Efficacy and safety of the selective oral neuraminidase inhibitor oseltamivir for prophylaxis against influenza--placebo-controlled double-blind multicenter phase III trial

We have investigated the long-term prophylactic efficacy and safety of oseltamivir phosphate (Ro64-0796), an orally bioavailable prodrug of novel, potent and selective type A and type B influenzavirus neuraminidase inhibitor, when Ro64-0796 was administered orally to the healthy volunteers. Participants older than 16 year-old were randomly assigned to either Ro64-0796 75 mg once daily group or matching placebo group for six weeks. A total of 308 participants (Placebo group; 153 and Ro64-0796 group; 155) were enrolled in this trial. The primary variable of efficacy, incidence of laboratory-confirmed influenzavirus infected subjects accompanied by both fever of 37.5 degrees C or higher and at least two influenza symptoms (group 1) were 1.3% in Ro64-0796 group in contrast with 8.5% in placebo group, inducing 85% inhibition of infection (p = 0.00323, Fisher's exact test). As secondary variable, incidence of laboratory-confirmed influenzavirus infected subjects who lack either fever (37.5 degrees C or higher) or at least two influenza symptoms (group 2) and incidence of asymptomatic infected subjects (group 3) were tend to decrease in Ro64-0796 group, and finally cumulative inhibition rate was 76% in group 1 + 2 combined (p = 0.000891. Fisher's exact test), and 63% in group 1 + 2 + 3 combined (p = 0.002150, Fisher's exact test). As for the safety evaluations, Ro64-0796 was well tolerated but was associated with gastrointestinal disorders such as nausea and vomiting which were mild and allowable for the clinical use. There was no abnormal change attributable to Ro64-0796 application in the clinical laboratory tests as well as the physiological tests. Our results demonstrate that oseltamivir is safe and effective for the prevention of influenza.     

Acute right-sided hemorrhagic colitis associated with oral administration of ampicillin

Among 56 cases who presented to Kanto-Teishin Hospital complaining of bloody diarrhea or considerable hematochezia of acute onset, 8 cases (14.3%) were considered due to colitis associated with oral ampicillin therapy. The bloody diarrhea, often with abdominal cramps, began 2–7 days after starting the treatment. The dosage of ampicillin taken ranged from 2.0 to 4.5 g. Early total colonoscopy and biopsy revealed marked mucosal hemorrhage with minimal or no inflammatory changes mainly in the right colon. Rectum and sigmoid colon are completely normal except in one case. Symptoms rapidly resolved after the endoscopy. At follow-up colonoscopy, performed 4–12 days later, the mucosal changes had cleared completely. There was no evidence to support a hypersensitivity reaction of the colonic mucosa to ampicillin. We believe that right-sided hemorrhagic colitis is one of the common forms of colitis associated with ampicillin. Its differentiation from other kinds of acute colitis and the importance of early total colonoscopy are discussed.     

Antibiotic-associated segmental hemorrhagic colitis: a case report]

Pseudomembranous colitis is a well known complication of antibiotic therapy. Only recently few cases of another form of an antibiotic-associated colitis, the acute segmental haemorrhagic penicillin-associated colitis, have been described. We report another case and point out the importance of early colonoscopy to distinguish the disease from the pseudomembranous colitis.     

Clinical efficacy and safety of the selective oral neuraminidase inhibitor oseltamivir in treating acute influenza--placebo-controlled double-blind multicenter phase III trial

We conducted the placebo-controlled double-blind multicenter Phase III trial of newly developed selective oral neuraminidase inhibitor, oseltamivir phosphate (Ro64-0796), in order to evaluate the efficacy and safety, when Ro64-0796 was administered orally to both type A and type B influenzavirus infected patients. Patients were randomly assigned to either Ro64-0796 75 mg twice daily group or matching placebo group for five days. A total of 316 patients (Ro64-0796 group; 154 and placebo group; 162) were recruited, and intent-to-treat infected population, which was defined as the patients that study drug was administered one or more and laboratory-confirmed influenzavirus infection was demonstrated, were 122 and 130, respectively. Ro64-0796 decreased significantly median viral titers after 72 hours (p = 0.0009. Analysis of covariance), indicating the rapid inhibition of virus replication, and duration of illness which was primary variable of efficacy, was reduced statistically significant by one day (23.3 hours) (p = 0.0216, generalized Wilcoxon test). Ro64-0796 treatment also resulted in the reduction of the fever duration and severity of clinical symptoms. Concerning the safety evaluation, the main accompanied symptoms with Ro64-0796 application were gastrointestinal disorders such as bellyache, nausea and vomiting. Most of these events were mild and allowable for the clinical use. There was no abnormal change attributable to Ro64-0796 application in the clinical laboratory tests as well as the physiological tests. Our data suggests that Ro64-0796 is useful in treating the acute influenzavirus infection.     

Acute hepatitis induced by HMG-CoA reductase inhibitor,lovastatin

Summary The HMG-CoA reductase inhibitor, lovastatin, is known to induce asymptomatic liver dysfunction in a few patients. We report the case of an adult who suffered from clinical hepatitis three months after the onset of lovastatin administration. Manifestations included asthenia, jaundice, and increased aminotransferase and alkaline phosphatase activities. Histologic examination showed centrilobular necrosis, centrilobular cholestasis, and infiltrates with mononuclear and polymorphonuclear cells, including eosinophils. Withdrawal of lovastatin was followed by complete normalization of liver tests within two months.     

Acute eosinophilic pneumonia induced by cigarette smoking]

The subject was a 24-year-old man who presented with acute fever, dry cough, and dyspnea. Chest X-ray films revealed diffuse infiltrates in both lungs. Bronchoalveolar lavage fluid specimens contained an increased number of eosinophils. Transbronchial lung biopsy specimens demonstrated the infiltration of eosinophils into alveolar walls and air spaces. These findings were consistent with acute eosinophilic pneumonia. The patient recovered without medical treatment. Eight days prior to admission, he had resumed smoking after 3 years of abstention. It was suggested that the cause of acute eosinophilic pneumonia in this case was associated with the resumption of smoking. To confirm that association, a smoking challenge test is usually necessary. However, similar symptoms also developed later, after the patient was passively exposed to cigarette smoke. Therefore, we concluded that smoking was probably the etiologic agent of his illness.