M Negishi

Tokyo Metropolitan Cancer and Infectious Diseases Center, Edo, Tōkyō, Japan

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Publications (32)22.44 Total impact

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    ABSTRACT: Emtricitabine (FTC) has been reported to cause skin pigmentation (SP), and the incidence of SP associated with FTC varied with ethnicity, with a higher rate in African-American patients (8%). We assessed the incidence of SP in Japanese HIV-1-infected patients receiving combination antiretroviral therapy (cART) with FTC for a period of 48 weeks and confirmed new findings of FTC-associated SP, including pathological characteristics. This was a multicenter, prospective, longitudinal non-randomized study. We evaluated the appearance of SP at 48 weeks as the primary endpoint in 155 Japanese patients, and secondary endpoints included the characteristics of the SP (location, color tone, size, and progression). Six cases (3.9%) of SP occurred at a median of 124 days (range: 7-259 days) within 48 weeks. The SP looked like an isolated dark spot, 1-2 mm in diameter, mainly on the hands and/or feet. The severity of all the SPs was mild. Each SP had disappeared or faded at a median of 112 days (range: 28-315 days) with continued FTC. FTC-associated SP was considered to be lentigo simplex by dermatoscopy and pathological appearance. In summary, the incidence of FTC-associated SP in Japanese patients was 3.9%, and was comparable to the previously reported incidence in Asian patients (4%). FTC-associated SP was not associated with any clinically significant symptoms and has little clinical significance.
    Journal of Infection and Chemotherapy 03/2011; 17(5):602-8. DOI:10.1007/s10156-011-0222-5 · 1.38 Impact Factor
  • Nippon Shokaki Geka Gakkai zasshi 01/2008; 41(1):135-140. DOI:10.5833/jjgs.41.135
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    Emerging infectious diseases 01/2008; 13(12):1954-5. DOI:10.3201/eid1312.070422 · 7.33 Impact Factor
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    Journal of Travel Medicine 09/2007; 14(5):343-5. DOI:10.1111/j.1708-8305.2007.00139.x · 1.53 Impact Factor
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    ABSTRACT: A 44-year-old woman referred for skin eruptions and an altered mental status was confirmed to have HIV infection on Western Blot analysis. Her CD4+ T cell count was 15/microl. On admission, she appeared quite ill with respiratory distress. Chest X-ray showed bilateral patchy infiltration and pleural effusions. She was treated with cefotaxime, pentamidine, and antituberculosis drugs, but her condition worsened and dopamine was initiated. Intensive treatment failed, and she died the following day. An autopsy showed purplish papules on her face and trunk and multiple white nodules in her liver, spleen and lungs. Culture was positive for Candida Albicans, yielding a diagnosis and of disseminated candidiasis. It is rare for HIV patients to be diagnosed with disseminated candidiasis, since the pathogenesis usually requires disruption of the mucosal barrier. The defense mechanism against disseminated candidiasis is mainly neutrophils and macrophages, and its dysfunction is not a primary characteristic of HIV infection. To the best of our knowledge, this is the first report in Japan of a HIV patient to have disseminated candidiasis.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 08/2007; 81(4):459-62. DOI:10.11150/kansenshogakuzasshi1970.81.459
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    ABSTRACT: A 45-year-old homosexual man with pneumocystis pneumonia and esophageal candidiasis tested positive in ELISA and Western blot analysis for HIV-1. His CD4+ T cell count was 43/microL and his HIV-RNA load was 250,000 copies/mL. He was treated with Trimetoprim-Sulfamethoxazole, Prednisolone and Fluconazole. Valganciclovir was added to treat CMV retinitis. During the clinical course, 21 days after admission, the patient presented with a temperature of 39 degrees C and blood analysis showed neutropenia. Cefepime and G-CSF were initiated, but new consolidation was observed in the upper left lobe in chest radiography. He underwent bronchoscopy and lavage culture was positive for Aspergillus fumigatus. Serum testing of galactomannan was also positive and pulmonary aspergillosis was diagnosed. The patient was initially treated with Micafungin but switched to Voriconazole when clinical symptoms worsened. An eventual clinical response was observed and pulmonary aspergillosis was controlled. Unfortunately, he died of sepsis due to MRSA 2 months later. Pulmonary aspergillosis is a devastating complication with poor prognosis in patients with HIV infection. Amphotericin-B has been the mainstay of pulmonary aspergillosis treatment, but reports indicate mortality exceeding 80%. Use of Voriconazole, a relatively new antifungal agent, may lower mortality with fewer adverse effects than conventional antifungal therapy.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 04/2007; 81(2):200-5. DOI:10.11150/kansenshogakuzasshi1970.81.200
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    ABSTRACT: To describe the clinical features of dengue cases in Japan, a retrospective study was conducted on 62 laboratory-confirmed Japanese dengue cases presented to Tokyo Metropolitan Komagome Hospital between 1985 and 2000. Age distribution was from 18 to 62 years old (mean, 31.5 years). All cases were imported from abroad and diagnosed as dengue fever. Clinical manifestations included fever (100%), headache (90%), and skin rash (82%). Laboratory examinations revealed leukocytopenia (71%), thrombocytopenia (57%), elevated levels of serum aspartate aminotransferase (78%), and lactate dehydrogenase (71%). Antibody responses were consistent with that of secondary flavivirus infection in 60% of cases. Severity of symptoms in patients with primary dengue antibody response and those with secondary flavivirus antibody responses didn't show statistical significance. Dengue virus infection should be taken into consideration in the differential diagnosis of febrile patients who recently entered Japan from tropical or subtropical countries.
