Search

We herein report the case of a 25-year-old man who was referred to our hospital due to acute cytomegalovirus (CMV) colitis. The initial blood tests showed that the patient had concurrent primary human immunodeficiency virus (HIV) infection and severe thrombocytopenia. Raltegravir-based antiretroviral therapy (ART) was initiated without the use of ganciclovir or corticosteroids and resulted in a rapid clinical improvement. Platelet transfusions were only necessary for a short period, and subsequent colonoscopy revealed a completely healed ulcer. This case implies that ART alone could be effective for treating severe thrombocytopenia during primary HIV and CMV coinfection.

We present 3 cases of ocular syphilis in patients who had been newly diagnosed as having HIV. All the patients had only complained of ophthalmologic symptoms at the time of their initial visit. Treatment with penicillin was successful, resulting in no significant sequelae. Ocular syphilis may lead to reduced visual acuity or even blindness if left untreated. However, the diagnosis may be challenging, since patients may lack symptoms that are commonly observed in cases with primary and secondary syphilis. Considering the recent increase in the number of syphilis patients, clinicians should be aware of ocular syphilis and should have a high index of suspicion for syphilis in any patient at risk so as to ensure a prompt diagnosis.

Lung cancer has become a crucial problem among individuals living with the human immunodeficiency virus (HIV) and causes high mortality in Western countries. Japan has an increasing number of newly infected HIV patients, and lung cancer is becoming a theme in this population. However, clinical factors of this particular population in East Asian are unclear given the identification of ethnic differences in lung cancer in the general population.From 1986 to 2013, a retrospective nationwide study involving Japanese patients living with HIV and diagnosed with lung cancer was undertaken.Forty-three lung cancer patients with HIV were identified (median age, 60.0 years; males, 97.7%; early-stage cancer, 37.2%; metastatic cancer, 34.9%), 41 (95.3%) of whom developed lung cancer in the antiretroviral era. The median CD4-positive T-cell count was 326 cells/µL. Adenocarcinoma was the most frequent histology (55.8%), followed by squamous cell carcinoma (27.9%). Epidermal growth factor receptor (EGFR) status was examined in 14 patients; five (35.7%) had EGFR mutations. The median overall survival time was 25.1 months for all stages and 7.9 months for advanced-stage cancer. Using univariate analysis, the only favorable prognostic factor for overall survival was cancer stage (p = 0.02).The incidence of lung cancer among HIV patients in Japan has been increasing in the past decade. The present Japanese cohort showed similar EGFR mutation status similar to that of general population. The ethnic differences known in the general population were seen even in the population living with HIV, implying distinct clinical characteristics and outcomes from those reported in Western countries.

Objective: Acquired immunodeficiency syndrome-related non-Hodgkin lymphoma is treated similarly to non-acquired immunodeficiency syndrome lymphoma, but it is not clear whether highly intensive regimens are beneficial for acquired immunodeficiency syndrome-related Burkitt lymphoma. We conducted a multicenter retrospective survey to clarify the clinical outcomes of acquired immunodeficiency syndrome-related Burkitt lymphoma in the combined antiretroviral therapy era in Japan. Methods: We retrospectively analyzed the outcome of 33 patients with acquired immunodeficiency syndrome-related Burkitt lymphoma, who were diagnosed at five regional hospitals for human immunodeficiency virus/acquired immunodeficiency syndrome in Japan between January 2002 and December 2010. Results: The median follow-up period was 20.0 months (range 0.5–92.7 months). Six (18.2%) patients were treated with cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate, ifosphamide, etoposide and high-dose cytarabine, and 23 (69.7%) patients were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, high-dose methotrexate and high-dose cytarabine. The overall response rate for all patients was 78.8%, with a complete response rate of 72.7%. The two-year overall survival rate was 68.1%. There was no significant difference in overall survival between chemotherapeutic regimens with rituximab (n ¼ 20) and without rituximab (n ¼ 13) (P ¼ 0.49). The two-year overall survival rate was 66.7% for patients receiving cyclophosphamide, vincristine, doxorubicin, dexamethasone, etoposide, ifosfamide and cytarabine, and was 72.6% for patients receiving cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and cytarabine (P ¼ 0.72). There was one treatment-related death. Conclusions: Highly intensive chemotherapy would bring a high remission rate and prolonged overall survival for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma.

