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A 68-year-old female patient presented with advanced gastric cancer and multiple hepatic tumors. Upper GI endoscopy showed a type 3 lesion in the posterior wall of the gastric body. Abdominal computed tomography revealed multiple liver metastases, and staging laparoscopy identified peritoneal dissemination. She was diagnosed with clinical Stage Ⅳ gastric cancer(cT3N2M1H1). She received 3 courses of combined chemotherapy containing S-1 and cisplatin. The therapeutic response was PR. We performed total gastrectomy with D2 lymph node dissection and splenectomy. Histopathological examination revealed no residual cancer cells, indicating pCR. She continued S-1 adjuvant chemotherapy and has remained free from recurrence for 18 months.

Background: Immune reconstitution syndrome (IRS) is a complication caused by reactivation of the immune system that can occur after starting highly active antiretroviral therapy (HAART) in patients with acquired immunodeficiency syndrome (AIDS). Severe IRS associated with cytomegalovirus (CMV) in both eyes who had lost his left vision is reported., Case: A 37-year-old man with AIDS who had started HAART discontinued his medication. Two weeks after the re-induction of HAART, he suffered CMV retinitis OU. Vitreous opacity OU appeared 3 days later, and optic neuritis OS appeared 6 days after the onset; and visual acuity OS decreased to 0.06. As the number of CD 4 positive T lymphocytes (CD 4) increased from 39 to 118/microl in both the pre- and- post HAART, we diagnosed IRS and started anti- CMV and systemic steroid therapy and discontinued the HAART. The focus of CMV retinitis was improved; however, visual acuity OS did not improve., Conclusion: Severe IRS with visual loss induced by CMV retinitis after HAART needs to be considered in low CD 4 level patients during the induction phase.

More than 25 years have passed since HIV was identified as a causative agent of AIDS. In the monotherapy era, the efficacy of antiretroviral therapy was limited due to emergence of drug resistance. In late 1990s when the highly active antiretroviral therapy (HAART) was started to apply, the mortality of HIV infected people dramatically declined. Nowadays, more than 20 drugs are applicable and treatment regimen has become more potent and more convenient. However, emergence of multi-drug resistant HIV and long-term toxicity of antiretroviral is still remarkable concern. Raltegravir, the first approved integrase inhibitor (INI), shows preferable safety profile. When long-term reliability of INI is proven, antiretroviral combination will be individualized by choosing the optimal drug from 4 classes.

HIV infection is known as one of sexually transmitted infection and number of new HIV-infected patients is increasing in Japan. It' s still difficult to detect HIV-infected career because HIV career has no symptoms for several years after HIV infection. HIV treatment is progressing and made HIV-infection controllable disease, although HIV can not be eradicated from body. This therapy is needed life-long continuance because HIV can easily achieve mutation that decrease efficacy of antiretroviral drugs. Thus, we should perform HIV screening test more actively to prevent the further spread of infection and if detected, must educate importance of adherence of therapy.

We evaluated a novel anti-human immunodeficiency virus type-1/2 (HIV-1/2) antibody detection kit for detecting anti-HIV-1/2 antibodies in whole blood based on the counting immunoassay (CIA) using an automated immunochemical analyzer (PAMIA-40i). This kit to detected all antibodies tested including those against HIV-1 subtype A to F, B/D in group M, HIV-1 group O, and HIV-2, and captured antibodies 4 to 7 days earlier than immunochoromatocraphic tests in the commercial seroconversion panel. In this study using 70 HIV-seropositive patients and 90 HIV-seronegative healthy individuals, both sensitivity and specificity were 100%. This automatic system using CIA for whole blood can be completed within 15 min and examine many samples simultaneously. This system used latex-counting technology and reliably detects the low-titer antibodies in whole blood.

Background: Viral load quantification is standard for monitoring HIV-1 therapy and is crucial in deciding whether to switch or to continue a current antiretroviral regimen. In Japan, serum is widely adapted as a specimen of the HIV-1 viral load quantification assay., Methods: We evaluated an emerging HIV-1 RNA quantification of the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test (COBAS TaqMan). The test was evaluated for matrix equivalence between plasma and serum and for correlation with the AMPLICOR HIV-1 Monitor Test v1.5 (Amplicor) for HIV-1 RNA quantification., Results: The test result from serum specimens showed good correlation with test results from plasma specimens. HIV-1 RNA quantification results using serum specimens correlated well with those obtained by both ultrasensitivity assay and standard Amplicor assay., Conclusions: The fully automated COBAS AmpliPrep/COBAS TaqMan HIV-1 Test meets requirements for a wide dynamic range and reliable quantification of HIV-1 RNA in serum clinical specimens.

