[Clinical study on ivermectin against 125 strongyloidiasis patients].

We treated 125 patients with strongyloidiasis (78 males and 47 females) by 2 oral doses of ivermectin (6 mg) at 2-week interval, and obtained the following results: 1. Eradication rate after treatment was 86.4% (108 of 125 patients), responsively. Out of the total 17 patients were resistant (non-responsive) to treatment, 8 patients received a further course of ivermectin and all Strongyloides stercoralis in their feces were eradicated. 2. Side effects were observed in 7.2% of the patients after the first dose treatment and in 3.2% after the second dose. But all symptoms were mild and self-limited. Although liver disfunction developed in 13.6% of the patients, no symptoms occurred and no special treatment was required. 3. Positive rate of anti-HTLV-I antibody in the resistant group was significantly higher (80.0%) than in the eradicated group (29.2%) and in the stool-negative group (0%). 4. Although eosinophils before treatment in the eradicated group was significantly higher than that of controls, there was no significant difference between the resistant group and controls. IgE levels in the resistant group was significantly lower than in the eradicated group. We would like to conclude that IVM is the best drug for treatment of the patient with Strongyloides stercoralis not only from this results but also our previous reports which had investigated the clinical efficacy on thiabendazole, mebendazole and albendazole.

[Clinical study on symptoms in patients with strongyloidiasis].

We treated strongyloidiasis patients and obtained the following results: Of the 299 patients (184 males and 115 females), 81 patients (27.1%) had no complaints before treatment, 218 patients complaints of some symptoms, including arthralgia and/or lumbago (28.4%), abdominal pain and/or borborygmus (19.3%), numbness of extremities (18.1%), constipation (16.3%) and itching (15.7). We treated 219 patients with mebendazole and symptoms improved after treatment described below: Thirty-seven of the 63 patients (58.7%) with arthralgia and/or lumbago improved. Twenty-seven of the 36 patients (75.0%) with numbness of extremities improved. Thirty-one of the 32 patients (96.9%) with heartburn improved. We treated 26 patients with mebendazole plus thiabendazole and twelve of 14 patients (85.7%) with abdominal pain and/or borborygmus were improved after treatment. We treated 54 patients with ivermectin and five of 18 patients (27.8%) with arthralgia and/or lumbago were improved after treatment.

[Clinical study of albendazole therapy for strongyloidiasis].

We reported the efficacy of albendazole (ABZ) for the treatment of 27 patients with strongyloidiasis. Twenty-seven patients, 23 males and 4 females, received 200 mg of ABZ one hour before breakfast and supper for 3 days and this treatment was repeated 2 weeks later. The following results were obtained: 1) The eradication rate at 2 weeks after the initial treatment was 70.4% (19 of 27 patients) and 2 weeks after the second course was 66.7% (16 of 24 patients). 2) One patients (3.7%) complained of abdominal pain after the first treatment. Four patients (14.8%) complained of headache (n = 2), nausea (n = 1) and exanthema (n = 1) after the second treatment. But all symptoms were mild and required no treatment and subsided in a few days. 3) Positive rate of HTLV-1 antibody was 45.8% in the patients. As described above, side effects occurred in some cases, although they were mild and transient. From these results, it can be concluded that on increased dose of ABZ could be much more favorable for the treatment of strongyloidiasis.

[Clinical study of eradicated and resistant patients to treatment with ivermectin for strongyloidiasis].

We treated 70 patients with strongyloidiasis (41 males and 29 females) with ivermectin (IVM), and obtained the following results: 1. The eradication rates at 1-2 months, 3-4 months and 5-6 months after treatment were 90.7% (49 of 54 patients), 100.0% (47 of 47 patients) and 95.7% (45 of 47 patients), responsively. Twelve patients were resistant (non-responsive) to treatment. 2. When compared to patients whose parasites were completely eradicated, the resistant patients showed the following results: 1) Incidence of symptoms observed before treatment was significantly lower (50.0% vs. 84.5%). 2) Positive rate of anti-HTLV-I antibody was significantly higher (66.7% vs. 20.7%). 3) Blood eosinophil counts before treatment were significantly lower (266.6 +/- 117.2/mm3 vs. 533.2 +/- 429.7/mm3). 4) Serum IgE levels before treatment were significantly lower (217.2 +/- 442.9 IU/ml vs. 1,076.8 +/- 2,108.0 IU/ml). 5) There were no significant differences in age, sex and dosage of ivermectin. 3. Comparing anti-HTLV-I antibody positive and negative patients, the following results were obtained: 1) Eradicated patients; a) Eosinophils and IgE levels before and after the first administration of medicine in anti-HTLV-I antibody positive patients were significantly lower than those of negative patients. b) Gammaglobulin levels before treatment and after both administrations of the drug, IgG before therapy and OKT4/OKT8 after therapy were significantly higher than in anti-HTLV-I antibody positive patients. 2) Resistant patients; Eosinophils after treatment were significantly lower in anti-HTLV-I antibody negative patients than in positive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Hereditary angioedema: a case with ascites yet no symptoms in the family.

