The usefulness of lymphocyte stimulation test (LST) in side effects of antituberculosis drugs

PURPOSE: The usefulness of the lymphocyte stimulation test (LST) was examined in patients who arose side effects to antituberculosis drugs. METHODS: The usefulness of LST was examined in 36 patients from January, 1999 to July, 2002. RESULTS: There were 11 LST positive patients, and the LST positive rate was 30.6%. The causing agents determined by the LST positive patients were INH in 7, RFP in 3 and EB in one. The sensitivity of LST was 46.2% and the specificity of LST was 76.6%. CONCLUSION: LST positive rate of antituberculosis drugs was low and it was difficult to determine the causing drugs by LST.     

Testosterone patches in the management of patients with mild/moderate systemic lupus erythematosus

OBJECTIVES: Androgen deficiency has been associated with the development of systemic lupus erythematosus (SLE). The aim of this study was to test the efficacy of testosterone patches vs placebo in female SLE patients with baseline mild-to-moderate disease activity in a randomized, double-blind, single-centre placebo-controlled trial. METHODS: Patients received testosterone (150 microg) or placebo transdermal patches for 12 weeks. Patients were assessed at 4-weekly intervals for disease activity using the Safety of Oestrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI), Systemic Lupus Activity Measure-Revised (SLAM-R) and The British Isles Lupus Assessment Group (BILAG) indices, physician global assessment (PGA), quality of life using the SF-36 survey and sexual functioning using the Derogatis score. Data were analysed using two sample t-tests to compare the mean difference from baseline to week 12 in the testosterone patch and placebo groups. RESULTS: Thirty-four patients were recruited in to each group. There was no significant baseline difference between the groups in age, race or marital status. There was no significant difference between treatment groups in the mean change in SELENA-SLEDAI (0.547 +/- 3.72, P > 0.60), nor in PGA or BILAG system scores. The mean change in SLAM-R score was statistically different (2.06, S.D. 3.3, P = 0.01) but was not considered clinically meaningful. Health transition also showed a small change (P < 0.03). There was no significant difference in the Derogatis scores or toxicity. CONCLUSIONS: Testosterone patches were safe but did not significantly affect disease activity, quality of life or sexual functioning. Increased use of steroids in the placebo group may have confounded the study results.     

A case of Mycobacterium intracellulare pleurisy without active lung lesion

Pleural effusion without occurrence of active pulmonary lesion due to nontuberculous mycobacteria is extremely rare. We report a case of Mycobacterium intracellulare pleurisy in an 84-year-old woman. The patient was admitted to a nearby hospital because of dyspnea. Massive right pleural effusion was observed on chest roentgenogram. Bacteriological examinations, smear and culture of the sputum or pleural effusion were negative. First we thought pleurisy was caused by M. tuberculosis as pleural effusion showed predominant lymphocyte count and high adenosine deaminase level. However, M. intracellulare was identified by the polymerase chain reaction method from pleural effusion. Based on clinical findings and laboratory data, we suspected pleurisy was due to M. intracellulare infection. Clarithromycin, kanamycin, rifampicin and ethambutol were administered. After four months of treatment pleural effusion disappeared without accompanying the active pulmonary lesion. Therefore, we diagnosed this case as pleurisy without pulmonary lesion due to M. intracellulare.     

Quantiferon TB-2G among nurses with a history of working in our tuberculosis ward

PURPOSE: To investigate the infection rate of tuberculosis among nurses with a history of working in our hospital's tuberculosis ward (TW). METHODS: We measured interferon gamma levels in 50 nurses who had worked in our TW, and evaluated the infection rate among these nurses before (I) and after (II) the use of our hospital's tuberculosis infection control manual. RESULTS: The infection rate including probable infection was 6/50 (12.0%) in all TW nurses. The infection rate in the group I was 17.6%, but that in group II was 0%. CONCLUSION: Our hospital's tuberculosis infection control manual was effective for decreasing the infection rate, despite a high rate of infection in group I.     

A case of M. fortuitum lung disease with small-cell lung cancer]

A 58-year-old man was admitted to our hospital because of an abnormal shadow found on chest radiography. Chest radiographs and chest CT on admission showed a bulla with a niveau and infiltration in the right upper lobe. Smear of sputum and bronchial lavage were negative for acid-fast bacilli. Despite treatment with meropenem and clindamycin, the infiltrating shadow worsened. Since bronchial lavage and sputum culture were positive for M. fortuitum, these drugs were replaced with minocycline and imipenem. Thereafter, the shadow on the chest radiograph improved. After discharge, outpatient treatment with clarithromycin and levofloxacin was continued. After 4 months, the residual tumor shadow in the right upper lobe gradually grew. When a CT-guided transcutaneous needle lung biopsy was undertaken, malignant cells were found. Right upper lobectomy was performed. Pathological examination of the lesion demonstrated small-cell lung cancer. If a lesion does not change after nontuberculous mycobacteria treatment, the physician should consider other lesions such as lung cancer.     

