Prospective follow-up study of hepatitis C virus infection in patients undergoing maintenance haemodialysis: Comparison among haemodialysis units

A prospective follow-up study on hepatitis C virus (HCV) infection was conducted in seven haemodialysis units from April 1990 to March 1995. A total of 634 patients were undergoing maintenance haemodialysis in the seven units. Of those, 302 patients participated in the follow-up study; 179 were initially HCV antibody negative and 123 were initially positive. Nine of the 179 initially negative patients became positive for HCV antibody during the follow-up period. In accordance with the appearance of HCV antibody, indicating new infection of HCV, all nine of these patients were diagnosed with HCV viraemia. As no other routes were apparent, HCV infection in all nine patients was likely due to nosocomial transmission. Prevalence of HCV antibody at the start of follow up was significantly higher ( P < 0.001) in haemodialysis units A-C (37.9%) than in haemodialysis units D-G (17.0%). Incidence of new HCV infection was significantly higher ( P = 0.005) in the former units (2.2% per year) than in the latter (0.2% per year). Ten of the 123 patients who were initially positive for the HCV antibody exhibited a loss of reactivity during the follow-up period; of these 10 patients, nine were negative for HCV-RNA from the start of the study. In conclusion, the incidence of new HCV infection seen in patients undergoing haemodialysis suggests that their risk of acquiring HCV infection is directly related to the prevalence of HCV antibody positive patients being treated in the units.     

Enzymatic Hydrolysis of Zenarestat 1-O-Acylglucuronide

Abstract— Zenarestat, (3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-1-y1) acetic acid, an aldose reductase inhibitor is metabolized mainly to the glucuronide in rat and man. The glucuronide was purified from urine of volunteers after ingestion of zenarestat. The structure of the glucuronide was confirmed by LC-MS and NMR as 1-O-acyl-β-glucuronide. This compound was unstable at physiological pH, being converted to its structural isomers and the aglycone with half-life of 25 min at pH 7·4 and 37°C in aqueous solution. Enzymatic hydrolysis of the glucuronide was studied in urine, blood and tissues. β-Glucuronidase in human urine contributed little to the hydrolysis of the glucuronide, while in rat urine at pH 6, it was degraded by β-glucuronidase and the formation of zenarestat was clearly faster than its formation in buffer at pH 6. In both rat and human blood, these reactions were accelerated by albumin, although rat red blood cells may also contribute. The rate of degradation was not affected by red blood cell membrane, haemoglobin, globulin, esterases or β-glucuronidase. Arylesterase in rat liver, arylesterase and acetylcholinesterase in the kidney, and β-glucuronidase in both tissues may contribute. Thus, enzymatic degradation of zenarestat 1-O-acyl-β-glucuronide is dependent not only on pH and temperature but also on species and the type of tissue or body fluid.     

Pyruvate dehydrogenase complex deficiency with multiple minor anomalies

Pyruvate dehydrogenase complex (PDHC) deficiency is known to cause congenital lactic acidosis. The case of a 9-month-old female infant with PDHC deficiency caused by a mutation in exon 11 of the pyruvate dehydrogenase (PDH) Elα gene is described. Her facial features were as follows: frontal bossing, upslanting palpebral fissures, a short upturned nose, a long philtrum and low set ears. These anomalies are characteristic not only of a malformation syndrome or chromosomal aberration, but also of PDHC deficiency. Because PDHC deficiency requires early treatment, metabolic disorders should be kept in mind in a patient with dysmorphic features. Further, she had multiple minor anomalies including bilateral inguinal herniae, an umbilical hernia and small hands and feet, which have not been described in previous reports.     

Serum Level of Interleukin-4 in Patients with Perennial Allergic Rhinitis During Allergen-Specific Immunotherapy

Interleukin-4 (IL-4) may play a central role in the IgE synthesis system, the development of Th-2-like cells, and co-ordination as well as the persistence of airway inflammatory process in allergic disorders. Therefore, IL-4 plays a key role in airway allergic disorders. This study aimed at investigating the serum concentrations of IL-4 in patients with perennial allergic rhinitis, with special reference to the possible changes and the clinical relevance following long-term immunotherapy. The study has demonstrated that the serum level of IL-4 in allergic rhinitis patients before immunotherapy is significantly higher than that in non-atopic individuals. However, the serum IL-4 level in allergic rhinitis patients did not decrease following anti-allergic medications but significantly decreased following immunotherapy. The percentage decrease in IL-4 was correlated significantly with the percentage decrease in specific IgE antibodies following long-term immunotherapy. Immunotherapy also significantly decreased specific IgE antibodies, but this reduction in specific IgE antibodies was not significantly correlated with the clinical improvement. In contrast, the percentage decrease in serum IL-4 was significantly correlated with the percentage decrease in symptomatic scores. The authors interpret these data to mean that immunotherapy alters T-cell cytokine profiles in the long-term, and a decline of IL-4 following immunotherapy could modulate not only production of specific IgE antibodies but also inflammatory cellular events, leading to symptomatic relief in allergic rhinitis.     

Adenosquamous Cell Carcinoma of the Colon with Severe Hypercalcemia: --Report of Two Cases--

Two patients with adenosquamous cell carcinoma of the colon,who presented severe hypercalcemia, are reported. Adenosquamouscell carcinoma of the colon is relatively rare, and there wereonly two cases among 1,053 patients who were hospitalized withmalignancy in the large intestine at the National Cancer CenterHospital during the past 18 years. Both of these cases presentedlethal hypercalcemia in the absence of osseous metastasis, andthere were no other patients who had malignant tumors of thelarge intestine and presented hypercalcemia. These observationssuggest that there is a close relationship between the squamouscell component and the occurrence of hypercalcemia, as is observedin the case of lung cancer. Radioimmunoactive parathyroid hormonewas undetectable in the plasma and the tumor tissue in thesetwo cases.