envelope statistical analyses can be valuable for non-invasively classifying an extremely early stage of lymphedema, such as ISL stage I, and following its progression.

Upside-down gliding of Lymnaea.

The pond snail Lymnaea stagnalis can often be observed moving upside down on its back just below the surface of the water. We have termed this form of movement "upside-down gliding." To elucidate the mechanism of this locomotion, we performed a series of experiments involving behavioral analyses and microscopic observations. These experiments were designed (1) to measure the speed of this locomotion; (2) to determine whether the mucus secreted from the foot of Lymnaea repels water, thereby allowing the snail to exploit the surface tension of the water for upside-down gliding; and (3) to observe the beating of foot cilia in this behavior. The beating of these cilia is thought to be the primary driving force for upside-down gliding. Our results demonstrate that upside-down gliding is an efficient active process involving the secretion of mucus that floats up to the water surface to serve as a substrate upon which cilia beat to cause locomotion at the underside of the water surface.

Speed of back-swimming of Lymnaea.

The pond snail, Lymnaea stagnalis, can locomote on its back utilizing the surface tension of the water. We have called this form of movement 'back-swimming'. In order to perform this behavior, the snail must flip itself over on its back so that its foot is visible from above. Little is known about the mechanism of this back-swimming. As a first step for the elucidation of this mechanism, we measured the speed of back-swimming of Lymnaea at the different times of the day. They back-swam significantly faster in the morning than just before dark. These data are consistent with our earlier findings on circadian-timed activity pattern in Lymnaea. Lymnaea appear to secrete a thin membrane-like substance from their foot that may allow them to back-swim. To confirm the existence of this substance and to examine whether this substance is hydrophobic or hydrophilic, we applied a detergent onto the foot during back-swimming. A single drop of 1% Tween 20 drifted Lymnaea away that were still kept at the water surface. These results suggest that Lymnaea secrete a hydrophobic substance from their foot that floats to the water surface allowing Lymnaea to back-swim.

Outcomes in HIV-infected patients on antiretroviral therapy with tuberculosis.

HIV-infected patients with active tuberculosis (TB) having CD4 counts < 100/mm3 and who were antiretroviral therapy (ART) naïve were reviewed retrospectively to determine the outcomes of their tuberculosis infection. All patients received ART at or after receiving anti-TB treatment. Clinical manifestations, treatment regimens and outcomes were analyzed. Of 101 patients, 62 (61.4%) completed TB treatment. Of these, 53.2% were treated with a 6-month standard TB regimen, while the rest were treated with prolonged TB regimens. The median interval between anti-TB treatment and ART was 68 days (range: 0-381). Among the clinically cured patients 66.1% received rifampin concomitantly with nevirapine, and 32.3% received rifampin concomitantly with efavirenz. The treatment success rate was 75.6%, with a mortality rate of 6.1%. The risk factors for death were resistant TB (p = 0.03) and poor compliance (p < 0.05). Seven point nine percent had multi-drug resistant TB. Possible or probable immune reconstitution inflammatory syndrome (IRIS) was seen in 15 cases (14.9%). No life-threatening IRIS was reported, and it did not affect disease outcome (p = 0.5). A shorter time between anti-TB treatment and ART onset was associated with the occurrence of IRIS (31 days vs 90 days; p < 0.05). Regarding adverse drug effects, 44.6% had side effects due either to anti-TB drugs or ART. Sixty-six point one percent of them occurred within the first 2 months of TB treatment, and 43 (76.8%) had to stop or change either anti-TB treatment or ART. The mortality rate with TB and HIV on ART was low and the occurrence of IRIS did not carry any additional mortality.

[Capsular polysaccharide antibodies after pneumococcal polysaccharide vaccination in patients with chronic respiratory disease].

We investigated the antibody response to a 23-valent pneumococcal polysaccharide vaccine (23PSV), in 151 patients (average age: 70 years old) with chronic respiratory disease. Serotype-specific IgG antibodies to 4 pneumococcal capsular polysaccharides (6B, 14, 19F, and 23F) were analyzed by ELISA before, and one month after, 23PSV vaccination in all patients. Patients showed a significant increase in specific IgG levels to Streptococcus pneumoniae after 23PSV vaccination (5.5 times-20.9 times). Even patients aged over 80, patients with respiratory failure, and patients receiving corticosteroid therapy developed a significant immunologic response to 23PSV. Local pain or induration occurred in 9.1-14.3% and fatigue or chills occurred in 0.7-6.5% of patients. All adverse reactions disappeared in 2 or 3 days and there was no severe adverse events. Further studies are needed to confirm the exact protective antibody level and to examine the decline of antibody level after vaccination.