    The American journal of tropical medicine and hygiene 10/2006; 75(3):470-4. · 2.74 Impact Factor
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    ABSTRACT: Recent introduction of highly active antiretroviral therapy (HAART) is reported to have reduced the incidence of lymphoma among HIV-infected individuals. A clinicopathological study was performed on 86 AIDS-related lymphoma patients who were treated in Tokyo area from 1987 to 2005. The incidence of lymphoma detected by autopsy was 27% (53 cases/198 autopsies). Diffuse large B cell lymphoma was the most predominant histological subtype throughout the period (78%). Burkitt's lymphoma (BL) increased from 2% in the pre-HAART era (before end-1997) to 13% in the HAART era, whereas incidence of BL did not vary between HAART users and non-users. Epstein-Barr virus (EBV)-positive lymphoma decreased from 88% in the pre-HAART era to 58% in the HAART era, but did not differ significantly between HAART users (73%) and non-users (74%). Nodal involvement of lymphoma increased from 14% in the pre-HAART era to 50% in the HAART era; however, central nervous system involvement decreased from 62 to 38%. Kaposi's sarcoma-associated herpesvirus infection was rare (4%) among all cases. These data suggest that HAART might play a partial role in these changes, and the alteration in immunological backgrounds, such as EBV prevalence, is suggested as another leading cause of these changes in Japanese AIDS-related lymphoma.
    Microbes and Infection 05/2006; 8(5):1301-7. DOI:10.1016/j.micinf.2005.12.012 · 2.73 Impact Factor
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    ABSTRACT: Four patients infected with Cyclospora cayetanensis who sought medical care at the Tokyo Metropolitan Komagome Hospital are herein presented. All were Japanese males, and their ages ranged from 22 to 50 years of age. One patient, who was HIV-positive with a CD4+ lymphocyte count of 141/microliter, demonstrated no AIDS-defining illness. This patient acquired HIV in some Southeast Asian country/countries through heterosexual contact. This patient presented with watery diarrhea with a frequency of up to 18 times a day for more than two months. The other three cases were not considered to be debilitated hosts. Diarrhea occurring from one to ten times a day continued for 6 to 26 days in all of these three patients. The presumed origin of the infection was considered to be Southeast Asian countries and the season of onset of diarrhea was March to July in all four cases. Treatment with a sulfamethoxazole/trimethoprim compound was performed for both the HIV-infected patient and the other non-debilitated patient. Both symptomatic and parasitologic improvements were quickly observed in these patients. A prospective study was performed using fecal specimens from the diarrheal patients to identify the presence of C. cayetanensis during the period from 1996 to 2001. Protozoa-positive specimens were found in 3 of 410 (0.7%) specimens from patients who had traveled overseas, is one of 148 (0.7%) for HIV-infected (the C. cayetanensis-positive patient also acquired the protozoa in Southeast Asia), and in none of 513 (0%) patients who developed diarrhea in Japan. In summary, C. cayetanensis infection is rare in Japan and most patients infected with this pathogen tend to be overseas travelers and HIV-infected individuals at present.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 07/2002; 76(6):416-24.