A 19-year-old Filipino man was admitted to our hospital because of persisting fever and back pain. He had recognized his symptoms 6 months previously, but a definite diagnosis was not made. Image testing demonstrated a compressed fracture of the thoracic vertebrae accompanied with a perivertebral abscess. A biopsy specimen revealed granuloma compatible with tuberculosis (TB). Anti-TB drugs were initiated, and his clinical symptoms steadily improved. However, he developed neuropathic symptoms due to exacerbation of the abscess two months after starting the anti-TB drugs. An immediate laminectomy was performed resulting in symptom relief; however severe kyphosis remained. Polymerase chain reaction testing of the abscess collected during the operation was positive for Mycobacterium tuberculosis, confirming the diagnosis of spinal TB. The diagnosis of spinal TB has been a challenge world-wide. Clinicians should be aware of the demographic background as well as the clinical and laboratory features of spinal tuberculosis, facilitating earlier diagnosis.

We report herein on a 20-year-old Japanese man who was referred to our hospital for fever and diarrhea after returning from Indonesia. On admission, his blood test was essentially normal, besides a slight elevation in inflammatory markers. After excluding malaria and dengue fever, empiric use of ceftriaxone was initiated for suspected enteric fever, which was unsuccessful. However, drastic clinical improvement was observed after initiation of minocycline. The polymerase chain reaction test for Rickettsia typhi was positive from serum samples on admission, confirming the diagnosis of murine typhus. Although rarely seen in Japan, clinicians should be aware of this disease when examining patients with fever coming back from murine typhus endemic areas.

We report on a previously healthy 56-year-old woman who was referred to our hospital with fever and progressive left foot pain. She had been bitten by a cat 7 days previously, and cephalosporins had been prescribed for treatment. However, her clinical symptoms deteriorated, and physical examination on admission was compatible with necrotizing fasciitis. Treatment with ampicillin-sulbactam and clindamycin was initiated. In addition, immediate surgical debridement was performed, resulting in therapeutic success. Culture of the necrotizing tissue grew multiple organisms, including Pasteurella multocida and Bacteroides caccae. Administration of appropriate antibiotics after a cat bite is essential for the prevention of potentially fatal complications.

We describe herein two cases of sick sinus syndrome possibly due to lopinavir-ritonavir in HIV-infected individuals. The heart rate dropped to 30 to 40 beats per minute in both cases, but patients remained asymptomatic and recovered promptly after discontinuation of lopinavir-ritonavir. The time until onset varied; one patient developed bradyarrhythmia 9 days after the initial dose, and another 4 hours after. Since lopinavir-ritonavir is a frequently used antiretroviral agent, clinicians must be aware of this potentially lethal adverse effect.

We herein report a 52-year-old man infected with human immunodeficiency virus (HIV) who was referred to our hospital due to the development of severe neurocognitive disorders and bilateral leukoencephalopathy. He has been treated with antiretroviral agents for 17 years, but low-level viremia has been detected consistently prior to admission. Drug resistant testing of the serum and the cerebrospinal fluid (CSF) both demonstrated a M184V mutation. A brain biopsy revealed perivascular CD8(+) T-lymphocyte infiltration, leading to the diagnosis of CD8 encephalitis. The clinical symptoms improved drastically after changing to a nucleoside reverse transcriptase inhibitor sparing regimen, which subsequently decreased the HIV viral load to an undetectable level in both the serum and CSF.

