[A case of acute pneumonia with prolonged false-positive results using an influenza test kit].

Influenza (flu) is a prominent infectious disease that worsens the general prognosis of older adults. We herein report a case of a clinically odd and rare reaction on an instant diagnostic kit for influenza. An 81-year-old man with a fever and rhinorrhea consulted our hospital. He had a history of dementia of Alzheimer's type and rheumatoid arthritis and had been treated with oral prednisolone (10 mg/day). Instant diagnostic test kit A using exudation from the upper pharynx showed positivity for antigen of flu A virus, and computed tomography indicated acute pneumonia. Immediately after the diagnosis, 150 mg/day of oseltamivir was started for 5 days. However, a high fever over 38.0°C persisted, and flu A antigen from the upper pharynx was repeatedly detected using test kit A. Despite subsequent oral treatment with 100 mg/day of amantadine and single venous infusion of 300 mg/day of peramivir, the high fever continued, and the detection of C-reactive protein in the serum as well as flu A antigen in the upper pharynx persisted. We suspected test failure, and the results of another test kit (kit B) were indeed negative. Furthermore, polymerase chain reaction performed by two independent laboratories failed to detect flu gene fragments. We concluded that the patient did not have the flu, and results of test kit A had been a false positive. The patient was successfully treated with ABPC/SBT infusions. We should consider the implications of diagnosing flu using instant test kits.

Key diagnostic characteristics of fever of unknown origin in Japanese patients: a prospective multicentre study.

OBJECTIVE: To identify the key diagnostic features and causes of fever of unknown origin (FUO) in Japanese patients. DESIGN: Multicentre prospective study. SETTING: Sixteen hospitals affiliated with the Japanese Society of Hospital General Medicine, covering the East and West regions of Japan. PARTICIPANTS: Patient aged ≥20 years diagnosed with classic FUO (axillary temperature≥38.0°C at least twice within a 3-week period, cause unknown after three outpatient visits or 3 days of hospitalisation). A total of 141 cases met the criteria and were recruited from January 2016 to December 2017. INTERVENTION: Japanese standard diagnostic examinations. OUTCOME MEASURES: Data collected include usual biochemical blood tests, inflammatory markers (erythrocyte sedimentation rate (ESR), C reactive (CRP) protein level, procalcitonin level), imaging results, autopsy findings (if performed) and final diagnosis. RESULTS: The most frequent age group was 65-79 years old (mean: 58.6±9.1 years). The most frequent cause of FUO was non-infectious inflammatory disease. After a 6-month follow-up period, 21.3% of cases remained undiagnosed. The types of diseases causing FUO were significantly correlated with age and prognosis. Between patients with and without a final diagnosis, there was no difference in CRP level between patients with and without a final diagnosis (p=0.121). A significant difference in diagnosis of a causative disease was found between patients who did or did not receive an ESR test (p=0.041). Of the 35 patients with an abnormal ESR value, 28 (80%) had causative disease identified. CONCLUSIONS: Age may be a key factor in the differential diagnosis of FUO; the ESR test may be of value in the FUO evaluation process. These results may provide clinicians with insight into the management of FUO to allow adequate treatment according to the cause of the disease.

Bibliographical investigation of complementary alternative medicines for osteoarthritis and rheumatoid arthritis.

BACKGROUND: A variety of complementary and alternative medicine (CAM) treatments are provided to the elderly. We investigated the efficacy and safety of CAM substances that are available to patients with osteoarthritis (OA) and rheumatoid arthritis (RA), both in Japan and overseas. METHODS: Information on CAM products was collected from the World Wide Web, using the keywords "arthritis" and "supplement" in five languages (Japanese, English, French, Italian and German) using a popular search engine for each of the languages. References to published work on the products were researched using PubMed with the keywords of "arthritis", "anti-inflammatory" and "analgesics". Such published work was classified according to the evidence levels established by the Cochrane Library. RESULTS: Two-hundred and sixty CAM products for OA or RA were available in Japan, of which 41 CAM products had been tested in randomized controlled trials (RCT); there was no scientific evidence for the remaining 219 CAM products. Most of the previous RCT suggested that CAM was effective in OA or RA. Herein, we confirmed the significant OA relieving effects of chondroitin sulfate through a meta-analysis. Effectiveness was assessed using subjective scores, not disease-specific immunological or serological markers for assessment. Toxicological investigations had only been performed for a few CAM products. CONCLUSION: Some CAM products that are effective against RA may be used together with biological therapy. However, some of the CAM products available in Japan should be tested using objective markers. Some CAM products for OA could be used for the relief of pain.

