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Subjective adverse reactions to metronidazole were analyzed in 111 patients with amebiasis. Metronidazole was administered to 36 patients at a daily dose of 2250 mg and 75 patients at daily doses lower than 2250 mg. The reactions reported included nausea without vomiting in 11 (9.9%) patients, nausea with vomiting in 2 (1.8%), dysgeusia in 2 (1.8%), diarrhea in 1 (0.9%), headache in 1 (0.9%), numbness in 1 (0.9%), dizziness in 1 (0.9%), urticaria in 1 (0.9%), exanthema in 1 (0.9%), and discomfort in 1 (0.9%). Nausea was reported by 28% (10/36) of the patients receiving metronidazole at a daily dose of 2250 mg and 4% (3/75) of the patients receiving lower daily doses. The duration of the metronidazole administration in days was not associated with the appearance of nausea. No life-threatening adverse reactions were identified, and good clinical therapeutic effects were observed in 96% (107/111) of the patients. While metronidazole appears to be a safe anti-protozoal agent for patients with amebiasis, our results indicate that a daily metronidazole dose of 2250 mg is excessive for amebiasis, as it often induces nausea.

With the increased survival of HIV-infected patients receiving antiretroviral therapy (ART), unexpected complications due to the untoward effect of antiretroviral agents or immunologic changes have been observed. Here, we report two cases of Graves' disease (GD) presenting with classic symptoms of hyperthyroidism occurring 44 and 47 months after ART initiation. Both patients had severe immune suppression prior to ART initiation (CD4 cell count≤50 cells/μL), with an increase on CD4 cell count to 354 and 329 cells/μL, respectively, at the time of GD diagnosis. Administration of methimazole (MMI) resulted in dramatic improvements in symptoms and thyroid function. In addition, CD4 cell count unexpectedly increased to500 cells/μL within three months on MMI. Hyperthyroidism caused by GD has been increasingly reported following the initiation of ART and may be related to immune reconstitution. The mechanisms underlying the increases in CD4 cell count after successful treatment of GD with MMI require further investigation, but may be due to improved immune recovery with the correction of hyperthyroidism or a specific effect of MMI on immune function.

Seismic reflection survey is the main technique for exploring the underground. While the position is not expected to change in the near future, the data quality in resolution and S/N ratio is always subject of improvement. The authors have developed the high resolution MEMS accelerometer for oil and natural gas exploration. In this research, the form of a MEMS element, size and electronic circuit were modified to enhance sensitivity of a prototype of MEMS to use in a MEMS accelerometer. The MEMS sensor made as an experiment by this research surpassed -130 dB/â??Hz which is the world highest ever by the performance evaluation test carried out. We are striving towards disseminating the developed MEMS sensors.

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.

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.

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.

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.

The effect of sparfloxacin (SPFX) on fecal microflora and its fecal concentrations were examined in four patients and one carrier with bacillary dysentery. SPEX was administered to five cases with a daily dose of 200 mg, once a day, for five days after breakfast. The results were as follows: Escherichia coli, a main bacterium in Enterobacteriaceae, was not detected during the drug administration, except one from whose feces mucoid type of E. coli was found all the time, and the colony forming units (CFUs) were not recovered to the initial level at the seventh day after the medication. Enterococcus, found in all of the cases before, was eliminated or decreased during and the CFUs showed slow recovery after the medication. Total CFUs of aerobes were decreased during and not returned to the initial level at the seventh day after the medication. Total CFUs of anaerobes were kept invariable, although variation of the CFUs with the species was seen. The peak levels of the fecal concentrations of SPEX were 177 to 535 micrograms/g on the third to the fifth day of the medication. The fecal concentrations were 1.3 to 4.4 micrograms/g at the seventh day after the medication in all of the cases. The clinical efficacy was excellent in three cases, poor in one evaluated for the other bacteria than Shigella, and unknown in one. No adverse reaction was observed.

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.