Background: The number of HIV-infected patients who require palliative or end-of-life care is increasing, and the status of end-of-life care for HIV patients with malignancies is unclear. Aim: This study aimed to evaluate the end-of-life care provided to HIV patients with malignancies in Japan. Design: National cross-sectional questionnaire-based survey. Setting/participants: Questionnaires were delivered to the medical staff of 378 regional core hospitals/core hospitals for AIDS and 285 palliative care units in Japan. Data were collected between August and October 2013. Results: Overall, 226 regional core hospitals/core hospitals for AIDS (59.8%) responded. A total of 55 institutions (24.3%) provided end-of-life care to HIV patients with malignancies. Regarding the place of death of the patients, 69.1% died at the institution whereas 18.2% were transferred to palliative care units. The requests of 16 (29.1%) institutions to transfer patients to palliative care units were rejected. Of the 378 palliative care units, 179 (62.8%) responded. While 13 palliative care units (4.6%) provided care to hospitalized HIV patients with malignancies, 20 (11.2%) refused to accept these patients for treatment because of a lack of experience in treating these patients and a lack of knowledge regarding HIV infection. Conclusion: Our findings suggest that in Japan, HIV patients with malignancies have difficulties obtaining hospitalization at a palliative care unit, which is likely due to a lack of experience among the professionals in treating such patients as well as a lack of knowledge about HIV.

We report a case of a 45-year-old Japanese man with AIDS-associated Kaposi's sarcoma (KS) involving skin, liver, and lungs. Antiretroviral therapy was started in conjunction with pegylated liposomal doxorubicin (PLD). A clinical response was observed initially, but symptoms recurred following cessation of medication. The chemotherapeutic agent was changed to paclitaxel (PTX), since the therapeutic response to PLD was reduced and the total dose reached the maximum dose of 500 mg/m2. The patient had a good response to PTX and tolerated the medication well. Symptoms did not recur after completing 8 courses of chemotherapy. PTX should be considered as an alternative agent in treating KS when there are problems with the use of PLD.

We report on a 26-year-old Japanese man who was referred to our hospital because of anal pain and hematochezia. On admission, in addition to his gastrointestinal symptoms, a generalized maculopapular rash was observed, involving the palms of his hands and soles of his feet. His history and physical examination were compatible with syphilis, confirmed by a high syphilis titer on blood examination. Further tests revealed the presence of HIV infection, with a CD4 cell count of 227/microL. Colonoscopy demonstrated a deep ulcer in the lower rectum, although biopsy specimens did not reveal any syphilis spirochetes, or any other specific microorganisms. Intravenous penicillin G was initiated, resulting in a dramatic improvement of the ulcers along with the skin lesions confirming the diagnosis of syphilis proctitis. A rapid plasma reagin titer test performed 3 months after treatment demonstrated significant decrease, indicating successful treatment.

Lung cancer has emerged as a crucial problem among human immunodeficiency virus (HIV)-infected patients, contributing to significant mortality in Western countries. Japan has an increasing number of newly infected HIV patients, but clinical characteristics of lung cancer have not been well investigated in Asian populations with HIV. We retrospectively analyzed patients diagnosed with HIV and lung cancer simultaneously in our institution between 1985 and 2010. Data regarding HIV status, characteristics, treatment, and prognosis of lung cancer were evaluated. We identified 13 consecutive patients (all men; mean age, 59.0 ± 10.2 years) since 1985, 7 of whom had been diagnosed since 2008. Mean CD4 cell count was 332 ± 159 cells/μL, and HIV viral loads were undetectable in 8 patients (61.5%) at the time of lung cancer diagnosis. The mean latency from HIV diagnosis to detection of lung cancer was 4.0 years. Histological examination demonstrated adenocarcinoma in 9 patients (69.2%), followed by squamous cell carcinoma (23.1%), and small cell carcinoma (7.7%). Among the 7 patients available for examination, 2 patients (28.6%) harbored EGFR mutation. Six patients had stage IA–IIIA, and 7 patients had stage IIIB/IV. Among 6 patients treated with chemotherapy for unresectable stages, 5 (83.3%) achieved a partial response. Median overall survival was 17 months for all stages and 14 months for advanced stages. Toxicities for treatment modalities were largely acceptable. Clinical characteristics of Japanese HIV-infected patients with lung cancer resemble those of Western populations. The prognosis for patients in the metastatic stage was better than previously reported.