A case of drug-induced pneumonia possibly associated with simvastatin]

A 59-year-old woman was admitted because of general fatigue, cough and progressive dyspnea about 5 months after treatment with simvastatin for hyperlipidemia. A chest radiograph and computed tomography scans revealed ground glass and reticular opacities in the right middle and lower lung fields. The percentage of peripheral blood eosinophils was elevated. After simvastatin was discontinued and administration of prednisolone was started, eosinophilia and reticular shadows improved. Drug lymphocyte stimulation test (DLST) for simvastatin was positive, so we diagnosed drug induced eosinophilic pneumonia. Now hyperlipidemia is treated frequently with HMG-CoA reductase inhibitor, but there are few reports demonstrating lung injury by this drug. We should be aware of lung side effects of HMG-CoA reductase inhibitor.     

Genetic evidence for Plasmodium falciparum resistance to chloroquine and pyrimethamine in Indochina and the Western Pacific between 1984 and 1998

Plasmodium falciparum resistance to chloroquine and pyrimethamine is widely distributed in malaria-endemic areas. The origin and geographic spread of this drug resistance have been inferred mainly from records of clinical resistance (treatment failure). Identification of the Plasmodium falciparum chloroqunie resistance transporter (pfcrt) gene and the dihydrofolate reductase (dhfr) gene as target genes of chloroquine and pyrimethamine, respectively, has made it possible to trace the history of genetic resistance to these two drugs. However, evidence for genetic resistance has been limited because of scarcity of archival specimens. We examined genotypes of pfcrt and dhfr in Indochina (Thailand, Myanmar, and Laos) and the Western Pacific (the Philippines, Indonesia, and Papua New Guinea) between 1984 and 1998 by testing samples obtained from malaria cases imported to Japan. Results show that 96% (28 of 29) and 77% (20 of 26) of samples had resistant genotypes of pfcrt and dhfr, respectively, substantiating the inferred history of clinical resistance in these geographic areas during this period.     

IgG4-related sclerosing cholangitis and autoimmune pancreatitis: histological assessment of biopsies from Vater's ampulla and the bile duct

Background and Aim: Autoimmune pancreatitis is commonly associated with immunoglobulin (Ig) G4‐related sclerosing cholangitis (IgG4‐SC). The discrimination between IgG4‐SC and pancreatobiliary malignancies or primary sclerosing cholangitis (PSC) is now an important issue. The present study was carried out to examine the usefulness of endoscopic biopsies from Vater's ampulla and the bile duct to diagnose IgG4‐SC. Methods: The present study included 29 IgG4‐SC patients (26 with both pancreatitis and cholangitis, and 3 with cholangitis only), 6 PSC patients, and 27 pancreatobiliary carcinoma patients. All patients underwent endoscopic biopsies from Vater's ampulla and the common bile duct. Biopsied specimens were histologically examined using immunostaining for IgG4. Results: For the ampullary and bile duct biopsies, the IgG4‐SC samples had a significantly greater number of IgG4‐positive plasma cells than the PSC or pancreatobiliary carcinoma specimens. In addition, bile duct biopsies from five patients (17%) with IgG4‐SC showed diffuse inflammatory cell infiltration with irregular fibrosis corresponding to the histological features of lymphoplasmacytic sclerosing pancreatocholangitis. Based on the threshold of 10 IgG4‐positive plasma cells per high power field, the diagnostic rates of the ampullar and bile duct biopsies were both 52% (15/29 cases). Twenty‐one patients (72%) had more than 10 IgG4‐positive plasma cells in at least one biopsy. The bile duct biopsy was significantly valuable for IgG4‐SC patients with swelling of the pancreatic head. Conclusion: The present study suggested that ampullar and bile duct biopsies are useful for diagnosing IgG4‐SC.     

Prevalence of germline GATA2 and SAMD9/9L variants in paediatric haematological disorders with monosomy 7

Monosomy 7 (−7) occurs in various types of paediatric myeloid disorders and has a poor prognosis. Recent studies have demonstrated that patients with germline gain-of-function SAMD9/9L variants and loss-of-function GATA2 variants are prone to developing myelodysplastic syndrome (MDS) associated with −7. However, the prevalence of the genetic variants among paediatric haematologic disorders with −7 is unknown. The present study screened germline variants of GATA2 and SAMD9/9L in 25 patients with various types of paediatric haematological disorders associated with −7. The diagnoses of the 25 patients included MDS (n = 10), acute myeloid leukaemia (AML) and myeloid sarcomas (n = 9), juvenile myelomonocytic leukaemia (n = 3) and other disorders (n = 3). Seven patients with a germline pathogenic GATA2 variant were found. For SAMD9/9L screening, next-generation sequencing was used to detect low-abundance variants and found four novel germline variants. Functional analysis revealed that three out of the four variants showed growth-restricting capacity in vitro and thus, were judged to be pathogenic. Cases with GATA2 mutation tended to be older, compared to those with SAMD9/9L mutations. In conclusion, GATA2 and SAMD9/9L were sequenced in 25 patients with paediatric haematologic disorders associated with −7, and 40% of them were found to have some pathogenic germline variants in the three genes.