To the Editor: Enteric fever (typhoid and paratyphoid fever) is a systemic infection caused by several Salmonella enterica serotypes including S. Typhi and S. Paratyphi A. The Indian subcontinent, which has the highest incidence of the disease worldwide, is also an epicenter of enteric fever caused by multidrug-resistant (MDR; resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) and nalidixic acid–resistant (NAR) strains, i.e., strains with decreased susceptibility to ciprofloxacin (1–3). A total of 57% of S. Typhi strains isolated at a referral center in Dhaka, Bangladesh, in 2005 were MDR and NAR (4). More than 80% of 442 enteric fever cases reported in Japan during 2001–2004 were imported (5). Most Japanese persons, especially the younger generation, are not immune to enteric fever as are persons living in other industrialized countries. Although the proportion of enteric fever cases related to international travel has increased in industrialized countries, few outbreaks of enteric fever have been reported in travelers (6,7). We describe an outbreak of MDR and NAR typhoid fever in young Japanese travelers returning from Bangladesh. This outbreak highlights the need for standard treatments for MDR and NAR enteric fever. Ten Japanese junior and senior high school students living in the Tokyo metropolitan area took part in a 9-day study tour to Dhaka in March–April, 2004. They were escorted by 2 Japanese college students and a 28-year-old Japanese instructor. The 13 participants returned to Japan on April 4, 2004. The purpose of the study tour was to acquire knowledge about street children in Dhaka. The students stayed at a guesthouse and visited orphanages in the city. The itinerary included a visit to a local home, where the family served them a meal. They shared all their meals during the tour. Fever and diarrhea developed in 2 participants on April 3 and 5, and these symptoms were later shown to be caused by shigellosis. On April 19, the index patient became febrile. From that date until April 28, there were 6 confirmed and 2 probable typhoid fever cases reported in the 13 tour participants, resulting in an attack rate of 62%. The median age of the patients was 17 years (range 12–28 years); 5 patients were female. No other cases of typhoid fever were reported in that period in Japan. All 6 S. Typhi isolates were Vi-phage type E9. These isolates were also MDR and NAR, and the MIC for ciprofloxacin for the 6 isolates was 0.38 μg/mL. It was strongly suspected that a single-point exposure to S. Typhi occurred in the tour participants during their stay in Bangladesh and caused this exceptional outbreak. None of the participants had received a typhoid vaccination. The 8 patients were admitted to 5 hospitals in the Tokyo metropolitan area. Four different antimicrobial drug regimens were used on the basis of the age of the patients and the hospital in which each patient was hospitalized (Table). Four patients at 2 hospitals who received fluoroquinolone monotherapies were given other regimens on days 4–6 of treatment because of concern of treatment failure. The median fever clearance time was 6 days (range 3–12 days). No complications occurred during any of the treatment regimens. Although a relapse occurred 15 days after completion of treatment in the oldest patient, who had received cefotaxime and oral tosufloxacin, retreatment cured the infection without fecal carriage. Table Characteristics of 8 case-patients with typhoid fever, Bangladesh, 2004* The high attack rate may reflect the high sensitivity of adolescents to typhoid fever and the high level of bacterial contamination in food the participants had eaten during travel (2). Although the meal at the private home was suspected as the source of infection, we could not determine the exact cause of this outbreak. The optimum treatment for MDR and NAR enteric fever has not yet been established. A third-generation cephalosporin or high doses of fluoroquinolones (e.g., ciprofloxacin, 20 mg/kg/day or levofloxacin, 10 mg/kg/day) for 10–14 days are the drugs of choice (1,2). Azithromycin is also a promising agent (8). However, for any of the regimens, the mean fever clearance times are relatively long (≈7 days), and the relapse rates are high (1). Although all 6 isolates showed reduced susceptibility to ciprofloxacin, a long course (14 days) of fluoroquinolones was still effective in this outbreak. However, clinicians should be aware of treatment failure in MDR and NAR enteric fever (3). The combination therapy of cefotaxime and a fluoroquinolone used in 3 patients has not shown greater efficacy than monotherapies. In fact, 1 patient who received this combination therapy experienced a relapse.

Objective To study the adverse reactions and therapeutic effects of fluoroquinolones to investigate whether they can be used for the treatment of patients with typhoid fever and paratyphoid fever. Methods The adverse reactions and therapeutic effects of fluoroquinolones were studied retrospectively in patients with typhoid fever and paratyphoid fever. Patients 58 patients (54 Japanese) with typhoid fever, 42 patients (41 Japanese) with paratyphoid fever, and 1 Japanese patient with both typhoid fever and paratyphoid fever, who were admitted in hospitals in Tokyo, Kawasaki, Yokohama, Kyoto, and Osaka from 1995 to 1998 and treated with fluoroquinolones. Results Almost 80% of the patients were treated with tosufloxacin (TFLX) and the remaining 20 % were treated with norfloxacin, ciprofloxacin, levofloxacin, or sparofloxacin. Side effects (nausea, urticaria, aphthous stomatitis) and elevation of serum amylase were found in 3.6% and 8.3 % of patients treated with TFLX, respectively, but these adverse reactions disappeared in all of these cases either with or without a change in the drug used. No adverse reactions were found in patients treated with the other fluoroquinolones. The clinical and bacteriological effects of these drugs were adequate. Conclusion Though further studies still need to be performed on the fluoroquinolones other than TFLX, we can preliminarily conclude that fluoroquinolones are safe drugs and they can be recommended for the initial therapy of patients with typhoid fever and paratyphoid fever.