We report a case of pathologically confirmed malignant syphilis in an HIV-infected patient. Physical examinations revealed ulceronecrotic skin lesions. Skin biopsies demonstrated syphilis spirochetes on immunohistochemical stain, and syphilis serological titers were positive. Treatment with intravenous penicillin G was begun, and complete resolution of the skin lesions was observed. A rapid plasma reagin titer test performed 3 months after treatment revealed a 4-fold reduction in the titer, indicating successful treatment.

Primary central nervous system lymphoma (PCNSL) related to acquired immunodeficiency syndrome (AIDS) is a lethal disorder, but the recent application of highly active antiretroviral therapy (HAART) has significantly improved prognosis. This retrospective cohort study of AIDS-related PCNSL examined the actual clinical outcomes and prognostic variables affecting overall survival (OS) in the HAART era. Twenty-three newly diagnosed AIDS-related PCNSL at 12 regional centre hospitals for HIV/AIDS in Japan between 2002 and 2008 were consecutively enrolled. The estimated 3-yr OS rate of the entire cohort was 64% (95%CI, 41.0-80.3%). Whole brain radiation therapy (WBRT) had an independent positive impact on survival (WBRT >or=30 Gy vs. others, P = 0.02). Nine of 10 patients with a good performance status (PS) (0-2) remained alive with complete response, whereas 10 (77%) of 13 of those with a poor PS (3-4) died mostly after a short period. The estimated 3-yr OS rate of the groups with a good and poor PS was 100% and 38% (95%CI, 14-63%), respectively (P = 0.01). Leukoencephalopathy (grade >or= 2) developed in 21% of those that survived more than 12 months after radiation. The patients receiving a curative intent radiation dose (>or=30 Gy) of WBRT achieved prolonged survival while maintaining a good quality of life in the HAART era, especially among patients with a favourable PS.

Kidney disease is a significant cause of morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). However, epidemiologic and clinical variables regarding kidney disease have not been determined among HIV-infected patients in Japan.A cross-sectional study of 788 HIV-infected outpatients including 706 men was conducted in 2009. The patient's mean age and CD4+ T cell count were 46.2 +/-11.8 years and 418 +/- 202/microL, respectively. Of them, 677 patients (86%) had an undetectable HIV-RNA level (50 copies/mL). Random urine and blood samples were collected to study the coexistence of chronic kidney disease (CKD). In addition, serum cystatin C was measured since it is considered to be an alternative marker of early kidney dysfunction in the HIV population. The estimated glomerular filtration rate (eGFR) based on serum creatinine was calculated using the 3-variable equation, proposed by the Japanese Society of Nephrology [eGFR (mL/ min/1.73m2) = 194 x Serum creatinine (-1.094) x Age (-0.287 x 0.739 (if female)]. CKD stages were classified based on the National Kidney Foundation guidelines.The prevalence of CKD and that of CKDor = stage 3 was 14.9% and 9.4%, respectively. The pro-portion of each stage was as follows: stage 1, 15 patients (1.9%); stage 2, 28 patients (3.6%); stage 3, 66 patients (8.4%); stage 4, 1 patient (0.1%); stage 5, 1 patient (0.1%); and stage 5D, 6 patients (0.8%). Elevation of serum cystatin C (or = 0.9 mg/L) was found in 23.3%. Comorbidities such as hypertension and diabetes were found in 55.4% and 27.0% in patients with CKDor = stage 3, respectively. Urinalysis showed 71 patients (9.1%) with proteinuria and 44 patients (5.6%) with hematuria.CKD has become an important comorbidity for HIV-infected patients in Japan, a point that should be given more emphasis from public health perspective.

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.

