A case of erythropoietic protoporphyria with liver cirrhosis suggesting a therapeutic value of supplementation with alpha-tocopherol.

Erythropoietic protoporphyria (EPP) was diagnosed in a 27-year-old man based on a typical clinical history, and a marked increase in erythrocyte and fecal protoporphyrin concentrations. Although liver disease is not a common feature in EPP, he had slight liver dysfunction. A percutaneous liver biopsy was performed and it showed minimal hepatocellular damage and many reddish brown pigment deposits in hepatocytes, Kupffer cells, portal histiocytes, bile canaliculi and small biliary radicles. Electron microscopic findings confirmed that these deposits were composed of protoporphyrin crystals. Liver biochemistry remained well for >2 years, but deteriorated rapidly and second liver biopsy obtained 28 months after the first biopsy revealed the development of liver cirrhosis. We treated the patient with intravenous administration of dl-a-tocopherol acetate (vitamin E; 500 IU/body/day). Following the administration of vitamin E, the concentration of protoporphyrin in erythrocytes decreased significantly and the liver function tests were improved. Sixteen weeks later he showed the full clinical and biochemical recovery suggesting that vitamin E supplementation might be useful in treating patients with EPP who developed liver damage.

An ultrastructural study of the liver in erythropoietic protoporphyria.

An ultrastructural investigation of the liver was performed in two patients with erythropoietic protoporphyria. There were many protoporphyrin crystals in the hepatocytes, Kupffer cells, bile canaliculi, epithelia of bile ducts, and sinusoidal endothelial cells and also free within sinusoids. In hepatocytes, these deposits were composed of granular amorphous materials and numerous slender, straight, or slightly curved needle-like crystals aligned in radial orientation. They were randomly distributed in the cytoplasm and completely replaced other cytoplasmic structures. Some crystals lay free in the cytoplasm and others were surrounded by a single membrane. In the bile canaliculi, severe alterations could be observed. Some of the bile canaliculi were filled with amorphous, noncrystalline pigments, and lumina were enlarged with loss of micro-villi. In addition, despite the absence of protoporphyrin deposits, there were many dilated bile canaliculi. The microfilamentous network around such dilated bile canaliculi was no longer evident, suggesting the depolymerization of actin filaments, which could lead to bile excretory disturbances. The bile duct epithelia showed focal apical membrane bleb formation. The functional or structural alterations of the sinusoidal endothelial cells by the protoporphyrin crystals might lead to the hepatic disturbances. These ultrastructural findings of the liver might contribute to the understanding of the pathogenesis of complicated liver disease in erythropoietic protoporphyria.

[Clinical study of prulifloxacin on infectious enteritis. Japan Research Committee of Prulifloxacin, Research Group on Infectious Enteritis].

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.

Predicting the need for hospital admission in patients with acute bronchial asthma.

Historical data, physical findings, pulmonary function, arterial blood gases, and subjective degree of dyspnea rated on a modified Borg scale were correlated with eventual requirement of hospitalization in 83 episodes of acute asthma attacks of 70 adult patients. Among the pretreatment data, only pulse rate remained significant by a multivariate analysis to predict hospitalization. For patients who had apparently been successfully treated in the emergency room and discharged home, residual degree of subjective dyspnea was the only significant variable chosen by a linear discriminant function to predict the eventual need for hospitalization, with a sensitivity of 75% and a specificity of 78%. We concluded that careful clinical evaluation still remains the best available diagnostic tool in the care of acute asthma.

Dyspnea in acute bronchial asthma in an emergency room.

Pulmonary function, arterial blood gases, and pulse rate were prospectively compared with dyspnea perceived by patients before and after emergency room treatment for acute asthma in 83 episodes. Subjective degree of dyspnea was rated on a modified Borg scale. Before treatment, all spirometry (FVC, FEV1, and peak expiratory flow rate) and arterial blood gas (PaO2, PaCO2, and bicarbonate) data as well as pulse rate were significantly correlated with modified Borg scale, but only PaCO2 showed significant correlation (P < .001) in a multivariate analysis. After treatment, only PaO2 was significantly correlated with modified Borg scale (P = .008) in a multivariate analysis, and pulse rate showed correlation of borderline significance (P = .06). In another 37 episodes of relapsed acute asthma, the correlations between laboratory data and modified Borg scale were very weak, especially after treatment. We conclude that dyspnea expressed by asthmatic patients in an emergency room might be reflecting different mechanisms as treatment is performed. Although it should be one useful guide in emergency evaluation, it must be recognized that dyspnea in the same patient could mean different abnormalities.

Clinical features to predict hypoxia and/or hypercapnia in acute asthma attacks.

Arterial blood gas data were correlated with clinical variables including patients' perception of dyspnea and spirometry in 79 episodes of acute asthma attacks. Among several variables that showed univariate significance with severity, only subjective degree of dyspnea rated on a modified Borg scale (MBS) remained predictive to discriminate the presence or absence of hypoxia/hypercapnia in multivariate analyses. MBS alone could predict the arterial blood gas status with accuracy of approximately 75%. Therefore, patients' sensation of dyspnea seemed to be an important factor in the evaluation of acute asthma in an emergency room.