Portal hemodynamics were studied in 55 patients with hepatocellular carcinoma in comparison with 41 normal subjects, using the duplex system that consists of an electronic sector scanner and a pulsed Doppler velocitometer. Changes of portal hemodynamics after transcatheter hepatic artery embolization were also investigated in 15 of the patients with hepatocellular carcinoma. The duplex system showed that 9 of the 55 had no Doppler signal in the portal trunk, suggesting portal vein thrombosis, 2 had hepatofugal flow in the portal trunk indicative of arterioportal shunts, and 44 had hepatopetal flow in the portal trunk. One of the 9 patients with no significant portal venous flow showed hepatopetal flow in collateral veins at the porta hepatis, suggesting cavernous transformation of the portal vein. All of these ultrasound findings were confirmed by subsequent celiac-mesenteric angiography. In 44 of the 55 patients there was no tumor invasion in the portal trunk, and portal venous flow was found to be close to that of normal subjects regardless of the stage or size of tumor, and tumor invasion into relatively large portal branches. After transcatheter hepatic artery embolization, portal venous flow was increased, even on the next day, and it remained increased for at least 2 wk. Thus, the duplex system is useful to study qualitative and quantitative changes of portal hemodynamics in hepatocellular carcinoma. Our observations suggest that the portal venous flow is kept relatively constant by some homeostatic mechanism even in advanced hepatocellular carcinoma until the tumor invades into the portal trunk, and that it increases when hepatic arterial flow is occluded.

The results of a prospective randomized controlled trial of elective endoscopic intravariceal sclerotherapy carried out over a 36-mo period in comparison with elective percutaneous transhepatic obliteration of varices (PTO) are presented. Sixty-six patients with nonalcoholic cirrhosis were randomized after they had stabilized, usually between 7 and 14 days after variceal bleeding had stopped following medical treatment (balloon tamponade and vasopressin infusion). Thirty-three patients were assigned to the sclerotherapy group and the other 33 patients were assigned to the PTO group. The mean follow-up period was similar in both groups. There was no significant difference in demographic, clinical, and laboratory data between the two groups. Six patients (18%) in the sclerotherapy group and 21 (64%) in the PTO group had at least one episode of gastrointestinal bleeding during the follow-up period (p less than 0.005). Three patients in the sclerotherapy group and 1 patient in the PTO group bled from lesions other than varices; therefore the incidence of variceal bleeding was 9% in the former and 61% in the latter (p less than 0.005). The cumulative variceal bleeding rate was significantly lower in the sclerotherapy group than the PTO group (p less than 0.05). Five patients in the sclerotherapy group died during the follow-up period but none died of recurrent variceal bleeding. Nineteen patients in the PTO group died and 10 of them died of bleeding from varices. The cumulative survival rate was significantly better in the sclerotherapy group (p less than 0.05). These results indicate that elective endoscopic intravariceal sclerotherapy is superior to elective PTO in the prevention of recurrent variceal hemorrhage and mortality in nonalcoholic cirrhosis.

A 26-year-old woman Japanese public official servant in Lao People's Democratic Republic was introduced to our hospital on December 12, 2002, because of two months duration of low grade fever and severe eosinophilia. There was no significant finding in physical examination. Laboratory tests showed leukocytosis (15,700/microliter) with severe eosinophilia (42%), and no abnormal lymphocyte was observed. Furthermore, elevation in alkaline phosphatase (748 IU/l), gamma-glutamyl transpeptidase (190 IU/l), leucine aminopeptidase (150 IU/l), and slight elevation in CRP (2.8 mg/dl) were pointed out. A computed tomographic scan of the abdomen obtained multiple cystic lesions in the right lobe of the liver. On parasitological study, a stool specimen examined by the formalin-ether concentration method revealed positive for Opisthorchis viverrini eggs. She was orally administered with 40 mg/kg of praziquantel a day for two consecutive days. Following check-up by medical-affairs official at Embassy of Japan in Lao PDR confirmed the normal eosinophil count and her fever disappeared. It was considered eosinophilia in this case was induced by acute phase of severe ophisthorchiasis.