BACKGROUND HIV-associated neurocognitive disorders (HAND) have emerged as a problem among HIV-infected individuals in the era of antiretroviral therapy. However, there are insufficient data on HAND regarding its prevalence and clinical features in Japan. METHODS A test battery composed of eight neuropsycological tests proposed by the Ministry of Health, Labour and Welfare (MHLW test battery) was applied to assess 30 subjects at Tokyo Metropolitan Komagome Hospital. Among them, 5 subjects were excluded due to central nervous system complications. The background of each patient along with the results of head magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis and neuropsychological tests were compared to each HAND category. In addition, the clinical utility of a combination of neuropsychological tests as an abbreviated test battery of HAND was evaluated. RESULTS A total of 19 (76%) subjects were diagnosed as having a HAND. Among them, HIV-associated dementia, mild neurocognitive disorders and asymptomatic neurocognitive disorders were diagnosed in 7, 8, and 4 subjects, respectively. Neither the patient's background nor the results of the head MRI and CSF analysis showed relevance to disease severity. The conventional International HIV Dementia Scale with the Digit Symbol Substitute Test was capable of detecting 94.7% cases of HAND. CONCLUSIONS Most HIV-infected subjects clinically suspected as having neurocognitive disorders were diagnosed as having a HAND. Neuropsychological tests of the MHLW test battery were in some part useful to diagnose HAND. However, more precise neuropsychological tests are warranted to screen and diagnose HAND, based on the current criteria.

Varicella has been thought to be one of the representative infectious disease in childhood, but recently we are under the impression that adults contracting varicella are increasing in number. On the other hand, they say that varicella generally causes a serious illness in adult patients. So we investigated signs and symptoms of varicella, source of infection, occupations of adult patients, except those who were immunologically compromised, by means of medical records, to know the characteristics of varicella in adulthood. According to the varicella severity score proposed by Nagai et al., varicella in the hospitalized adult patient was found to be much severer than that in children. The most remarkable symptoms, were high fever and sore throat, and these were the main reason of hospitalization in most of our patients. Although severity scores were very high in admitted adult patients with varicella, their clinical courses were not serious, and most of them recovered with only supportive therapy. These patients rarely suffered from complications, like pneumonia. If adult patients with varicella hospitalized in the early stage and received supportive care, they could recover without any complications. In most cases of adult varicella the source of infection was unknown. In the case of married persons, however, many of them were infected through their child. When adults contract varicella, not only the patients themselves suffer from high fever and sore throat, but also they act as the source of infection, if they are medical care workers. Furthermore, in public, the contraction of varicella results a socioeconomic loss from suspension of business caused by the illness. Prophylaxis with varicella vaccine, therefore, should be considered, when there are people who have never contracted varicella, whether or not they are medical staff.

BACKGROUND In 2012, the number of rubella cases sharply increased in Japan. It continued to rise in 2013. Between October 2012 and May 2013, 10 cases of congenital rubella syndrome (CRS) were reported nationwide. This current rubella outbreak comprised mainly males who were between 20 to 39 years of age, and had not received the rubella vaccine. Data have been lacking on the clinical characteristics of adults infected with the rubella virus. METHODS Using medical charts, we collected data from 27 patients who were diagnosed with clinically or laboratory-confirmed rubella infection at Tokyo Metropolitan Komagome Hospital from January 2012 to April 2013. RESULTS Of the 27 patients studied, their median age was 34.5 years and 70.4% were male between 21-56 years of age. For the 11 cases with known vaccination status, 9 (81.8%) occurred in persons who had not received a rubella vaccine. A total of 33.3% of the patients were hospitalized, due to persistent fever, poor oral intake, or dehydration. Major clinical symptoms were fever (96.3% of cases), lymphadenopathy (92.6%), rash (85.2%), conjunctivitis (77.8%), and headache (63.0%). The mean duration of fever was 5 days (range, 3-9). The exanthema consisted of punctate, pink maculopapules; however, the rash became confluent in 37.0%, and pigmented in 18.5% of the patients. Initial laboratory data were as follows:white cells, 3,800/microL (range: 2,000-8,300); platelets, 129,000/microL (range, 63,000 - 230,000); aspartate aminotransferase, 27IU/L (range, 16 - 49); lactase dehydrogenase, 279IU/L (range, 168-440) [all described in medians]. Rubella-specific immunoglobulin M antibodies from the serum sample obtained at the initial visit were detected in 17 cases (65.4%). Likewise, measles-specific immunoglobulin M antibodies were detected in 7 cases (26.9%), all of which were false-positive. CONCLUSIONS The clinical characteristics of rubella in adults resembled measles in some part, which may cause difficulty for physicians to differentiate between the two diseases. Vaccinating rubella-susceptible individuals now is critical to interrupt rubella virus transmission, and to prevent further CRS cases.