Effects of olopatadine in limited scleroderma with peripheral eosinophils.

Scleroderma and eosinophilia often occur together, though the pathogenesis is unclear. We investigated the effect of olopatadine hydrochloride in a series of cases of limited scleroderma (LS). Ten patients with LS and positive eosinophil counts (LSE) were enrolled (average age, 85 years; six men and four women). Serum concentrations of the anti-Scl-70 antibody were positive. Olopatadine hydrochloride was prescribed at 10 mg/day for 3 weeks. Serum concentrations of the anti-Scl-70 antibody significantly decreased, but changes in eosinophil numbers and percentages in peripheral blood were not significant. Factor analysis suggested a correlation between serum concentrations of the anti-Scl-70 antibody and complement C4. Olopatadine could be effective in reducing anti-Scl-70 antibodies in the elderly with LSE.

[CD5- CD11c+ CD23- small lymphocytic lymphoma evolving from aplastic anemia].

A 91-year-old woman was hospitalized with acute respiratory distress syndrome due to pneumonia in June 1997. Since she had pancytopenia and a bone marrow aspirate indicated hypocellularity with no increase in myeloblasts, dysplasia or abnormal chromosomes, aplastic anemia (AA) was diagnosed. Pulse therapy with methylprednisolone and antibiotics proved successful, and blood cell numbers stabilized. In June 2001, she was readmitted to our hospital with persistent low grade fever and leukopenia. A bone marrow aspirate from the sternum and iliac bone biopsy revealed compact proliferation of small lymphocytes, and the surface marker CD5- CD10- CD11c+ CD19+ CD20+ CD23- was detected through immune staining and flowcytometry. CD30+, CD34+and CD56+cells were scarce. Tests for surface immunoglobulins, IgG, IgA, IgM and IgD, were negative. No nodal or extranodal lesions were evident. Since Southern blot analysis of bone marrow cells indicated rearrangement of the immunoglobulin heavy chain and abnormal chromosomes were evident, small lymphocytic lymphoma (SLL) was diagnosed. Four intravenous infusions of rituximab (375mg/m2) were administered without critical adverse effects. Tests conducted four weeks later revealed saturation of CD20+ antigens of lymphoma cells and chromosomal abnormalities and rearrangement of the immunoglobulin heavy chain were still apparent. Though complete remission of the pancytopenia was not achieved, serum concentrations of lactate dehydrogenase and soluble interleukin-2 receptor decreased, and the numbers of platelets and erythrocytes increased. There was also an improvement in systemic condition. This was a rare case of SLL having the surface marker of CD5- CD10- CD11c+ CD19+ CD20+ CD23-, which had evolved from AA and infiltrated bone marrow.

Histopathological investigation of salivary glands in the asymptomatic elderly.