We report a 54-year-old Japanese man who contracted severe falciparum malaria after visiting West African countries. The patient presented with Plasmodium falciparum parasitemia of 10% on admission and was successfully treated with intravenous artesunate combined with continuous hemodiafiltration. We found that intravenous artesunate had excellent antimalarial activity with rapid parasite clearance and that few adverse effects were observed compared to those reported for intravenous quinine treatment. Supportive therapy was indispensable for saving the life of the patient. Few cases of intravenous artesunate treatment are reported in Japan because the drug has not been legally registered. We wish to emphasize the efficacy of intravenous artesunate with general supportive therapy in the treatment of possible imported severe malaria patients in Japanese medical settings.

Purpose: To evaluate the recent clinical manifestations of ocular complications in patients with human immunodeficiency virus(HIV) infection., Methods: We retrospectively reviewed the medical records of 94 new HIV-positive patients examined at the International Medical Center of Japan between April 1, 2002, and March 31, 2003, and listed the details of ocular complications. The use of highly active antiretroviral therapy (HAART) and CD 4 cell counts was also recorded in patients with cytomegalovirus (CMV) retinitis and iritis/vitritis., Results: The following ocular complications were recognized in 31 patients: retinal microvasculopathy (11 cases), CMV retinitis (10 cases), inactive inflammatory changes (6 cases), iritis/vitritis (5 cases), optic nerve atrophy (2 cases), papilledema (2 cases), ocular tuberculosis (1 case), progressive outer retinal necrosis (1 case) and conjunctival Kaposi's sarcoma (1 case). In patients with CMV retinitis, the CD 4 cell counts at the onset were lower than 50/microl except in 1 case. Iritis and/or vitritis were recognized in 5 cases, and the onset of 4 cases occurred after the beginning of HAART. Among the patients studied, immune recovery uveitis was suspected in 3 patients with a history of CMV retinitis., Conclusions: Ocular complications were recognized in almost one third of the patients in our series. Immune recovery uveitis was suspected in 3 patients with iritis/vitritis who previously had CMV retinitis.

A 33-year-old female who had been on a steroid treatment for the past 14 years due to systemic lupus erythematosus (SLE) visited our hospital complaining of mild headache. No neurological deficit and no positive serologic tests for lupus anticoagulants (LAC) and anticardiolipin antibodies (aCL) were noted. Only a mild inflammatory change was observed on routine hematological examination. On neuroradiological examination, MRI revealed thickened falx cerebri and tentorium cerebelli, and an empty delta sign. These findings were suggestive of sinus thrombosis of superior sagittal sinus (SSS). Angiograms clearly demonstrated occlusion of the posterior part of superior sagittal sinus and transeverse sinus (TS). Conservative treatment was chosen because of no evidence of intracranial hypertension. There was no deterioration in her general and neurological status during her hospital stay and she was discharged. Longstanding vasculitis and pachymeningitis related to lupus erythematosus might be the probable cause of the sinus thrombosis in this case.

Saquinavir (SQV) is a human immunodeficiency virus (HIV) specific protease inhibitor. When combined with ritonavir (RTV), plasma concentration of SQV is increased. In this study, we examined pharmacokinetics of SQV soft-gel capsule (SQV-SGC) 400 mg twice daily (BID) combined with RTV in HIV-1-infected patients (n = 4) and compared with those of SQV hard-gel capsule (SQV-HGC) 400 mg BID combined with RTV (n = 12). Pharmacokinetics of SQV-SGC 1,200 mg single dose in healthy subjects (n = 10) were also studied. Peak SQV concentration in plasma (Cmax) and area under the plasma concentration-time curve from 0 to 8 hour (AUC0-8 h) of SQV-SGC 400 mg BID combined with RTV group were higher than those of SQV-HGC 400 mg BID combined with RTV group; increase of 14.7% and 25.5%, respectively. Cmax and AUC0-8 h of SQV-SGC were higher than SQV-SGC 1,200 mg single dose group; increase of 3.9 fold and 8.5 fold, respectively. These results indicated that SQV-SGC combined with RTV therapy is the most potent antiviral effect among SQV-SGC with RTV, SQV-HGC with RTV, and SQV-SGC alone.

Spread of multi-drug resistant malaria in the endemic areas has made malaria control more difficult. Thus, WHO recommends combination therapy for the treatment of malaria. The aim of combination therapy is to improve efficacy and to reduce the incidence of resistance development to the each component of the combination. Particularly, the combination with artemisinin derivatives shows good outcome in Thailand where high resistance for mefloquine has already been found. We report the first case of falciparum malaria, successfully treated with Artemether-Lumefantrine in Japan. Artemether-Lumefantrine is a newly developed artemisinin-based combination agent for the treatment of uncomplicated multi-drug resistant malaria. This drug has proved highly effective and well tolerated by some clinical trials abroad. This Japanese female case showed a good clinical course without any side effect.