The improved survival of subjects with human immunodeficiency virus (HIV) has been accompanied by an increased prevalence of chronic kidney disease (CKD). Epidemic of CKD among those with HIV has not yet been evaluated in multiple tertiary hospitals in Japan.A cross-sectional study was conducted in 2011 at Tokyo Metropolitan Komagome Hospital (TMKH) and Tokyo Medical University Hospital (TMUH). A total of 1482 HIV-infected subjects (1384 men, 98 female, mean age: 44.2 +/- 11.4 years old) were consecutively enrolled in the study. Random urine and blood samples were collected to study prevalence of CKD. CKD was diagnosed as a decrease in glomerular function and/or proteinuria and classified into 5 stages based on National Kidney Foundation guidelines. The estimated glomerular filtration rate based on serum creatinine was calculated using the 3-variable equation, constructed by the Japanese Society of Nephrology. Proteinuria was defined asor = 1+ on urine dipstick examination. All electronic medical charts were reviewed to determine comorbidities, including hypertension and diabetes mellitus (DM). The proportion of subjects receiving tenofovir disoproxil fumarate (TDF) was investigated. Risk factors for CKD were determined using multivariate logistic regression analysis.The mean CD4 cell count was 487 +/- 216/microL and 80.5% had undetectable HIV-RNA level in the combined cohort. Of the 90.2% of subjects taking antiretroviral agents, 61.5% was using TDF. The prevalence of overall CKD and CKDor = stage 3 was 12.9% and 6.7%, respectively, both of which were nearly 3-fold higher in the TMKH cohort (p.0001). Mean age and proportional prevalent hypertension and DM were significantly higher in the TKMH cohort than in the TMUH cohort. Multivariate analysis showed significant CKD to be associated with ageor =50 years (odds ratio [OR], 2.81), hypertension (OR, 3.04), and DM (OR, 2.05).CKD prevalence was 12.9% among combined cohorts, but differed significantly between them. Differences in age distribution and the proportion of comorbidities, including hypertension and DM, are likely involved.

The case of a 66-year-old woman with untreated diabetes mellitus who was admitted to our hospital with a fever, hypotension and an altered mental status is herein reported. Computed tomography revealed bilateral emphysematous pyelonephritis along with a splenic abscess. Blood and urine cultures grew Escherichia coli. Treatment with systemic antibiotics combined with the insertion of percutaneous and renoureteral catheters was successful. The patient was discharged and completed treatment without developing any subsequent complications.

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.

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.

The efficacy, safety and usefulness of balofloxacin (BLFX) for patients with acute infectious enteritis and the carriers mainly shigellosis, were investigated. The drug was administered at a daily dose of 200 mg twice a day for 3 days to patients with cholera, 7 days to patients with Salmonella enteritis and 5 days to patients with other conditions of infectious enteritis including shigellosis; 1. The efficacy was analyzed in 89 of the 135 patients who received the administration (43 patients with shigellosis, 14 with Salmonella enteritis, 8 with enteropathogenic/ enterotoxigenic Escherichia coli enteritis, 3 with cholera, 7 with enteritis with other pathogenic bacteria, 6 with polymicrobial infectious enteritis and 8 with acute enteritis that was pathogen-negative). 2. In patients bearing symptoms and who thus could be analyzed for drug efficacy, the drug was markedly effective or effective 50/52 (96.2%). 3. Bacteriologically, the drug was effective for Shigella spp. in 41 (100%) of 41, Salmonella spp. in 12 (85.7%) of 14, and enteropathogenic/enterotoxigenic Escherichia coli in 8 of 8 cases. 4. Adverse effects were seen in 5/133 patients (3.8%) receiving the drug, including two cases of skin eruption, one of the numbness of the hands, one of oral aphtha, and one of nausea. In patients for whom laboratory findings were available, 20/115 (17.4%) showed abnormalities, mainly elevations of GOT and/or GPT, but these were slight. 5. In terms of subjective reports of usefulness, 51/82 (62.2%) were markedly satisfied, and 73/82 (89.0%) were either satisfied or markedly satisfied. 6. The influence of administration of BLFX on fecal concentration and intestinal microbial flora was investigated in 2 patients with acute infectious enteritis. Results approximately equivalent to such flora levels in healthy subjects were obtained. These results suggest that BLFX is highly useful for infectious enteritis such as that caused by shigellosis.