An interesting case of hereditary angioedema in a 26-year-old female is reported, with a finding of transient effusion of fluid into the peritoneal cavity during the attacks. The patient suffered from recurrent abdominal pain for several years, but no family members had any similar symptoms. In spite of repeated hospital admissions and many examinations, accurate diagnosis was not made until the most recent admission. The recognition of hereditary angioedema as a cause of acute and/or recurrent abdominal pain may avoid useless invasive procedures and lead to adequate treatment in other similar cases.

Efficacy of ivermectin against Strongyloides stercoralis in humans.

Okinawa Prefecture is an endemic area of Strongyloides stercoralis infection. Since treatment of this infection remains unsatisfactory, we evaluated the efficacy of ivermectin. Twenty-three patients were treated with a single oral dose of ivermectin (mean +/- SD, 105.5 +/- 20.8 mcg/kg of body weight), followed by a second dose two weeks later. The rate of cure was 85.7% at 2 weeks after the first treatment, and 90.5% at 2 weeks after the second treatment. Side effects occurred in 2 patients (8.7%), but they were mild and transient. The results indicate that ivermectin might be useful and relatively safe for the therapy of Strongyloides stercoralis infection as an alternative to thiabendazole or mebendazole.

[Long term eradication rate of mebendazole therapy for strongyloidiasis].

We treated 245 strongyloidiasis patients with 7 schedules of mebendazole (MBZ) and obtained the eradication rates at 8 months to 2 years after the final treatment as described follows; MBZ (100 mg) was given twice a day orally. [Square bracket shows incidence of liver disfunction.] 1) The eradication rates at 2 years after single course of MBZ therapy for 28 days and a combination therapy (thiabendazole 500 mg powder form three times daily for 5 days followed by MBZ in powder form for 9 days, repeated once) were 93.8% (15 of 16 patients), [71.4%] and 100.0% (16/16), [50.0%]. 2) The eradication rates at 8-15 months after using MBZ alone in varying dosages were as follows: a) MBZ powder was administered for 5 days and was then repeated 1, 3 and 4 weeks later: 87.1 (27/31), [51.1%]. b) MBZ powder was given for 5 days and repeated 1 and 3 weeks later: 100.0% (7/7), [30.8%]. c) MBZ powder was administered for 4 days and repeated 1, 3 and 4 weeks later: 96.3% (26/27), [57.8%]. d) MBZ in tablet form was given for 4 days and repeated 1, 3 and 4 weeks later: 89.6% (43/48). [66.2%]. e) MBZ in tablet form was administered for 4 days and repeated 1 week later: 69.2% (9/13), [25.0%]. As described above, although the incidence of liver disfunction in the 4-day with 2-course therapy was lower than the other schedules, the eradication rate was lower. From these results, MBZ should be given to strongylodiasis patient for 4 days and repeated once, or for 3 days and repeated two or three times with 1 to 2 weeks intervals.

Cytotoxicity of mebendazole against established cell lines from the human, rat, and mouse liver.

The direct cytotoxicity of mebendazole (MBZ) was investigated by using cell lines derived from human, mouse and rat liver. It was demonstrated that Chang liver cells (derived from human liver) were more sensitive to the cytotoxic effects of MBZ than the other two cell lines. Longer incubation of the cells with MBZ resulted in stronger toxicity, and the cytotoxicity was dependent on the MBZ concentration above a certain threshold value (0.25-0.50 mg/l in a 42-h culture). Inhibition of the proliferation of Chang liver cells by MBZ was detected at a concentration of 0.008 mg/l, a lower concentration than that having a cytotoxic effect. The other two cell lines were less sensitive to the inhibitory effect of MBZ. Proliferation of human mononuclear cells following stimulation by phytohemagglutinin (PHA) was inhibited by MBZ, and this inhibition was more extensive than that of cells stimulated with whole formalin-treated Pseudomonas aeruginosa. It is suggested that dividing cells may be more sensitive to MBZ cytotoxicity. This anti-proliferative effect may be related to its clinically known side effects, such as hepatotoxicity and bone marrow suppression.