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    ABSTRACT: Two separate febrile Indian patients who reside in Japan and had recently returned from their country were diagnosed as suffering from typhoid fever. Fluoroquinolone therapy was clinically ineffective and the addition of a third-generation cephalosporin was required in each case. Each strain of Salmonella Typhi was resistant to nalidixic acid in vitro and also showed higher minimal inhibitory concentration to other quinolones than usual susceptible strains. Similar cases of typhoid fever responding poorly to quinolone treatment have been observed in the Indian subcontinent, south-east Asia and central Asia since the early 1990s, and potential spread by travelers into Japan is of serious concern. Although quinolones still remain the drugs of choice for treatment of typhoid fever, physicians should be aware of the possibility and implications of clinical treatment failure.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 02/2001; 75(1):48-52. DOI:10.11150/kansenshogakuzasshi1970.75.48
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    ABSTRACT: Patients with typhoid fever presenting to the Tokyo Metropolitan Komagome Hospital during the period 1975-1998 were retrospectively investigated. All cases were diagnosed by a positive culture for Salmonella typhi in either of their clinical specimens. Of the total number of 130 patients, 57% contracted the disease abroad; this population increased in later years as the total numbers of cases decreased. The period from disease onset to diagnosis averaged 14 days with 20% of the cases requiring over three weeks to establish a diagnosis. As for symptomatology relative bradycardia was seen in less than half of the cases, and rose spots or splenomegaly in less than one third. A positive blood culture was the most frequent test establishing the diagnosis followed by a positive stool culture. Intestinal bleeding was recognized in as many as 35 cases (27%) and even intestinal perforation occurred in two cases (1.5%). Chloramphenicol was most commonly employed during the early study period, however, during the late period it was replaced by fluoroquinolones. The clinical cure rate was 98% with regimens that include fluoroquinolones/quinolone; however it was 87% with the other antimicrobial regimens. Bacteriological relapse occurred in 25% of the non-fluoroquinolone group while only in 2.0% in the fluoroquinolone/quinolone group. Four strains of Salmonella typhi that were multi-resistant to chloramphenicol, ampicillin and cotrimoxazole were isolated in travelers from Asia. Early diagnosis by appropriate bacteriological examination regardless of classical symptomatology should be stressed and the use of fluoroquinolones is warranted in the treatment of typhoid fever.
    Microbiology and Immunology 02/2000; 44(7):577-83. DOI:10.1111/j.1348-0421.2000.tb02536.x · 1.31 Impact Factor
  • Japanese journal of infectious diseases 01/2000; 52(6):249-50. · 1.20 Impact Factor
  • Japanese journal of infectious diseases 07/1999; 52(3):131-2. · 1.20 Impact Factor
  • Parasitology International 08/1998; 47:199-199. DOI:10.1016/S1383-5769(98)80518-7 · 2.11 Impact Factor
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    ABSTRACT: Prulifloxacin (PUFX), a new quinolone antimicrobial agent, was administered to a total of 122 patients and carriers to investigate its clinical efficacy, safety and usefulness in infectious enteritis (bacillary dysentery, enteritis caused by Salmonella spp. and enteropathogenic E. coli, cholera and so on). In addition, the minimum inhibitory concentration (MIC) of UFX (active compound) was determined against each clinical isolate, and compared with that of ciprofloxacin (CPFX), ofloxacin (OFLX), tosufloxacin (TFLX) and nalidixic acid (NA). The correlation between the concentration of UFX in feces and the change of the fecal microflora were also investigated when PUFX was administered to the patients with acute infectious enteritis. A daily dose of 400 mg of PUFX was administered orally in two divided doses (morning and evening) for 5 days, with the exception of 7 days administration against salmonella enteritis and 3 days administration against cholera. 84 cases were adapted for evaluating the usefulness. The clinical efficacy was 100% in all the enteritis except salmonella enteritis, in which it was 88.9% (8/9 cases). On the bacteriological efficacy, the elimination rate was 100% in all isolates except Salmonella spp., in which it was 75.0% (12/16 cases). As for the adverse effect, uriticaria in moderate degree was observed in 1 (0.9%) of 109 cases. Abnormal changes in laboratory findings were seen in 3 (3.0%) of 100 cases, consisting of 1 with eosinophilia and 2 with elevated S-GPT, although they were all slight in degree. The usefulness rate was 65.5% (55/84 cases) for "very useful" and 95.2% (80/84 cases) for "very useful" and "useful". MIC90 of UFX against Shigella spp., Salmonella spp., E. coli and V. cholerae, was 0.025, 0.05, 0.025 and 0.05 microgram/ml, respectively. These values were the same as those of CPFX and TFLX, and superior to OFLX and NA. UFX concentrations in feces followed by administration of PUFX in 3 cases with acute infectious enteritis were higher than that of MIC90 of UFX against Shigella spp., Salmonella spp., E. coli and V. cholerae. The changes of the fecal microflora, which influence the efficacy and safety of PUFX, were not observed.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 08/1996; 70(7):727-45.