Introduction of HAART (highly active antiretroviral therapy) has resulted in dramatic reductions in AIDS-related opportunistic complications and death. We have faced, however, severe complications due to HAART such as lactic acidosis and lipodystrophy syndrome. Regimens currently employed in the treatment may be complex, require multiple drugs to take, difficult to tolerate owing to adverse effects, and decrease level of quality of life in some patients. Decisions about when and with what to initiate HAART must take into account the risk-benefit ratio associated with the therapy. In this article, issues that must be considered in determining timing of initiation and choice of anti-retroviral drugs are discussed.

Highly active anti-retroviral therapy(HAART) for human immunodeficiency virus(HIV) has delayed the disease progression. The advances prompted us to undertake liver transplantation in a 41-year-old man with hemophilia B, HIV infection, and hepatitis C(HCV) end-stage liver disease. The donor was the patient's elderly brother. His right liver was implanted by the standard method. Two months after the operation, interferon alfa and ribavirin were administered for HCV infection. HCV was eradicated two weeks after the treatment. The HIV viral load is persistently negative and HAART has not been started so far. Utilizing a organ from living relatives should be one of the options to resolve the concern around the utilization of a scarce public source from cadavers for patients who may not have an equivalent survival to HIV negative patients.

In order to investigate the long-term prognosis and clinical efficacy of highly active antiretroviral therapy (HAART) in HIV-1-infected hemophiliacs, we compared clinical courses of 69 HIV-1-infected hemophiliacs and 29 non-hemophiliacs all of whom were asymptomatic between 1990 and 1993. Changes of CD4 count during 1990 through 2000 in both groups were not significantly different. The time to death due to AIDS in both groups were also not significantly different. The major causes of death not related to AIDS in hemophiliacs were bleeding, liver cirrhosis, and liver cancer. A total of 55 (39 hemophiliacs and 16 non-hemophiliacs) out of 98 patients survived in 1997. Since then, the 28 hemophiliacs and the 12 non-hemophiliacs received HAART. Although the percentage of patients whose viral loads (VL) decreased to below undetectable level (VL < 400 copies/ml) by the initial HAART regimens without saquinavir were not significantly different, continuation of the same regimens in the hemophiliacs were significantly longer than non-hemophiliacs (84 weeks vs. 51 weeks, p < 0.05). From starting HAART to July 2000, 35.7% of the hemophiliacs were changed regimens three times or more. That is higher prevalence comparing with non-hemophiliacs of 16.7%. This study suggests that there might be the patient group who have to been changed HAART regimens frequently in the hemophiliacs.

HIV infection was first reported in 1981 in USA. It has been 20 years since then. Owing to understandings of pathogenesis of this disease and development of new drugs such as the HIV-specific protease inhibitor (PI), prognosis of disease has been tremendously improved. Especially after 1997 in Japan, the strategy of anti-HIV treatment shifted from two drugs combination to three drugs combination, which is called highly active antiretoviral therapy (HAART). HAART was so effective that prevalence of HIV associated opportunistic infections were decreased dramatically. Mortality among hospitalized HIV-infected patients was decreased from 6.7% in 1996 to 2.6% since then in ACC. However, 80% of patients receiving HAART suffered from side effects and 15% of them had to be changed their treatment due to side effects. Furthermore, an unexpected side effect, namely lipodystrophy syndrome (LDS), was emerged among patients who were receiving HAART more than one year. LDS was first reported as re-distribution of lipid such as central obesity with or without lipo-atrophy from extremities and/or face. Now only cosmetic change, but also it is associated with elevation of lipid and glucose level. Therefore, those patients who have LDS are in face of the risk for the ischemic heart diseases. Our survey indicated that the rate of LDS in Japanese patients were almost same as that of Caucasian patients reported elsewhere. Opportunistic infections associated with HIV infection Treatment for HIV infection consists of two major arms; one is use of anti-HIV drugs to prevent development of AIDS described above and the other is diagnosis, treatment, and prophylaxis of opportunistic infections. There are five very important opportunistic infections; Pneumocystis carinii pneumonia (PCP), cryptococcus meningitis, toxoplasma encephalitis, cytomegalovirus (CMV) infection, and Mycobacterium avium complex (MAC) bacteremia. Because if these five were able to diagnose, a patient can survive under appropriate treatment. On the other hand, if these were not diagnosed, patient must be AIDS death. After introducing HAART, number of CMV retinitis, MAC bacteremia, and AIDS dementia complex were decreasing. However, number of PCP sustained high because PCP is the first indicator disease of AIDS if the patient did not know his HIV status. The first choice of drug is sulfamethoxazole/trimethoprim (ST) for PCP treatment. If the patient were in severe respiratory failure, corticosteroid is used concomitantly. Treatment is usually continued for 3 weeks. We have successfully treated 45 out of 47 cases of PCP for 4 years. However, those patients treated with ST for 3 weeks were limited only 35% because of very high rate of side effects of ST. If the patient was intolerant to ST, treatment was switched to pentamidine. After finishing the treatment, the patient is to be treated with a 5-day course of oral desensitization to ST. More than 80% of patients who were previously intolerant to ST became successfully getting tolerance by this method.