[Clinical study on ivermectin against Strongyloides stercoralis].

We previously reported the efficacy of ivermectin (IVM) for the treatment of 23 strongyloidiasis patients. We now reported the efficacy and safety of IVM therapy on 54 patients. Fifty-four patients, 28 males and 26 females, received a single oral dose of IVM one hour before breakfast and this treatment was repeated 2 weeks later. The following results were obtained: 1) The cure rate at 2 weeks after the initial treatment was 92.5% (49 of 53 patients) and 2 weeks after the second course was 96.0% (48 of 50 patients). 2) Four patients (7.4%) complained of diarrhea (n = 2 patients), constipation (n = 1), borborygmus (n = 1), dizziness (n = 1), diplopia (n = 1) and peri-anal itching (n = 1) after the first treatment. Three patients (5.6%) complained of borborygmus (n = 1), itching (n = 1) and exanthema (n = 1) after the second treatment. But all symptoms were mild and required no treatment and subsided in a few days. 3) Positive rate of HTLV-1 antibody was 25.9% in the patients. As described above, although side effects occurred in some cases, they were mild and transient. From these results, we concluded that IVM is an effective drug for strongyloidiasis.

[Comparison of efficacy of powder and tablet of mebendazole in the treatment of strongyloidiasis].

We previously treated 47 patients with 100 mg of mebendazole (MBZ) twice a day by oral use for 5 days and this treatment was repeated 1, 3 and 4 weeks later. Although the cure rate was 100%, liver injury was observed in 48.9% of the patients. On this study, we reduced the periods of administration of MBZ (powder; 100 mg twice a day) to 4 days, and repeated it once after 3 days interval, and this initial treatment was performed one more time after 10 days interval (group 1). As Strongyloides stercoralis is mainly located in upper digestive systems, we used the drug reduced to powder for the purpose of better contact with the parasites. We considered that the powder should be absorbed well and liver injury occurred in high incidence. As group 2, we used the tablet itself in the same schedules of group 1. The results obtained were as follows; 1) The eradication rates at 10 days after the initial treatment were 97.8% (44 of 45 patients) in group 1 (powder) and 93.0% (40/43) in group 2 (tablet). 2) At 3 days after the whole treatment, the eradication rates were 100.0% in group 1, and 97.7% (42/43) in group 2. 3) Slight side effects such as constipation (6.7% in the group 1), dizziness or vertigo (6.7% in the group 1) and itching (6.7% in the group 2) were observed. 4) Liver injury was observed at 11.1% (5/45) 10 days after the initial treatment in the group 1 and 13.3% (6/45) in the group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of strongyloidiasis with mebendazole--long-term eradication and new trials].

We previously reported the short period cure rate of mebendazole (MBZ) treatment to strongyloidiasis. We are now reporting the long period cure rate of the treatment. The results were as follows: 1) The cure rate was 73.9% (17/23) in single use of MBZ (100 mg twice daily for 28 days). 2) The cure rate was 100.0% (22/22) in combination therapy (thiabendazole 500 mg three times a day for 5 days and after that, MBZ 100 mg twice daily for 9 days). Before we obtained the cure rate of 6 months after the treatment described above, we concluded that MBZ could be used for the treatment of strongyloides infection because of the lack of severe side effects and suitable intervals between courses would prevent liver injury. Thus, in this study, 47 patients were treated with 100 mg of MBZ twice a day for 5 days and this treatment was repeated 1, 3 and 4 weeks later on the same schedules (group 1). But because of liver injury, 13 patients were interrupted and moved to the 4th course (group 2). The following results were obtained: 1) Out of a total of 60 patients, the cure rate was 88.1% (52/59) after 2 courses, 92.3% (12/13) after 3 courses and 100.0% (46/46) after the 4 courses were finished. 2) Diarrhea (10.6%), arthralgia and lumbago (8.5%) were observed in group 1. No side effects were observed in group 2. 3) The incidence of liver injury occurred 48.9% (23/47) in group 1 and 30.8% (4/13) in group 2. 4) Positive rate of HTLV-I antibody was 40.0% (24/60).(ABSTRACT TRUNCATED AT 250 WORDS)

[New trial with thiabendazole for treatment of human strongyloidiasis].