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    ABSTRACT: A clinical study was carried out on pazufloxacin (PZFX) in 137 patients including shigellosis, Salmonella enteritis, enteropathogenic Esherichia coli enteritis and cholera, and carriers of these pathogens. Antibacterial activity of PZFX against clinical isolates, fecal concentration of PZFX and effects of PZFX on fecal microflora were also investigated. The overall clinical efficacy rate was 97.2%. The bacteriological efficacy rates were 98.2% against Shigella spp., 81.8% against Salmonella spp., 50% against Vibrio cholerae O1, and 100% against E. coli, V. parahaemolyticus, Aeronomas spp., Plesionomas shigelloides and V. cholerae non-O1, respectively. Side effect (epigastralgia) was observed in 1 of 130 cases (0.8%). The rate of abnormal laboratory findings was 11.2% (11/98). These were mainly elevation of GOT and/or GPT and increased eosinophils. The clinical usefulness rate was 95.2%. The MIC90 values of PZFX against Shigella spp., Salmonella spp. and E. coli were 0.025, 0.025 and 0.025 micrograms/ml, respectively. The results of fecal drug concentration and the effects on fecal microflora in one patient were compatible with those obtained in healthy volunteers.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 02/1996; 70(1):60-72.
  • International Hepatology Communications 07/1995; 3. DOI:10.1016/0928-4346(95)90709-G
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    ABSTRACT: A clinical study was conducted on fleroxacin (FLRX) in 143 patients and carriers with infectious enteritis (shigellosis, Salmonella enteritis, Campylobacter enteritis, pathogenic Escherichia coli enteritis, Vibrio parahaemolyticus enteritis, cholera, multiple bacterial infections, pathogen-negative enteritis). Furthermore, its antibacterial activity against clinical isolates, fecal concentration and effect on fecal microflora were conducted. FLRX was administered orally in doses of 200 mg once a day (200 mg group) or 300 mg once a day (300 mg group) for 3 days to cholera, for 7 days to Salmonella enteritis and for 5 days to the other infectious enteritis. The clinical efficacy rates were 100% in both the 200 mg and 300 mg groups. The bacteriological efficacy rates were 100% against Shigella spp., Salmonella spp., pathogenic E. coli, V. parahaemolyticus and V. cholerae O1, and 63.6% against Campylobacter spp. in the 200 mg group. The rates of the 300 mg group were 93.3% against Shigella spp., and 100% against Campylobacter spp. and pathogenic E. coli. As adverse effects, skin rash was observed in 1 case each in both groups (1.1%, 2.1%). Abnormal laboratory findings consisted of 1 case of increased eosinophils and 1 case of elevated GOT and GPT levels in the 200 mg group (2.8%), and 1 case of elevated GPT in the 300 mg group (2.9%). The clinical usefulness rates were 92.9% and 93.3% in the 200 mg and 300 mg groups, respectively. Antibacterial activity was somewhat inferior to that fo ciprofloxacin and equal to or better than that of norfloxacin, demonstrating MIC90 values against Shigella spp., Salmonella spp., pathogenic E. coli, V. parahaemolyticus and Campylobacter spp. of 0.1, 0.2, 0.1, 0.2 and 0.78 micrograms/ml, respectively. Peak fecal concentrations of the drug were 49.0 micrograms/g and 274.4 micrograms/g in the 200 mg group, and 43.3 micrograms/g and below the detection limit (5.0 micrograms/g) in the 300 mg group. With respect to fecal microflora (4 cases), a decrease in Enterobacteriaceae was observed in 3 cases during dosing. But this change showed a tendency to recover after completion of dosing. No effects were observed on anaerobic bacteria.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 12/1994; 68(11):1390-408.
  • Atsushi Ajisawa · Masayoshi Negishi · Gouta Masuda · Tsuyoshi Yamaguchi
    Nippon Ishinkin Gakkai Zasshi 01/1994; 35(3):247-252. DOI:10.3314/jjmm.35.247
  • Nippon Ishinkin Gakkai Zasshi 01/1994; 35(3):253-255. DOI:10.3314/jjmm.35.253