[Characteristics and treatment outcomes of INH-resistant or RFP-resistant tuberculosis].

BACKGROUND: As an effective regimen for isoniazid-resistant but rifampicin-susceptible tuberculosis (INHr-TB), the use of a 6-month three or four-drug treatment regimen including refampicin (or rifampin) and pyrazinamide has been recommended by many experts of the world. On the other hand, treatment regimen for rifampicin-resistant but isoniazide-susceptible tuberculosis (RFPr-TB) has not been well established because of the small number of such patients. In Japan the standard regimen has not been established even for INHr-TB, and the treatment has been done by each physician on the empirical bases. OBJECTIVES: To determine the adequate therapy of INH-resistant TB or RFP-resistant TB. DESIGN: Retrospective cohort study. SUBJECTIVES: Hundred and eleven INHr-TB patients (4.9%) and 5 RFPr-TB patients (0.2%) out of 2252 new smear-positive tuberculosis patients who were admitted to our hospital from 1994 to 1998. RESULTS: Patients with previous tuberculosis history was found in 35 of 111 INHr-TB (31.5%) patients, of which 13 (37.1%) were re-treated within 3 years. On the other hand 146 patients (21.1%) of all new culture-positive tuberculosis patients (N = 690) treated in our hospital from 1997 to 1999 had the previous tuberculosis history of which only 8 patients (5.5%) were retreated within 3 years while 115 patients relapsed more than 10 years after the onset of previous tuberculosis history. The frequency of recurrence within 3 years after the onset of previous tuberculosis history was, significantly higher (p < 0.0001) in cases of INHr-TB (13/111 [11.7%]) than in cases of newly registered ones (8/690 [1.2%]), and the fact indicates that the incidence of tuberculosis recurrence was higher in INHr-TB patients than in pan-sensitive TB patients when the previous treatment was discontinued or insufficiently implemented. The resistance pattern of the INHr-strains were as follows. INH alone 40 (36.0%), SM-resistant 47 (42.3%), TH resistant 19 (17.1%), EB-resistant 18 (16.2%), KM-resistant 6 (5.4%), and others 3 (2.7%). Therefore the mean number (+/- SD) of resistant drugs excluding INH was 1.4 +/- 0.7. Eighteen out of 71 (25.4%) strains with low grade INH-resistance (0.1 microgram/ml complete resistance) had also TH-resistance, while only one out of 40 (2.5%) strains with high grade INH-resistance (1 microgram/ml resistance) was resistant to TH (p = 0.005). Of 111 INHr-TB patients, 9 patients (8.1%) discontinued treatment by themselves, 17 patients (15.3%) admitted to another hospital, and 17 patients (15.3%) died. The patients who died (age [M +/- SD] 66.4 +/- 14.0 yrs) were older than those who were alive (48.7 +/- 17.8, p < 0.001), and were too seriously ill to accept sufficient chemotherapy, and therefore their deaths were not considered to be related to INH resistance. The treatment outcomes of the remaining 68 patients who were followed in our hospital were summarized as follows. 1) Treatment failure occurred in 3 patients, of whom 2 patients could not be treated with full dose rifampicin in the initial phase of treatment because of side effects to liver or accompanying idiopathic thrombocytepenic purpura (ITP). Two out of these 3 patients developed multi-drug resistant tuberculosis (MDR-TB). Success rate of treatment was 65/68 (95.6%). 2) Alterations of regimens after knowing INHr-TB were done in 41 of 65 patients (63.0%) with treatment success in all cases. The susceptible drugs used were 65 (100%) for RFP, 62 (95.4%) for EB, 23 (35.4%) for PZA, 26 (40.0%) for SM, 32 (49.2%) for new quinolone (NQ). 3) The sputum culture conversion rates two months after starting chemotherapy with (N = 16) and without (N = 52) PZA were 13/16 (81.3%) and 31/52 (59.6%), respectively. 4) After the completion of treatment, relapse occurred in 4 patients during follow-up period (1-39 months). The recurrence occurred in 3 out of 20 patients (15%) treated with INH and two susceptible drugs, none out of 13 with three susceptible drugs (0%), 1 out of 20 with INH and three susceptible drugs (5%), and none out of 11 with more than 4 susceptible drugs (0%), and the fact indicates that there was no significant advantage to add INH of usual dose to the regimens. 5) The durations of treatment were not less than 9 months except one case. When 3 or more susceptible drugs were used, the recurrence rate in the group of treatment duration 9-12 months was 0/12 and that in the group of treatment duration more than 12 months was 1/33. Even in the groups without PZA in the initial 2 months of treatment, the recurrence rate in the group of treatment duration 9-12 month was 0/8, and that in the group of treatment duration more than 12 months was 0/22. The fact indicates that 12 months therapy was sufficient irrespective of the use of PZA. 6) One of 5 RFPr-TB patients discontinued treatment by himself. Remaining 4 patients were treated by 4.5 +/- 0.5 susceptible drugs including INH for more than 20 months (21.7 +/- 2.8 months) after sputum culture conversion with the successful result of treatment and no relapses during the followup period for 3-60 months. CONCLUSION: For INHr-TB, even when PZA can't be used because of adverse effects or resistance, 3 or 4 susceptible drugs regimens including RFP for 12 months were effective. For RFPr-TB, the treatment with 4 or more susceptible drugs for 20 months after sputum culture conversion might be adequate.