To determine whether there is a significant association between human immunodeficiency virus (HIV)-related retinal microangiopathy and systemic cytomegalovirus (CMV) disease in HIV-infected patients. Participants in this single-center, cross-sectional, retrospective study were 383 HIV-infected patients assessed for ocular manifestations before the beginning of antiretroviral therapy. The presence of HIV-related retinal microangiopathy, the presence of systemic CMV disease, laboratory data, and demographic information were determined by referring to medical records. The significance of any association between HIV-related retinal microangiopathy and systemic CMV disease was determined by use of the Chi-squared test and by multivariate analysis. HIV-related retinal microangiopathy was present in 85 patients, and was significantly associated with systemic CMV disease both by use of the Chi-squared test (P = 0.006) and by multivariate analysis (P = 0.045, odds ratio 2.03, 95 % confidence interval 1.02–4.06 adjusted for CD4+ cell count and plasma HIV-RNA level). These findings indicate that microangiopathy may be involved in the development of CMV disease in HIV-infected patients. Thus, detection of the presence of HIV-related retinal microangiopathy is important in the management of HIV-infected patients.

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.

Objective. To evaluate the usefulness of one of IGRAs, QuantiFERON-TB Gold (QFT-G), in human immunodeficiency virus- (HIV- ) infected patients with variousCD4+T cell counts.Methods. The QFT-G assay was performed using QFT-G kits among 107 HIV-infected patients including 9 cases with active tuberculosis (TB).Results. In HIV-infected patients withCD4+>50/μL, QFT-G positive rate for active TB patients was 5/6 (sensitivity=83%), and that for those without active disease was 1/69 (specificity=99%). The frequency of indeterminate QFT-G test was significantly higher in those withCD4+less than50/μL(P<.0001). At the same time there was a proportional relationship betweenCD4+and interferon-gamma response to mitogen (positive control) in QFT-G test (P=.0001).Conclusions. Our data suggested that QFT-G had high sensitivity and specificity in HIV-infected populations withCD4+greater than50/μL. However, QFT-G did not perform well in HIV-positive patients withCD4+less than50/μL.

Background: Kidney disease has become an important cause of morbidity and mortality in HIV-infected patients in Western countries. Japan is a country with an increasing number of newly infected HIV patients. However, only a few studies have investigated kidney disease in Asian populations infected with HIV. Methods: We studied the prevalence of kidney disease by reviewing the clinical data of 732 HIV-infected Japanese patients. Risk factors for proteinuria, albuminuria, and renal dysfunction were determined using multivariate logistic regression analysis. Results: Microalbuminuria, macroalbuminuria and proteinuria were present in 13.2, 4.55 and 9.52% of patients, respectively. The prevalence of chronic kidney disease of any stage and CKD ≧ stage 3 was 15.4 and 9.70%, respectively. Multivariate analysis showed significant associations between increasing levels of serum creatinine and cholesterol, and the coexistence of diabetes, hypertension and hepatitis C coinfection with either proteinuria or albuminuria, which was significantly related to the presence of renal dysfunction. Lower CD4 cell count was associated with the presence of renal dysfunction, but higher HIV-RNA level was not. Conclusions: Our study has shown the international dimension of the burden of kidney disease in HIV-infected patients. Either proteinuria or albuminuria is likely the most significant factor for renal dysfunction in these patients.

A child born from a mother with HIV infection was reported. We have followed the patient from 3 month old of age. Her HIV antibody disappeared at 7 month by EIA, and at 10 month by WR. But we confirmed her HIV infection by PCR and HIV culture, repeatedly at those times, PCR and HIV culture are thought to be necessary for sero-negative infants born from mothers positive for HIV antibody.