Okinawa prefecture is well known as an endemic area of Strongyloides stercoralis infection, and its recent infection rate was reported 6.2%, which was investigated by a new technique to detect S. stercoralis, agar plate method. Traditional treatment with thiabendazole was temporarily effective for S. stercoralis, but the recurrence rate was extremely high. We tried the new treatment for the purpose of complete eradication of the parasite. The patients were divided into two groups, who were given 500 mg of thiabendazole three times daily for 5 days and not medicated for the following 9 days. The medication was repeated 3 times in group 1 which consisted of 92 patients and 4 times in group 2 which consisted of 70 patients. Obtained results were as follows: 1) Six months after treatment, the cure rate was 89.5% in the only one course treatment, and 100% in more than 2 course treatments. 2) Side effects such as nausea, vomiting, anorexia or general fatigue were noted in 67.5% of all the patients after initial treatment, and 45.1% of the patients were dropped out of this trial. The dose of the drug was reduced in 32.1% of the patients, and only 22.8% were treated with full course of the regimen. 3) The elevation of S-GPT was observed in 33.8% of all patients. After initial treatment the rate was only 8.1%, but after 3 or 4 repeated course of treatments the rate was elevated to 39.0% and 45.4%, respectively. The liver injury was closely related to the total dose of thiabendazole and the period of the medication.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of strongyloidiasis with mebendazole and its combination with thiabendazole].

Although Strongyloides stercoralis (S. stercoralis) infection rate in Okinawa Prefecture was less than 2% by the traditional method, it has been proven to be 6.2% by the new technique--agar plate method. Thiabendazole has strong activity to eradicate the organism, but it is well known that the rate of severe side effects is extremely high. Therefore, we attempted to evaluate the new treatment for the infection by mebendazole and its combination with thiabendazole. The reason for use of the drug is based on the reports of successful treatment of S. stercoralis infection in humans with the mild and infrequent side effects produced by the drug. Thirty three patients were orally given mebendazole 100 mg twice daily for 28 days. Twenty six patients were given thiabendazole 500 mg thrice daily for 5 days and after that, mebendazole 100 mg twice daily for 9 days. This combination therapy was repeated twice. The following results were obtained: 1) Out of a total of 59 patients, the cure rate was 83.3% (20/24) in single use of mebendazole and 100.0% (22/22) in the combination therapy. 2) Constipation (9.1%) and headache (9.1%) were of relatively high incidence in the mebendazole group, but they were mild. Nausea (19.2%) and headache (15.4%) were observed in the combination therapy group and the drug was discontinued in 2 patients. 3) The incidence of the elevation of S-GOT, S-GPT was noted in 71.4% (20/28) for the mebendazole group and 52.2% (12/23) for combination therapy group. All 13 patients of the mebendazole group were negative in lymphocyte stimulation test for mebendazole.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of multiple jejunal diverticula with strongyloidiasis and malabsorption syndrome].

We reported multiple jejunal diverticula with strongyloidiasis and malabsorption syndrome. To our knowledge, 140 cases including the present one have been reported in Japan. We reviewed these cases in this report.

[Two case reports of septic shock due to Vibrio vulnificus with liver cirrhosis].

We have recently experienced a case of Vibrio vulnificus septicemia which occurred in a patient with hepatic cirrhosis, and as we were able to give early antibiotic treatment, the patient survived. We would like to report this case here together with another case experienced 2 years ago. Case 1 was a 58-year-old male who was attending our hospital as an outpatient for hepatic cirrhosis. At 5:30 pm on August 8, 1987, he consumed abalone and giant clam and at 9 pm complained of high fever with shaking chills. He was admitted to our department as an emergency case. Cefoperazone was administered resulting in a decline of fever on the following day. During the course of treatment he fell transiently into pre-DIC, but due mainly to the administration of antibiotics his condition was subsided. Case 2 was a 53-year-old male who was under medical care in our hospital for grave hepatic cirrhosis. On October 11, 1985, he consumed sushi and two days later suffered chills and pyrexia. A blood culture revealed Vibrio vulnificus. His condition improved transiently with administration of Cefazolin, but oliguria, hypotension and ascites occurred subsequently, and finally the patient died on the 22nd day.