Establishment and clinical applications of a portable system for capturing influenza viruses released through coughing.

Coughing plays an important role in influenza transmission; however, there is insufficient information regarding the viral load in cough because of the lack of convenient and reliable collection methods. We developed a portable airborne particle-collection system to measure the viral load; it is equipped with an air sampler to draw air and pass it through a gelatin membrane filter connected to a cone-shaped, megaphone-like device to guide the cough airflow to the membrane. The membrane was dissolved in a medium, and the viral load was measured using quantitative real-time reverse transcriptase-polymerase chain reaction and a plaque assay. The approximate viral recovery rate of this system was 10% in simulation experiments to collect and quantify the viral particles aerosolized by a nebulizer. Using this system, cough samples were collected from 56 influenza A patients. The total viral detection rate was 41% (23/56), and the viral loads varied significantly (from <10, less than the detection limit, to 2240 viral gene copies/cough). Viable viruses were detected from 3 samples with ≤18 plaque forming units per cough sample. The virus detection rates were similar among different groups of patients infected with different viral subtypes and during different influenza seasons. Among patients who did not receive antiviral treatment, viruses were detected in one of six cases in the vaccinated group and four of six cases in the unvaccinated group. We found cases with high viral titers in throat swabs or oral secretions but very low or undetectable in coughs and vice versa suggesting other possible anatomical sites where the viruses might be mixed into the cough. Our system is easy to operate, appropriate for bedside use, and is useful for comparing the viral load in cough samples from influenza patients under various conditions and settings. However, further large-scale studies are warranted to validate our results.

Possible prevalence and transmission of acute respiratory tract infections caused by Streptococcus pneumoniae and Haemophilus influenzae among the internally displaced persons in tsunami disaster evacuation camps of Sri Lanka.

OBJECTIVE: The objective of this prospective study was to investigate the status of acute respiratory tract infections caused by Haemophilus influenzae and Streptococcus pneumoniae in tsunami disaster evacuation camps. METHODS: Nasopharyngeal swabs (NP) of 324 internally displaced persons (IDP) in 3 different tsunami disaster evacuation camps of Sri Lanka were collected between March 18th and 20th, 2005, and analyzed for MIC, beta-lactamase production, serotypes, PCR and pulsed-field gel electrophoresis (PFGE). RESULTS: Many IDP had respiratory symptoms and the prevalence of cough and/or sputum was 84%, 70.5% and 64.7% in the three camps. Twenty-one H. influenzae from 20 IDP and 25 S. pneumoniae from 22 IDP were isolated from the NP. All H. influenzae isolates were nontypeable, and 5 were beta-lactamase producing. Seventeen pneumococci were susceptible, 5 showed intermediate resistance and 3 were fully resistant to penicillin G. Molecular analysis showed the 21 H. influenzae strains had 13 PFGE patterns and 25 pneumococci had 16 PFGE patterns. All 4 different PFGE patterns of H. influenzae strains were detected in a few IDP in camps 1 and 3, and 5 different PFGE patterns of serotype 3, 22A, 9A, 10A and 11A pneumococci were detected in a few IDP in camps 1 and 3. CONCLUSION: Our data indicate acute respiratory tract infections caused by various types of H. influenzae and S. pneumoniae appear to have been prevalent, some of which were potentially transmitted from person to person in tsunami disaster evacuation camps.

Pulmonary anisakiasis presenting as eosinophilic pleural effusion.

A 63-year-old man developed a pleural effusion with marked eosinophilia, which was more prominent in the pleural fluid than in the peripheral blood. The pleural effusion spontaneously disappeared 7 days after admission. A multiple dot enzyme-linked immunosorbent assay for anisakiasis was strongly positive for both the serum and pleural fluid. The serum IgG titre for Anisakis simplex gradually decreased over 7 months. It is suspected that Anisakis larvae can penetrate the alimentary canal, and then migrate into the pleural cavity through the diaphragm. Screening with a serological test is useful in the diagnosis of this condition; human pulmonary anisakiasis.