We studied clinical manifestations, laboratory results, treatment, recurrence, and complications in 69 patients diagnosed with Kikuchi's disease by lymph node pathology from January 1, 1998, to December 31, 2007. Subjects were 34 men and 35 women (median age: 28 years, range: 12 to 58 years). Of the 69, 67 were Japanese and 2 were Korean. Major clinical symptoms and signs were fever >37 degrees (71%) and lymphadenopathy (100%). Lymphadenopathy was cervical in 93% and systemic in 3%. Some experienced night sweats and weight loss. The median white blood cell count was 3800 microL (1,700-9,300 microl), and 50.7% of subjects had leukocytopenia (

The clinical efficacy, safety and usefulness of Rokitamycin (RKM), a new macrolide antibiotic, were compared with those of Ofloxacin (OFLX) for the treatment of Campylobacter enteritis by a double blind method. The daily dose level of RKM or OFLX was 600 mg. They were orally administered in three divided doses for 5 days. Of 223 cases studied, 106 cases were diagnosed as Campylobacter enteritis. Ninety cases (RKM group: 50, OFLX group: 40) except for 16 excluded or drop-out cases were analysed. There was no significant difference between the two groups in any background factors. The effectiveness and usefulness was evaluated in 88 cases (RKM group: 48, OFLX group: 40). The results obtained were as follows: 1. In a total of 82 strains of Campylobacter jejuni/coli (RKM group: 42, OFLX group: 40), the bacteriological efficacy rate of RKM (95.2%) was superior to that of OFLX (70.0%) with a significant difference (p = 0.006). 2. In 76 symptomatic patients (RKM group: 42, OFLX group: 34) on the day of the beginning of drug administration, the clinical efficacy rate was 97.6% in the RKM group and 85.3% in the OFLX group with no significant difference between the two groups. 3. In 88 evaluable patients, the global clinical efficacy rate of RKM (95.8%) was superior to that of OFLX (67.5%) with a significant difference (p = 0.001). 4. Side effect was observed in 1 (1.9%) of the 54 patients in the RKM group and none of the 44 patients in the OFLX group. Slightly abnormal laboratory findings were seen in 4 (10.8%) of the 37 patients treated with RKM and 3 (9.7%) of the 31 patients treated with OFLX, but there was no significant difference between the two groups. 5. In 88 evaluable patients, the clinical usefulness of RKM (91.7%) was superior to that of OFLX (67.5%) with a significant difference (p = 0.01). From these results, RKM is considered to be a very useful agent for the treatment of Campylobacter enteritis.

Case I: A middle-age homosexual male developed AIDS with Pneumocystis carinii pneumonia (PCP) and esophageal candidiasis in 1986 during his stay in an European country about five months prior to transfer to Tokyo Metropolitan Komagome Hospital, Tokyo, in 1987. He was also diagnosed as having cryptosporidiosis presenting with mild diarrhea a month following the diagnosis of PCP. Diarrhea was successfully treated with spiramycin. On transfer to Tokyo Metropolitan Komagome Hospital, he was febrile but had no diarrhea. Serum HIV and TPHA were positive and his blood lymphocyte subset T4a was markedly decreased. On the 13th day after transfer to the hospital, watery diarrhea appeared. Cryptosporidium oocysts were detected from the feces taken on the 17th hospital day. The patient died of Escherichia coli septicemia on the 38th hospital day. Autopsy finding yielded Cryptosporidium infection widely spread over the stomach, ileum, bile and pancreatic ducts. Case II: A 31-year-old previously healthy female presented with abrupt onset of mucous stool five times daily. Mucous passage continued on the subsequent days despite administration of loperamide, and the passage increased to 20 times daily with mucous to watery diarrhea associated with mild abdominal cramps and nausea on the 4th day after onset of illness. On the 6th day of illness, she visited Tokyo Metropolitan Komagome Hospital. She denied close contact with pet animals or contact with any person presenting diarrhea. She had no recent history of travelling anywhere outside Tokyo. On examination she was an apparently healthy woman except for a slightly distended abdomen with localized tenderness in the right upper quadrant.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.