The significance of labial gland biopsies (LGBs) in the diagnosis of Sjögren's syndrome (SS) in the elderly has been a controversial subject since it is complicated by age-related histopathological changes. In an attempt to clarify the appropriateness of LGBs in present diagnosis criteria, we evaluated the specificity of LGBs using autopsied tissues. This was done by taking labial, sublingual and submandibular salivary glands from 53 autopsy subjects (24 males and 29 females) with an average age of 84 years, and testing them histopathologically with reference to a previously reported grading system. None had any sicca symptoms (oral dryness or dry eye). In subjects up to 75 years old, acinar atrophy was more frequent in labial glands than in the two major salivary glands (P=0.0098 for sublingual and P=0.0009 for submandibular glands). Also, while there were significant differences in frequency of such atrophy between the sublingual and submandibular salivary glands of subjects younger and older than 75, the labial glands showed no such variation. Taking grade 3 (focus score of 1) as the diagnosis criterion, two subjects were determined to have SS in which case the specificity was 95%. Using contemporaneous serological test results for anti-SSA/Ro antibodies as a diagnostic criterion raised specificity to 98%. For both major and minor glands, these appeared to be no relationship between degree of lymphocytic infiltration and age. Our results thus suggest that it is appropriate to adopt a focus score of 1 as a diagnostic criterion for SS in the elderly, and that serological test results can improve specificity.

[Clinical significance of soluble interleukin-2 receptor as a putative systemic nutritional index in the elderly].

The clinical significance of a slight increase of serum soluble interleukin-2 receptor (sIL2R) concentration in the stable elderly was investigated. Thirty-five residents of nursing homes with physical impairment as a sequel to cerebral infarctions, without any inflammatory condition, anodyne or immunological treatment, were divided into two groups: 24 without overt or suspected malignancy (NC) and 11 with a history of malignancy (CA). Serological screening with measurement of sIL2 R concentrations was performed and numbers of lymphocytes with CD4, CD8 markers were determined. The NC group was divided into controls (n = 15, sIL2R < = 883 U/mL) and subjects demonstrating elevation (n = 9, NH), as in a previous study. Differences were found in serum concentrations of albumin, blood urea nitrogen, total cholesterol concentration, Pettigrew's prognostic nutritional index (PNI), as well as the ADL score, but not age or sex between NH and controls. Factor analysis in NC revealed serum creatinine and blood urea nitrogen concentrations to correlate positively, and serum albumin, total cholesterol concentrations, ADL score, PNI to correlate negatively to sIL2R. Differences were found in sIL2R, albumin, total protein, total cholesterol, beta-lipoprotein, PNI between CA and controls, but correlations were not found in CA. Survival rate of controls over twenty-four months was better than that of NH, but not of CA. Our results suggest that a slight increase of concentration of sIL2R is related to subclinical systemic deterioration, especially with regard to nutrition, with a plausible connection to prognosis of the stable elderly without malignancy.

[A case of multiple myeloma with infiltration into skeletal muscle after injections of a granulocyte-colony stimulating-factor].

Multiple myelomas often occur in elderly people with complications due to aging. A 54-year-old man was first admitted with cerebral infarction, and multiple myeloma (IgG kappa, stage IIIA) occurred in November 1989 that was followed by partial remission after chemotherapy. The karyotype of the bone marrow cells was 46, XY, and no p53 gene mutations were detected by polymerase chain reaction and single-strand conformation polymorphism analysis. Chemotherapy (melphalan 10 mg, vindesine 3 mg, ranimustine 150 mg, prednisolone 60 mg for 4 days) was performed in February 1999 because of aggravation of the myeloma. After daily subcutaneous injection of 50 micrograms of nartograstim for six days to treat neutropenia, soft tissues around the right eye were swelled gradually without redness, accompanied by elevation of the serum creatine-kinase concentration. The swelling disappeared, and the enzyme level normalized after discontinuation of nartograstim. In July, on the sixth day of daily subcutaneous injection of 75 micrograms of filgrastim after the same chemotherapy, similar swelling of the soft tissues around the left eye became evident, and again this proved reversible. In July 2000, 40 mg of dexamethasone was infused, and after 5-day subcutaneous-injection of 75 micrograms of filgrastim daily, the right subclavicular soft tissue became swollen. He died of myocardial infarction, and autopsy revealed infiltration of myeloma cells into the right subclavicular muscle and bone marrow packed with myeloma cells. This case suggests that myeloma cells can proliferate and infiltrate into soft tissues on exposure to granulocyte-colony stimulating factors.